Expression Pattern of 5-HT (Serotonin) Receptors during Normal Development of the Human Spinal Cord and Ganglia and in Fetus with Cervical Spina Bifida.

The expression of 5-HT (serotonin) receptors (sr) was analyzed in the spinal cord and ganglia of 15 human conceptuses (5-10-weeks), and in the 9-week fetus with spina bifida. We used immunohistochemical method to detect sr-positive, apoptotic (caspase-3) and proliferating (Ki-67) cells, double immunofluorescence for co-localization with protein gene peptide (pgp) 9.5 and GFAP, as well as semiquantification and statistical measurements. Following the neurulation process, moderate (sr1 and sr2) and mild (sr3) expression characterized neuroblasts in the spinal cord and ganglia. During further development, sr1 expression gradually increased in the motoneurons, autonomic and sensory neurons, while sr2 and sr3 increased strongly in floor and roof plates. In the ganglia, sr3 expression increased during limited developmental period, while sr1 and sr2 increased throughout the investigated period. Co-expression of sr/pgp 9.5 characterized developing neurons, while sr/GFAP co-localized in the roof plate. In the spinal cord and ganglia of malformed fetus, weaker sr1 and sr2 and stronger sr3 expression accompanied morphological abnormalities. Anomalous roof plate morphology showed an excess of apoptotic and proliferating cells and increased sr3 expression. Our results indicate a human-species specific sr expression pattern, and the importance of sr1 in neuronal differentiation, and sr2 and sr3 in the control of the roof plate morphogenesis in normal and disturbed development.

Multidisciplinary Approach to Complicated Pregnancy.

A nulliparous pregnant woman in her mid-20s and in the 32nd week of gestation presented to the emergency department with severe headache and vomiting. She had an uneventful medical history; however, the physical examination upon hospital admission revealed a hypertensive emergency, papilledema, and 2+ dipstick proteinuria. Upon establishing the diagnosis of preeclampsia, aggressive therapy with corticosteroids, antihypertensive medication, and seizure prophylaxis was initiated. Hemodynamic stability was achieved within 24 hours and the patient remained in the observation unit located within the gynecology clinic. On the ninth day postadmission, however, her condition abruptly deteriorated and advanced to imminent eclampsia, accompanied by transient vision loss, altered mental status, and acute hypertensive crisis. After the patient underwent successful emergent delivery via caesarean section, a laboratory workup revealed hemolysis, elevated liver enzymes, and low platelet count, suggesting HELLP syndrome, a serious complication of eclampsia. This patient concurrently developed posterior reversible encephalopathy syndrome, which was confirmed by magnetic resonance imaging and acute respiratory distress syndrome (the latter presented with diffuse bilateral infiltrates on x-ray and developing pulmonary edema in the absence of cardiac etiology). Because of these life-threatening dynamics, the patient was transferred to the intensive care unit for further treatment. This case is a rare cascade of life-threatening complications that developed in a patient and required skillful multidisciplinary decision making and experienced management within an acute critical care setting. The final outcome of the treatment and intensive care was successful because both the patient and child survived and had no chronic or debilitating sequelae.

The predictive value of platelet function point-of-care tests for postoperative blood loss and transfusion in routine cardiac surgery: a systematic review.

Excessive bleeding after cardiopulmonary bypass (CPB) operations remains to be a persistent problem and weak platelet function certainly contributes to bleeding diathesis. Antiplatelet therapy (APT) is an integral component of perioperative management in patients undergoing cardiac surgery procedures, both with and without use of CPB. In addition to individual variability in platelet function, different preoperative APT administration/discontinuation management further affects platelet function, which in turn may reflect bleeding tendency. However, the impact of drug-induced platelet inhibition on early postoperative bleeding extent remains difficult to predict. Herein, we reviewed the available evidence on the association between platelet function testing values and the extent of bleeding and transfusion requirements in early perioperative period. Currently, the association between platelet function measured by ex vivo assay and the occurrence of bleeding events remains uncertain. The intent of this review is to provide comprehensive literature insight into published evidence, investigating the possibility of platelet function tests to predict bleeding extent as well as transfusion requirements in cardiac surgery patients.

