Cerebral Syndrome Research Articles

Continuous age- and sex-adjusted reference intervals of urinary markers for cerebral creatine deficiency syndromes: a novel approach to the definition of reference intervals.

Urinary concentrations of creatine and guanidinoacetic acid divided by creatinine are informative markers for cerebral creatine deficiency syndromes (CDSs). The renal excretion of these substances varies substantially with age and sex, challenging the sensitivity and specificity of postanalytical interpretation. Results from 155 patients with CDS and 12 507 reference individuals were contributed by 5 diagnostic laboratories. They were binned into 104 adjacent age intervals and renormalized with Box-Cox transforms (Ξ). Estimates for central tendency (μ) and dispersion (σ) of Ξ were obtained for each bin. Polynomial regression analysis was used to establish the age dependence of both μ[log(age)] and σ[log(age)]. The regression residuals were then calculated as z-scores = {Ξ - μ[log(age)]}/σ[log(age)]. The process was iterated until all z-scores outside Tukey fences ±3.372 were identified and removed. Continuous percentile charts were then calculated and plotted by retransformation. Statistically significant and biologically relevant subgroups of z-scores were identified. Significantly higher marker values were seen in females than males, necessitating separate reference intervals in both adolescents and adults. Comparison between our reconstructed reference percentiles and current standard age-matched reference intervals highlights an underlying risk of false-positive and false-negative events at certain ages. Disease markers depending strongly on covariates such as age and sex require large numbers of reference individuals to establish peripheral percentiles with sufficient precision. This is feasible only through collaborative data sharing and the use of appropriate statistical methods. Broad application of this approach can be implemented through freely available Web-based software.

High Altitude

People have been visiting or living in the highest mountain ranges on earth throughout history. However, the hypoxic conditions at these altitudes create a challenge for the human body. The documented success of reaching the summit of Mount Everest without oxygen shows the enormous ability of the human body to adapt to these extreme conditions. Surviving in this low oxygen tension environment requires an amazing expansion of the capacity of various body systems involved in the oxygen pathway and challenges their integrative work. Sometimes, however, the adaptation mechanisms may cause unique illnesses related to high altitude. Cerebral syndromes of acute mountain sickness and high-altitude cerebral edema, and the pulmonary syndrome of high-altitude pulmonary edema, characterize the illnesses in new arrivals to high altitude; whereas chronic mountain sickness occurs in inhabitants of the highest altitude settlements. Children experience the full range of high-altitude–associated illnesses but also have their unique health issues. Symptomatic high-altitude pulmonary hypertension is a unique illness seen mostly in infants. Low birth weight, growth problems, and nutrient deficiency have been documented in children who are born and live in high altitude. Investigation of human physiology in extreme environmental conditions like high-altitude may also contribute to understanding other similar pathologies, and may help develop successful treatments for these diseases. In this review, we discuss the physiology and pathophysiology of ascent to high altitudes and discuss the adaptation processes of permanent residents at these heights in both adults and children.

Hyponatremia in the neurocritical care patient: An approach based on current evidence

In the neurocritical care setting, hyponatremia is the commonest electrolyte disorder, which is associated with significant morbimortality. Cerebral salt wasting and syndrome of inappropriate antidiuretic hormone have been classically described as the 2 most frequent entities responsible of hyponatremia in neurocritical care patients. Nevertheless, to distinguish between both syndromes is usually difficult and useless as volume status is difficult to be determined, underlying pathophysiological mechanisms are still not fully understood, fluid restriction is usually contraindicated in these patients, and the first option in the therapeutic strategy is always the same: 3% hypertonic saline solution. Therefore, we definitively agree with the current concept of “cerebral salt wasting”, which means that whatever is the etiology of hyponatremia, initially in neurocritical care patients the treatment will be the same: hypertonic saline solution.

