Identification and Validation of Novel Cerebrospinal Fluid Biomarkers for Staging Early Alzheimer's Disease

Ideally, disease modifying therapies for Alzheimer disease (AD) will be applied during the 'preclinical' stage (pathology present with cognition intact) before severe neuronal damage occurs, or upon recognizing very mild cognitive impairment. Developing and judiciously administering such therapies will require biomarker panels to identify early AD pathology, classify disease stage, monitor pathological progression, and predict cognitive decline. To discover such biomarkers, we measured AD-associated changes in the cerebrospinal fluid (CSF) proteome.CSF samples from individuals with mild AD (Clinical Dementia Rating [CDR] 1) (n = 24) and cognitively normal controls (CDR 0) (n = 24) were subjected to two-dimensional difference-in-gel electrophoresis. Within 119 differentially-abundant gel features, mass spectrometry (LC-MS/MS) identified 47 proteins. For validation, eleven proteins were re-evaluated by enzyme-linked immunosorbent assays (ELISA). Six of these assays (NrCAM, YKL-40, chromogranin A, carnosinase I, transthyretin, cystatin C) distinguished CDR 1 and CDR 0 groups and were subsequently applied (with tau, p-tau181 and Aβ42 ELISAs) to a larger independent cohort (n = 292) that included individuals with very mild dementia (CDR 0.5). Receiver-operating characteristic curve analyses using stepwise logistic regression yielded optimal biomarker combinations to distinguish CDR 0 from CDR>0 (tau, YKL-40, NrCAM) and CDR 1 from CDR<1 (tau, chromogranin A, carnosinase I) with areas under the curve of 0.90 (0.85-0.94 95% confidence interval [CI]) and 0.88 (0.81-0.94 CI), respectively.Four novel CSF biomarkers for AD (NrCAM, YKL-40, chromogranin A, carnosinase I) can improve the diagnostic accuracy of Aβ42 and tau. Together, these six markers describe six clinicopathological stages from cognitive normalcy to mild dementia, including stages defined by increased risk of cognitive decline. Such a panel might improve clinical trial efficiency by guiding subject enrollment and monitoring disease progression. Further studies will be required to validate this panel and evaluate its potential for distinguishing AD from other dementing conditions

Posterior fossa arachnoid cysts

Arachnoid cysts of the posterior fossa are rare lesions that are considered to be mostly congenital in origin. In this article, we retrospectively review 12 patients who underwent surgical treatment for their symptomatic posterior fossa arachnoid cysts. The most common presenting symptoms were gait disturbances and headache. The diagnosis was established on computed tomography or magnetic resonance imaging. Surgery consisted of cyst wall excision with fenestration in nine cases and shunting procedures in three cases. In all cases except one who died, the postsurgical follow-up neuroradiological investigations showed that the cysts had decreased in size, the cerebellum had re-expanded, and if there was preoperative hydrocephalus, the ventricular size was decreased. The follow-up period ranged from 1 to 11 years. All surviving cases are free of symptoms and no arachnoid cysts recurred. The classification, pathophysiology; differential diagnosis and surgical treatment of infratentorial arachnoid cysts are discussed and the relevant literature is reviewed

The role of mebendazole in the surgical treatment of central nervous system hydatid disease

Although hydatid disease is the most common human disease caused by helminths, cerebral and spinal involvement in hydatid disease is rare. Recurrence is common when cysts rupture during surgical removal. The authors present the results of combined treatment with surgery and mebendazole in four cerebral and fi ire spinal cases of hydatid disease. The patients' ages ranged between 4 and 55 years with a mean of 26 years. In three of the four cranial patients who received mebendazole treatment, the cysts ruptured during surgical removal. Four of the five spinal cases had recurrent disease at the time of admission. Mebendazole was started immediately after surgery and continued over 12 months. All cases but one ape stable clinically or radiologically at a mean 27 months follow-up period

Chiari type I malformations in adults: a morphometric analysis of the posterior cranial fossa

Objective: Chiari type I malformation (CMI) is a congenital disorder characterized by caudal displacement of the cerebellar tonsils through the foramen magnum into the spinal canal. Recent studies suggest that overcrowding in the posterior cranial fossa (PCF) because of underdeveloped bony structures in the intrauterine life is the main cause of this malformation. For this reason, the authors want to contribute to the current literature, which focuses on bone abnormalities in the PCF in patients with CMIs

Cerebrospinal fluid superoxide dismutase and serum malondialdehyde levels in patients with aneurysmal subarachnoid hemorrhage: preliminary results

Objectives: Experimental studies provide evidence that oxidative damage plays a role in the development of vasospasm after aneurysmal subarachnoid hemorrhage (SAH) but data from human studies is still limited. The purpose of this study was to investigate the time course of cerebrospinal fluid (CSF) superoxide dismutase (SOD) and serum malondialdehyde (MDA) changes in patients with aneurysmal SAH

Iniencephaly: neuroradiological and surgical features - Case report and review of the literature

Iniencephaly is a rare congenital anomaly characterized by spina bifida of the cervical vertebrae, fixed retroflexion of the head on the cervical spine, and occipital bone defect. There are only five reports of surviving patients with iniencephaly. The authors report the case of a newborn who presented with iniencephaly and an encephalocele that were surgically treated in our service. Neurological examination of the patient yielded normal results except for a moderate psychomotor retardation. The neuroradiological and surgical findings of the case suggested that the trigger of the anomaly was the occipital bone defect and rachischisis of the posterior vertebral arches

The effect of intraventricular albumin in experimental brain oedema

Therapy for vasogenic brain oedema (VEE) is still an unsolved problem. Experimental work with the aim of establishing an oncotherapeutic option is presented

Clipping and coiling of intracerebral aneurysms

The purpose of this study was to compare cost-effectiveness between coiling and clipping in patients with ruptured or unruptured cerebral aneurysms during their hospital stay. The authors conducted a retrospective analysis of patients with cerebral aneurysms that were treated by clipping or coiling at Cerrahpasa Medical Faculty Hospital during a 1-year period. Direct hospital-based costs and physicians' fees were calculated and compared between the 2 groups. A total of 76 patients had clipping, and 65 underwent coiling. There were no differences with regard to age or sex in both groups. When comparing major cost categories between the 2 groups, including laboratory tests, medications, blood and blood derivatives, physicians' fees, surgical/embolization supplies, hospital stay, and imaging, a highly statistically significant difference was found in all major cost categories (P < 0.001). The results showed that although coiling allows a shorter hospital stay and results in a low complication rate, the high cost of single-use medical supplies (eg, coil, microcatheters) increased the cost per patient considerably