Bleeding and Thrombotic Events in Patients Undergoing Mechanical Circulatory Support: A Review of Literature.

Bleeding and thrombotic events are among the most common complications detected in patients with mechanical circulatory support (MCS). Herein, we reviewed the available evidence on the prevalence, etiology, and management of bleeding and thrombotic events in patients following MCS procedures, such as implantation of both intra- and paracorporeal devices that generate either pulsatile or nonpulsatile flow. Extracorporeal life support procedures providing support to the failing heart and lungs were also reviewed. Most bleeding and thromboembolic events occur despite appropriate hemostatic and anticoagulation management based on conventional coagulation laboratory parameters. Prevalence of bleeding events in this population ranges between 5 and 81%. Wide range in prevalence of bleeding reported in literature may be explained by different devices with different anticoagulation protocols being used, as well as different definitions of bleeding outcomes. Although bleeding events are more common than thromboembolic events, the consequences of thrombotic events are often detrimental. Management of bleeding events remains challenging and measures to prevent and treat bleeding events are often followed by thromboembolic events. Therefore, a personalized approach based on point-of-care hemostatic tests and adjusted to device type and patient comorbidities is therefore warranted. To provide advanced understanding of hemostatic disturbances during MCS, prospective trials focused on bleeding and thromboembolic events as primary endpoints should be conducted. Better understanding of the underlying pathophysiology and a shift towards a personalized approach based on functional point-of-care hemostatic properties assessment may provide more favorable clinical outcomes. This should, however, be coupled with further technological improvements providing better device surface hemocompatibility as interaction between blood and device surface affects the hemostatic equilibrium.

Morphological manifestations of the Dandy-Walker syndrom in female members of a family.

The Dandy-Walker syndrome (DWS) is a hereditary disorder, appearing somewhat more frequently in women. The most important characteristics of the DWS are the lack of the cerebellar vermis, varying from a partial lack to a complete agenesis, and enlargement of the cerebrospinal spaces, especially in the fourth ventricle. The above mentioned morphological changes clinically manifest in ataxia, increased intracranial pressure and hydrocephalus. Here is presented a family with DWS, where the disease is contracted only by female members, in two generations, whereas no signs of DWS have been noticed in male family members. DWS is clinically manifested from early childhood to middle age, with the morphological changes varying from hypoplastic cerebellar vermis to widening of the brain ventricles and hydrocephalus and arachnoid cyst in the occipital part.

Which theory for the origin of syphilis is true?

INTRODUCTION: There are four theories about the origin of syphilis, of which the mostly represented one is the Columbian theory. This theory suggests that syphilis was brought into Europe in 1493 ad by the ship from Caribbean islands. AIM: The aim of this study is to test all theories on a sample of 403 skeletons: 135 from prehistory, 134 from antique, and 134 from medieval period and new age from the Dalmatia (Croatia). METHODS: All skeletons were examined using standard anthropological methods. Paleopathological analysis was performed on each skeleton as well as additional radiographic method on one isolated skeleton. MAIN OUTCOME MEASURES: Paleopathological changes on skeletal remains connected with treponematosis. RESULTS: Paleopathological analysis revealed one skeleton from the antique period (second to 6th century A.D.) that exhibited skeletal markers similar to those described in one clinical case in which congenital syphilis was confirmed by a Wasserman reaction. Skeletal remains of this person were examined macroscopically and radiographically, and the differential diagnostics eliminated other considered pathologies as well as trauma. CONCLUSIONS: The finding of skeletal markers of syphilis on a skeleton from the antique supports the theory of pre-Columbian syphilis origin.

Role of NMO-IgG in distinguishing the type of optic neuritis.

PURPOSE: To emphasize the importance of neuromyelitis optica (NMO)-immunoglobulin G (IgG) antibodies testing in patients with typical optic neuritis (ON) refractory to steroid treatment. METHODS: Two patients were evaluated with ON refractory to steroid therapy and poor visual acuity; they were tested for NMO-IgG antibodies. RESULTS: Brain magnetic resonance imaging was normal in both patients. The serum and cerebrospinal fluid were positive for NMO-IgG antibodies. Magnetic resonance imaging of the cervical and thoracic spine revealed lesions longer than three vertebral segments and the diagnosis of NMO was confirmed. Treatment with plasma exchange and immunosuppressive therapy resulted in marked improvement of visual acuity. This improvement was sustained. CONCLUSIONS: The testing for NMO-IgG antibodies is important for distinguishing ON in NMO from multiple sclerosis in cases of ON refractory to steroid treatment. These cases suggest that testing for NMO-IgG antibodies should be performed in comparative trials on a larger series.