Mild guanidinoacetate increase under partial guanidinoacetate methyltransferase deficiency strongly affects brain cell development

Among cerebral creatine deficiency syndromes, guanidinoacetate methyltransferase (GAMT) deficiency can present the most severe symptoms, and is characterized by neurocognitive dysfunction due to creatine deficiency and accumulation of guanidinoacetate in the brain. So far, every patient was found with negligible GAMT activity. However, GAMT deficiency is thought under-diagnosed, in particular due to unforeseen mutations allowing sufficient residual activity avoiding creatine deficiency, but enough guanidinoacetate accumulation to be toxic. With poorly known GAA-specific neuropathological mechanisms, we developed an RNAi-induced partial GAMT deficiency in organotypic rat brain cell cultures. As expected, the 85% decrease of GAMT protein was insufficient to cause creatine deficiency, but generated guanidinoacetate accumulation causing axonal hypersprouting and decrease in natural apoptosis, followed by induction of non-apoptotic cell death. Specific guanidinoacetate-induced effects were completely prevented by creatine co-treatment. We show that guanidinoacetate accumulation without creatine deficiency is sufficient to affect CNS development, and suggest that additional partial GAMT deficiencies, which may not show the classical brain creatine deficiency, may be discovered through guanidinoacetate measurement.

Персонифицированная оценка риска развития неблагоприятных сердечно-сосудистых проявлений у пациентов молодого возраста с дисплазией соединительной ткани

Adverse cardiovascular manifestations (ACVM) were registered during 7-year follow-up of young patients with undifferentiated connective tissue dysplasia (CTD). ACVM developed in 28.42% of patients. Most frequent ACVMs were extension/aneurysm of the thoracic aorta (10.75%), cerebral vascular syndrome (10.56%), and arrhythmias (9.11%). Most significant risk factors for extension/aneurysm of the aorta were pathology of vertebral arteries, common risk factors (arterial hypertension, alcohol/drugs, smoking, heavy physical work, sports activities), bicuspid aortic valve); for pathology of cerebral vessels--completely open Willis' Circle, pathology of vertebral arteries, CTD related changes of skin and spine, diagnostic CTD coefficient > 23, chronic diseases of veins; clinically significant cardiac rhythm disturbances--combined valve manifestations of CTD, myxomatous degeneration of heart valves, pathology of the aorta, male sex, metabolic changes of the myocardium, deviations of circadian index, predominance of sympathetic tone, and diastolic dysfunction. Analysis of clinical characteristics (age, symptoms and severity of CTD, QTc dispersion ≥ 50 ms) and presence of unfavorable genetic polymorphisms in β1-adrenergic receptor gene (Ser49Gly, rs1801252), transcription factor Sp4 gene (A80807T, rs1011168), genes of matrix metalloproteinases type 3 (5A/6A) and type 9 (8202 A/G) allowed to evaluate overall risk of ACVM.

Hiponatremias en el paciente neurocrítico: enfoque terapéutico basado en la evidencia actual

In the neurocritical care setting, hyponatremia is the commonest electrolyte disorder, which is associated with significant morbimortality. Cerebral salt wasting and syndrome of inappropriate antidiuretic hormone have been classically described as the 2 most frequent entities responsible of hyponatremia in neurocritical care patients. Nevertheless, to distinguish between both syndromes is usually difficult and useless as volume status is difficult to be determined, underlying pathophysiological mechanisms are still not fully understood, fluid restriction is usually contraindicated in these patients, and the first option in the therapeutic strategy is always the same: 3% hypertonic saline solution. Therefore, we definitively agree with the current concept of “cerebral salt wasting”, which means that whatever is the etiology of hyponatremia, initially in neurocritical care patients the treatment will be the same: hypertonic saline solution.

Posterior Cortical Atrophy with Acute Onset and Rapid Progressive Visual Symptoms: A Case Report

Posterior cortical atrophy (PCA) is a rare degenerative disease with unknown cause. In 1988, Benson et al.1 reported some patients whose cerebral images showed significant atrophy of the parieto-occipital region with progressive dementia and cortical visual dysfunction. They named this disease as PCA based on image findings. Since PCA is most often associated with the pathological findings of Alzheimer’s disease (AD), some people consider PCA as a visual variant of AD. Because PCA invades the posterior cerebral cortex, Gerstmann syndrome, Balint syndrome, and trans-cortical sensory aphasia may occur along with visual agnosia that occurs relatively early.2,3 Here we report a patient who visited our hospital with complaints of only visual symptom that rapidly progressed. We diagnosed it as PCA through clinical findings, image examinations, and other evidences. CASE REPORT

