Clinical and Neurophysiological Changes in Patients with Pineal Region Expansions

In the last 20 years neurological and neurosurgical follow up of our patients with pineal region expansions (118 patients) pointed to certain clinical and neurophysiological regularities. We performed retrospective study which included 84 patients with pineal region expansions in the period from 1992 to 2009. The study included 55 women and 29 men, mean age 30.08±13.93 years, with positive brain magnetic resonance imaging (MRI) – 70 patients (83.4%) had simple pineal gland cysts, and 14 patients (16.67%) had expansive process in pineal region with compressive effect. All patients had headache, while 32 patients (38%) had epileptic phenomena – primary generalized seizures. Patients had common electroencephalography (EEG) pattern with paroxysmal discharges of 3Hz (or more than 3 Hz) spike-and-wave complexes. Operation with supracerebellar infratentorial approach was performed in 70 patients. In most of our patients indication for the operation was established based on the size of the cyst (15 mm or more), with the signs of compression on the quadrigeminal plate and compression of the surrounding veins, which could result in seizures and EEG changes verified in our group of patients. Pathohistological analysis revealed pineocytomas in 11 cases (15.71%), pinealoblastomas in 2 cases (2.86%), one case of teratoma (1.43%), while 56 patients had pineal gland cysts (80%). Following surgery clinical condition improved in all patients – patients became seizure-free and headaches significantly decreased. Other symptoms including diplopiae, nausea, vomiting, vertigo as well as blurred vision also disappeared. There were no complications after surgical procedures. This study points to often appearance of seizures that clinically and neurophysiologically present as primary generalized epilepsy in patients with pineal region expansions. Our hypotheses are that mass effect on the surrounding veins that affects normal perfusion, compressive effect on the quadrigeminal plate and the aqueduct of the midbrain, hemosiderin deposists, as well as secretion disturbances of anticonvulsive agent melatonin can be involved in the pathogenesis of seizures.We suggest to perform high resolution brain MRI with special demonstration of pineal region in all young patients that have seizures and specific EEG changes

Patient with neuromyelitis optica and inflammatory demyelinating lesions comprising whole spinal cord from C2 level till conus: case report

BACKGROUND: Neuromyelitis optica (NMO) is an idiopathic, severe, inflammatory demyelinating disease of the central nervous system, that causes severe optic neuritis and myelitis attacks. Early discrimination between multiple sclerosis (MS) and NMO is important, as optimum treatment for both diseases may differ considerably. ----- CASE PRESENTATION: We report a case of a patient who initially presented as longitudinally extensive transverse myelitis (LETM), having spastic upper extremities diparesis and spastic paraplegia, C2/C3 sensory level and urinary incontinence, as well as extensive inflammatory spinal cord lesions from C2 level to conus. After 5 months the patient had another attack of transverse myelitis, had electrophysiological findings consistent with optic neuritis, was seropositive for NMO-IgG (aquaporin-4 IgG) and thus fulfilled NMO diagnostic criteria. Following treatment of disease attacks with pulse corticosteroid therapy and intravenous immunoglobulins, we included oral azathioprine in a combination with oral prednisone in the therapy. Since there was no significant clinical improvement, we decided to use cyclophosphamide therapy, which resulted in good clinical improvement and gradual decrease of cord swelling. ----- CONCLUSION: In this NMO case report we wanted to emphasize the extensiveness of inflammatory spinal cord changes in our patient, from C2 level to conus. In the conclusion it is important to say that accurate, early diagnosis and distinction from MS is critical to facilitate initiation of immunosuppressive therapy for attack prevention

Patient with neuromyelitis optica and inflammatory demyelinating lesions comprising whole spinal cord from C2 level till conus: case report

Abstract Background Neuromyelitis optica (NMO) is an idiopathic, severe, inflammatory demyelinating disease of the central nervous system, that causes severe optic neuritis and myelitis attacks. Early discrimination between multiple sclerosis (MS) and NMO is important, as optimum treatment for both diseases may differ considerably. Case Presentation We report a case of a patient who initially presented as longitudinally extensive transverse myelitis (LETM), having spastic upper extremities diparesis and spastic paraplegia, C2/C3 sensory level and urinary incontinence, as well as extensive inflammatory spinal cord lesions from C2 level to conus. After 5 months the patient had another attack of transverse myelitis, had electrophysiological findings consistent with optic neuritis, was seropositive for NMO-IgG (aquaporin-4 IgG) and thus fulfilled NMO diagnostic criteria. Following treatment of disease attacks with pulse corticosteroid therapy and intravenous immunoglobulins, we included oral azathioprine in a combination with oral prednisone in the therapy. Since there was no significant clinical improvement, we decided to use cyclophosphamide therapy, which resulted in good clinical improvement and gradual decrease of cord swelling. Conclusion In this NMO case report we wanted to emphasize the extensiveness of inflammatory spinal cord changes in our patient, from C2 level to conus. In the conclusion it is important to say that accurate, early diagnosis and distinction from MS is critical to facilitate initiation of immunosuppressive therapy for attack prevention.</p