CT perfusion and noncontrast CT in acute ischemic stroke diagnosing--is there influence on early thrombolytic therapy outcome?

The objective of this study was to compare noncontrast computed tomography (NCCT) and computed tomography perfusion (CTP) in early diagnosis of acute ischemic stroke and to define influence of these diagnostic procedures on early outcome of thrombolytic therapy (TLTH). The study included 45 patients, 35 patients submitted to NCCT and CTP and 10 patients who underwent only NCCT, before CTP was introduced. Based on the National Institute of Health Stroke Scale (NIHSS) score we compared early outcome of patients who received TLTH after NCCT only (group 1) with the early outcome of patients who received TLTH following NCCT and CTP (group 2). Statistically significant difference was found in acute stroke diagnosing between CTP and NCCT (p = 0.002). There were no statistically significant differences in TLTH early outcome between group 1 and group 2. In conclusion, CTP should be done regulary in patients presenting with acute ischemic stroke symptoms. More research needs to be done in defining exact influence of CTP implementation on the TLTH outcome.

[Lumbosacral spine herniation--computed tomography diagnostics]. / Hernije lumbosakralne kraljeznice--analiza temeljem CT dijagnostike.

The aim of this retrospective study was to establish the incidence of particular types of disk radicular conflicts of the lumbar region. The study showed no patient sex or age differences. Disk radicular conflicts were most commonly diagnosed at L5-S1 and L4-L5 levels. Study results pointed to dorsomedial protrusion of the intervertebral disk to be most common in the study region, followed by dorsolateral one, whereas foraminal protrusion of the intervertebral disk was the rarest one. Study results suggested that there was no significant age or sex difference in the incidence of disk radicular conflicts of the lumbar region.

[Sensitivity and specificity of clinical assessment in the diagnosis of acute brain diseases]. / Osjetljivost i specifijnost klinicke procjene u dijagnostici akutnih mozdanih zbivanja.

Acute brain diseases require timely and correct diagnosis. The basic guideline in treating these patients is clinical-neurological assessment. We tested the sensitivity and specificity of clinical assessment of acute brain disease according to definitive diagnosis determined by neuroradiology and computerized tomography (CT). We found a statistically significant correlation between the disease assessment and brain CT in patients with ischemic stroke. In patients with hemorrhagic stroke and brain tumors, the clinical-neurological assessment was found to be of statistically significantly lower sensitivity and specificity. Clinical assessment may produce false-positive and false-negative findings concerning hemorrhagic stroke and brain tumors. Study results indicated brain CT to be an unavoidable diagnostic method, along with clinical assessment of acute brain disorders.

Cell death in developing human spinal cord.

Cell death in the developing human spinal cord was investigated in 5-12 week human conceptuses using immunohistochemical and TUNEL methods. Expression of pro-apoptotic (Fas-receptor, caspase-3) and anti-apoptotic (bcl-2) markers and marker for internucleosomal fragmentation (TUNEL) were analysed in the cranial and caudal parts of the human spinal cord. In early developmental stages (5-6 weeks) of the cranial spinal cord, bcl-2 positive cells were seen in the ventricular zone and in the roof plate, while in the caudal part they were seen surrounding the central lumen. Subsequently, bcl-2 expression appeared in the basal plates of the grey matter and in the spinal ganglia, and from the seventh week on they also appeared in the intermediate horn of the grey matter. In the fetal period, bcl-2 expression appeared in the dorsal horns of the grey matter (9 weeks) but ceased in the ventricular zone (12 weeks) . In the trunk region, TUNEL-positive cells were found in ventricular and mantle zones along the whole length of the spinal cord. Caspase-3 positive cells and Fas-receptor positive cells appeared only in the grey matter of the cranial segments (head and trunk) of the spinal cord, but they were missing in the caudal parts. Caspase-3 dependant pathway, probably activated by Fas-receptor, seems to operate only in the cranial part of the human spinal cord. In the caudal (sacrococcygeal and tail) parts, cells seem to die by caspase-3 independent pathway. The interplay of pro-apoptotic and anti-apoptotic factors may be associated with cranial spinal cord morphogenesis, adjustment of cells number and selective survival of neurons, while in the caudal regions these factors cause massive cell death associated with regression of the caudal spinal cord.