Frequency of Hyponatremia in Central Nervous System Infections

Central nervous system infections (CNS) limited to the meninges or with brain parenchyma involvement are common causes of hospital admissions. Sodium disorders are associated with considerable morbidity and mortality. Hyponatremia is a common electrolyte disturbance and is a common finding in patients with acute cerebral insult. Current study is plan to ascertain the frequency of hyponatremia in CNS infections, to identify regular screening, as CNS infection, treatment and management is emerging as a great challenge especially in the setting of hyponatremia and its complication. In this study our aim was to determine the frequency of hyponatremia in patients with CNS infections attending tertiary health care hospital. This study was conducted in Jinnah Postgraduate Medical Centre (JPMC), Karachi, Pakistan from 6th May 2014 to 6th November 2014. Total duration of this study was six months. It was a cross sectional study and a total of 192 patients with CNS infections presenting to Hospital were included in this study. Brief history and physical examination was done. Blood sample was collected in a sterile manner for serum sodium levels and was sent to lab. Serum sodium level <130 mmol/L was considered as Hyponatremia. The findings of variables were entered in proforma. Our results showed that the average age of the patients was 43.41 ± 13.64 years. Frequency of hyponatremia in patients with CNS infections was observed in 42.71% (82/192) patients. Frequency of hyponatremia was significant among different age groups, while frequency of hyponatremia was not significant between gender and difference duration of disease Sodium disturbance is serious co morbidity in the neurosurgical population. Physicians should focus on the volume status of hyponatremic patients with neurologic disease to differentiate between Cerebral Salt Wasting (CSW) & Syndrome of Inappropriate Anti Diuretic Hormone (SIADH), because the treatment of the two conditions differs. Healthcare providers should recognize the significance of sodium dysregulation among this population and distinguish between the various therapeutic options in order to advocate safe and effective therapy.

Diagnostic methods and recommendations for the cerebral creatine deficiency syndromes.

Primary care pediatricians and a variety of specialist physicians strive to define an accurate diagnosis for children presenting with impairment of expressive speech and delay in achieving developmental milestones. Within the past two decades, a group of disorders featuring this presentation have been identified as cerebral creatine deficiency syndromes (CCDS). Patients with these disorders were initially discerned using proton magnetic resonance spectroscopy of the brain within a magnetic resonance imaging (MRI) examination. The objective of this review is to provide the clinician with an overview of the current information available on identifying and treating these conditions. We explain the salient features of creatine metabolism, synthesis, and transport required for normal development. We propose diagnostic approaches for confirming a CCDS diagnosis. Finally, we describe treatment approaches for managing patients with these conditions.

Diagnostic criteria of the state of the distributed brain stem regulatory structures in cerebrovascular diseases.

The clinical-neurophysiological study of 62 patients with history of subtentorial ischemic stroke was carried out in order to determine the criteria of dysfunction of morphologically distributed stem regulatory structures. It was revealed that these disorders are sustainable with the possibility of recourse and influence on the course of stroke. It was marked the influence of this disorders on the levels of consciousness, severity of state, recovery rate, asthenia level, sleep function. Manifestations of cerebral cardiac syndrome, impaired attention, orientation reaction, speed of sensomotoric acts are also marked. Patients with these disorders have low rates of recovery of functions. Neurophysiological criteria of these disorders are the lack of expressive reactions in electro­ence­pha­lography, reduction of their overall level, instability of rhythm - generating structures and others.

PT-03 * PROLONGED VASOSPASM FOLLOWING POSTERIOR FOSSA TUMOR RESECTION- A CASE REPORT

Cerebral Vasospasm Syndrome after tumor resection has not been well described in the pediatric population. It is a frequent complication after subarachnoid hemorrhage in adults and few case reports have discussed it following resection of pituitary/sellar tumors. There are only 3 reported pediatric cases in the literature. Usual onset of symptoms occurs at a mean of 8 days postoperatively involving mainly the anterior circulation. We report our experience of a 17-year-old boy who developed recurrent diffuse cerebral vasospasm that lasted 6 weeks after surgery. The patient was diagnosed with a left cerebellar grade IV medulloblastoma and underwent subtotal resection with no major operative complications. 2 weeks after surgery, he developed worsening of focal weakness and expressive aphasia that progressed to lethargy, bradycardia and decreased brainstem reflexes. Magnetic resonance imaging (MRI) showed acute ischemia in the frontoparietal, right occipital, and right medial temporal lobe. Subsequent magnetic resonance angiography two days later showed narrowing of left internal carotid and basilar artery with beading. The spasm progressed the following day to involve the Circle of Willis territories bilaterally. An external ventricular drain was placed and steroids, triple therapeutic hypervolemia, hypertension, and hemodilution therapy, and intrathecal nicardipine were started. His vasospasm improved 10 days later but he developed posterior reversible encephalopathy syndrome secondary to the treatment. As he was weaned off therapy, he became symptomatic again and was found to have a recurrence of vasospasm. His symptoms and MRI vasospasm gradually resolved and at 8 weeks after surgery he was discharged with stable initial postoperative deficits. This is one of the first pediatric cases to describe vasospasm lasting 6 weeks following a posterior fossa tumor resection. The prolonged course of this patient's symptoms shows the importance of early recognition with a high index of suspicion and aggressive treatment of vasospasm in the initial phase.

α+Thalassemia Antagonizes the Malaria-protective Effects of Sickle-Cell Trait

α+Thalassemia Antagonizes the Malaria-protective Effects of Sickle-Cell Trait

RNA sequencing of creatine transporter (SLC6A8) deficient fibroblasts reveals impairment of the extracellular matrix.

Creatine transporter (SLC6A8) deficiency is the most common cause of cerebral creatine syndromes, and is characterized by depletion of creatine in the brain. Manifestations of this X-linked disorder include intellectual disability, speech/language impairment, behavior abnormalities, and seizures. At the moment, no effective treatment is available. In order to investigate the molecular pathophysiology of this disorder, we performed RNA sequencing on fibroblasts derived from patients. The transcriptomes of fibroblast cells from eight unrelated individuals with SLC6A8 deficiency and three wild-type controls were sequenced. SLC6A8 mutations with different effects on the protein product resulted in different gene expression profiles. Differential gene expression analysis followed by gene ontology term enrichment analysis revealed that especially the expression of genes encoding components of the extracellular matrix and cytoskeleton are altered in SLC6A8 deficiency, such as collagens, keratins, integrins, and cadherins. This suggests an important novel role for creatine in the structural development and maintenance of cells. It is likely that the (extracellular) structure of brain cells is also impaired in SLC6A8-deficient patients, and future studies are necessary to confirm this and to reveal the true functions of creatine in the brain.

Operative techniques in patients with type A dissection complicated by cerebral malperfusion.

Early mortality and morbidity after surgical treatment for acute type A aortic dissection (AAAD) has remained high over the last decades despite technical improvements and is still in the range of 10–30% [1–6]. The most important risk factor for this still high early mortality is the preoperative status of the patients [4, 7]. Especially end-organ malperfusion contributes significantly to perioperative death and is present in approximately one-third of all patients with acute aortic dissection [3, 7–9]. Coronary, cerebral, visceral and lower extremity malperfusion syndromes are most often associated with type A dissection. A significant surgical dilemma is the treatment of AAAD patients with preoperative cerebral malperfusion [7]. Intimal tears in the proximal aorta often up to 37% [10] result in the involvement of the supra-aortic branches. Consequently, the impaired flow in the brainsupplying arteries is, besides coronary arteries, the most frequent form of malperfusion [7]. The reported incidence of neurological deficit before surgery in AAAD varies between 14% [7] and 20% [11]. The general surgical strategy in AAAD patients is directed towards (i) cannulation and perfusion of the true lumen, (ii) perfusion of all body regions intraoperatively, (iii) a certain degree of hypothermia, (iv) avoiding aortic cross-clamp during distal repair (open distal anastomosis), (v) avoiding changing arterial cannulation site and uncertain de-airing manoeuvres when resuming total body perfusion after distal aortic repair and (vi) unrestricted global perfusion postoperatively. To develop an individual surgical plan for those patients with supra-aortic malperfusion, preoperative assessment of the extent of dissection and type of malperfusion is of utmost importance. This assessment is usually done with computed tomography angiography (CTA) preoperatively, which translates to only a few minutes of delay on the way to the operating theatre and is just as important for the surgical outcome as surgical experience [6, 12]. Malperfusion can be further validated intraoperatively by using transoesophageal echocardiography (TEE), orbital Doppler and near-infrared spectroscopy (NIRS) [9]. One has to keep in mind, however, that NIRS does not provide information in the basilar artery region [9]. There is an ongoing debate about the best surgical strategy for AAAD in general and even more for the high-risk subgroup of patients with cerebral malperfusion [9]. Despite a consensus that the true lumen of the arterial system should be cannulated [13], the approaches vary considerably. This lack of evidence to enable any recommendations for the choice of surgical methods is related to the fact that randomized studies in AAAD (with wide variations of pathologies) are very unlikely to be performed. Even though a meta-analysis of 14 papers between axillary artery and femoral artery perfusion has shown that axillary arterial perfusion had a significantly lower complication rate [14], routes that are currently advocated for AAAD include subclavian (right and left) cannulation, common carotid artery (right and left) cannulation [15, 16], cannulation of the innominate artery, peripheral cannulation of a non-dissected artery (femoral), ascending aortic cannulation (Fig. 1) [17] or apex of the left ventricle (transapical). There is also no agreement about optimal protection (e.g. temperature) during circulatory arrest; however, even the best method of protection would be useless if the cerebral perfusion and other end-organ perfusion have not been restored during cardiopulmonary bypass (CPB) and aortic repair. In this ‘Great Debate’, different approaches are being described and the rationale for doing so is explained by world-known experts in this field. Special emphasis will be placed on common carotid, subclavian and innominate artery cannulation for antegrade cerebral perfusion (ACP). The rationale of retrograde cerebral perfusion (RCP) during selective cerebral perfusion is also described.