Internal Watershed Infarction as an Imaging and Clinical Challenge: a Case Report.

We presented the case of a patient with internal watershed infarction with a nonspecific clinical presentation including hemiplegia, hemisensory deficit, and speech disturbance. Neuroimaging and ultrasound diagnostic procedure are important tools for diagnosis of these rare ischemic events that count for about 6% of all strokes.  Specific therapy is mandatory for the diagnosis of watershed infarction and different from the therapeutical measures than can be taken for embolic and atherothrombotic strokes. Our patient was a 69-year-old, right-handed Caucasian woman who presented to our facility with acute right side weakness and speech disturbance. He had hypothyroidism, permanent atrial fibrillation, diabetes mellitus and she was hypotensive. She reported dizziness few days before the accident. Imaging studies revealed internal watershed infarction. Therapeutic procedures were taken to restore low cerebral blood flow. Internal watershed infarction is rare (less than 10% of all strokes) but well recognized a clinical feature of stroke. Specific pathophysiology generally is connected with hypoperfusion and hemodynamic mechanisms. Specific therapy is mandatory for these conditions.

CSF tap test - Obsolete or appropriate test for predicting shunt responsiveness? A systemic review.

OBJECTIVES: There is no accurate test for diagnosing normal pressure hydrocephalus or for screening for patients who will benefit from shunt surgery. Additional tests, such as cerebrospinal fluid tap test (CSF-TT), are often used in practice to provide further predictive value in detecting suitable patients for shunting. We performed a systematic review of the literature to evaluate the CSF-TT's effect on the outcome of main symptoms and on validity parameters in screening patients suitable for shunting. METHODS: In February 2015 we searched electronic databases from their inception to the current date, using the following key words: normal pressure hydrocephalus, idiopathic normotensive hydrocephalus, shunt operation, CSF tap test, predictive value, validity. The search retrieved 8 articles explicitly addressing the topic. RESULTS: There was a very high positive predictive value of CSF-TT: 92% (range from 73% to 100%) but a low negative predictive value: 37% (18%-50%). Also, the CSF-TT has high specificity: 75% (33%-100%) but average sensitivity: 58% (26%-87%). The overall accuracy of the test was 62% (45%-83%). CONCLUSIONS: This systematic review did not provide unambiguous validity of the CSF-TT in the screening of patients for shunting. The validity of the CSF-TT is good for patient inclusion for shunting due to the fact that the positive response to the test is very reliable. Unfortunately, the negative response to the test does not reliably make these patients ineligible for shunting. Further studies are needed to improve and standardize the methodology in order to optimize the detection power of the test.

A global amnesia associated with the specific variant of posterior reversible encephalopathy syndrome (PRES) that developed due to severe preeclampsia and malignant hypertension.

A case is reported of a 26-year-old primiparous woman in the 32nd week of gestation who presented to the emergency department with the symptoms of a severe headache, nausea and vomiting. The patient was diagnosed with preeclampsia that later progressed to eclampsia. This state was characterized by a sudden onset of a headache and diplopia that advanced to cortical blindness and precipitated significant alterations in mental status, most notable being global amnesia that resolved within 48 h. A post-partum magnetic resonance imaging of the brain in FLAIR mode revealed multiple cortico-subcortical areas of hyperintense signals suggestive of edematous lesions that chiefly involved occipital and parietal lobes with additional atypical manifestations. Such radiologic findings suggested a posterior reversible encephalopathy syndrome variant with the global amnesia as an extraordinary constituent. This unique feature should be acknowledged when treating a preeclamptic or hypertensive patient that exhibits neurological symptomatology and vision disturbances.