Dental Treatment of Pediatric Patients under General Anesthesia at Prince Rashid Bin Al-Hassan Hospital : A Retrospective Study

Objectives: The aim of this study was to evaluate the indications, characteristics of patients, and modalities of dental treatment of pediatric patients under general anesthesia at Prince Rashid military hospital in Irbid. Methods: This was a hospital- based, non- comparative, retrospective study, conducted at Prince Rashid Bin Al-Hassan military hospital in the North of Jordan over a period of 7 years between January 2006 and February 2013. Medical records of all pediatric patients who were treated under general anaesthesia were included. Extracted data included: age, gender, indication for treatment, type of treatment and procedure(s), number of teeth treated, number of previous dental treatment under general anesthesia, general health status, outcome, and follow up period. All patients were preoperatively assessed for general anaesthesia fitness by a pediatrician. Results: A total of 265 patients had dental treatment under general anesthesia, 144 (54.3%) males and 121 (45.7%) females with a male to female ratio of 1.2: 1 in both groups. The healthy patients were 226 (85.3%), 118 males and 108 females (male: female 1.1:1) and the disabled patients were 39 (14.7%), 28 males and 11 females (male: female 2.5: 1). The mean age of the patients was 5.98 years with a range of 2.5 to 15 years. The commonest age group treated was 4 to 6 years and the least common was 13-18 years in both healthy and disabled patients. The main indication for treatment of disabled and healthy patients was extreme un-cooperation. The commonest dental treatment provided for healthy male patients was dental extraction and for healthy female patients was dental fillings, while in disabled patients it was dental extraction for both male and female patients. The majority of patients were treated once under general anesthesia although percentage of disabled patients treated more than one time under general anesthesia was slightly higher than healthy patients. The main cause of medical or mental disability was cerebral palsy and rare syndromes such as De Lange, Ellis Van Crevelled, Cockayne, and Sanjad Sakati. Follow up period ranged between 6 months and 7 years with an average of 2.8 years. Conclusion: Although dental treatment under general anesthesia is effective and has the privilege of comprehensive treatment being done in one visit, risks of general anesthesia pose limitations for its use. The main indication for treatment was extremely uncooperative children with extensive dental damage. The commonest dental treatment provided was extraction and rare syndromes were more frequently seen than previous reports.

Continuous vs. blocks of physiotherapy for motor development in children with cerebral palsy and similar syndromes: A prospective randomized study

Objective: To determine whether physiotherapy is more effective when applied in blocks or continuously in children with cerebral palsy (CP). Methods: A prospective randomized cross-over design study compared the effect of regular physiotherapy (baseline) with blocks of physiotherapy alternating with no physiotherapy over one year. Thirty-nine institutionalized children with CP and clinically similar syndromes (6–16 years old, Gross Motor Function Classification Scale II–IV) were included. During the first scholastic year, group A received regular physiotherapy, group B blocks of physiotherapy and vice versa in the second year. The Gross Motor Function Measure 66 (GMFM-66) was the outcome measure. Results: Thirteen children in each group completed the study. GMFM-66 improved (p < 0.05) over the study period in both groups in total; changes (p < 0.05) were seen only in dimension D (group B) and E (both groups) during regular therapy. Conclusion: Physiotherapy may be more effective when provided regularly rather than in blocks.

Study on differentially expressed proteins of effect of Kudiezi injection on cerebral cortexin rats with cerebral ischemic stroke and heat toxin syndrome

This study is to investigate the modulation of Kudiezi (KDZ) injection on differential protein expression in cerebral cortex of rats with cerebral ischemic stroke and heat toxin syndrome established by intraperitoneal injection of carrageenan and middle cerebral artery occlusion (MCAO) methods. According to random number table rats were divided into three groups: drug group, model group and sham group. The tripheye tetrazolium chloride (TTC) staining and HE staining were used to observe brain tissue injury of rats. After therapeutic intervention with above drug for seventy-two hours, the level of differential protein expression was analyzed by two-dimensional gel electrophoresis (2-DE). The results show that there are differential protein expressions between cerebral ischemic stroke and heat toxin syndrome rats and sham rats. Furthermore, as a Chinese medicine injection with effect of clearing heat, resolving toxin and dredging collaterals, KDZ injection can decrease alleviate morphological changes of cerebral ischemia, regulate the levels of some differential proteins expression.

К вопросу дифференциации вирусных энцефалитов

Вирусные энцефалиты являются одной из актуальных проблем современной неврологии. У практикующих врачей возникают диагностические затруднения, требующие дифференциации с опухолевым процессом, острыми церебральными сосудистыми синдромами, токсическими энцефалопатиями, психозами. В связи с этим представляют клинический интерес собственные наблюдения сложности дифференциации вирусных энцефалитов и опухолей головного мозга. Представлены 2 наблюдения с диагнозом «вирусный энцефалит». Были проанализированы неврологический статус, КТ головного мозга, ЭЭГ, ЭхоЭГ, исследования глазного дна, клинико-лабораторные исследования, исследования спинномозговой жидкости, данные объективного анамнеза. Приведенные наблюдения отображают разные клинические манифестации герпетических энцефалитов, необходимость глубокого анализа симптомов заболевания, их динамики, результатов параклинического исследования и обязательной дифференциации, прежде всего с процессами сосудистого и опухолевого характера.

Arterial Hypertension and Posterior Reversible Cerebral Edema Syndrome Induced by Risperidone

Posterior reversible cerebral edema syndrome is a generally reversible neurologic condition that is diagnosed based on distinctive clinical and radiologic findings. The condition, which is mostly associated with severe arterial hypertension, has also been reported to be induced by several medications. We made the diagnosis of hypertension with posterior reversible cerebral edema syndrome in a lean 12-year-old girl treated with the second-generation antipsychotic risperidone. We applied the Naranjo Adverse Drug Reaction Probability Scale and the World Health Organization-Uppsala Monitoring Centre system for causality assessment to the present case. Both scales indicated that a relationship to risperidone was likely. Second-generation antipsychotic agents may occasionally induce an increase in blood pressure even in the absence of overweight. Given this possibility, we recommend routine monitoring of blood pressure during therapy with these agents.

Management of the Malignant Middle Cerebral Artery Syndrome

The malignant middle cerebral artery syndrome, characterized by cerebral edema following large anterior circulation ischemic stroke, is a disease entity with high morbidity and mortality that is easy to recognize, but challenging to manage. In this review, we begin by discussing important aspects of the clinical presentation of the syndrome, including risk factors for deterioration. We then discuss medical measures that can be undertaken before symptomatic cerebral edema occurs and then outline both medical and surgical options for subsequent neurologic worsening. Shared decision making with patients' surrogates regarding decompressive craniectomy in the setting of available clinical trial data is addressed. The authors conclude with a brief discussion of promising novel therapies for preventing cerebral edema.