The lack of genotype-phenotype relationship between platelet serotonin concentration and serotonin transporter gene promoter polymorphism in healthy subjects

A polymorphism in the serotonin transporter gene (5-HTTLPR) is frequently studied for association with antidepressant treatment response, different personality traits, and psychiatric disorders. Baseline platelet serotonin (5-HT) concentration has been proposed to indicate a good or a poor treatment response to antidepressant drugs and to be associated with particular symptoms in psychiatric disorders. The aim of the study was to elucidate the genotype-phenotype relationship between platelet 5-HT concentration and 5-HTTLPR in healthy subjects. The frequency of 5-HTTLPR genotypes and alleles, as well as platelet 5-HT concentration was evaluated in 434 male and 86 female unrelated healthy medication-free Caucasian subjects of Croatian origin. A two-way ANOVA revealed no significant difference in platelet 5-HT concentration subdivided according to the particular 5-HTTLPR genotype, no significant effect of sex, no significant effect of genotype, and no significant interaction between sex and genotype on platelet 5-HT concentration. In addition, one-way ANOVA did not detect significant effects of homozygous S/S genotype, or homozygous L/L genotype on platelet 5-HT concentration. Our results showed a lack of significant association between platelet 5-HT concentration and 5-HTTLPR variants, suggesting that there is no functional relationship between 5-HTTLPR alleles and platelet 5-HT concentration in the large groups of healthy male and female medication-free Caucasian subjects, free of neuro-psychiatric disorders

Association study of a functional catechol-o-methyltransferase polymorphism and smoking in healthy Caucasian subjects

Tobacco smoking is a global health problem. The association of a functional common polymorphism in the catechol-o-methyltransferase gene (COMT Val158Met) with smoking behavior has been extensively studied, but with divergent findings. In the present study the frequency of COMT genotypes and alleles was evaluated in 578 male and a smaller group of 79 female unrelated, medication-free Caucasian healthy subjects of Croatian origin. Smokers were classified as subjects smoking </=10 cigarettes per day, while subjects who never smoked in their life were regarded as nonsmokers. A chi(2)-test with standardized residuals and Bonferroni correction revealed significant (P=0.017) differences in Met/Met, Met/Val or Val/Val genotype frequency between male smokers and nonsmokers. This significant association between COMT Val158Met polymorphism and smoking was not detected in female subjects, due to the small number of women, which represents a limitation of the study. Our results confirmed the significant association between COMT variants and smoking, which was due to the higher frequency of Val/Val homozygotes in male smokers compared to male nonsmokers. These results suggest that carriers of the high activity COMT variant are more prone to develop a higher level of nicotine dependence, or that they release more dopamine than carriers of Met/Met or Met/Val genotypes

Unraveling the biological mechanisms in Alzheimer's disease - lessons from genomics

Alzheimer's disease (AD) is the most common form of dementia and the most common neurodegenerative disease, with a complex genetic background. Genome-wide association studies (GWAS) have yielded important new insights into genetic mechanisms of AD pathology. Current results unequivocally confirm apolipoprotein E (APOE) as a major genetic risk factor for development of late onset AD. Additional associations of more than twenty genes have also been identified and replicated in subsequent genetic studies. Despite the exciting new GWAS data which have emerged in the last few years, it has become clear that common variants within the genome cannot fully explain the underlying genetic risk for AD. Novel approaches such as genome-wide analysis of copy number variations (CNV) or low-frequency rare functional gene variants may provide additional insight into genetic basis of AD. In this review we summarize the findings of eighteen GWAS studies in AD performed to date, with an emphasis on potential future developments in the quest for genetic risk factors of AD

The influence of C3435T polymorphism of ABCB1 gene on penetration of phenobarbital across the blood-brain barrier in patients with generalized epilepsy

BACKGROUND: Epilepsy is refractory to medical treatment in about one-third of the patients. The exact pathological mechanism of epilepsy pharmacoresistance is still unclear, but a decreased antiepileptic drug (AED) uptake into the brain is suspected to play a role. P-glycoprotein (Pgp), a transmembrane transporter encoded by ABCB1 gene and located at the endothelial cells of the blood-brain barrier (BBB), has been associated with epilepsy pharmacoresistance. ----- OBJECTIVE: To analyze the effect of two ABCB1 gene polymorphisms, C3435T and G2677T/A, on phenobarbital (PB) concentrations in the cerebrospinal fluid (CSF) and serum (S) and to assess the relationship of ABCB1 polymorphisms to phenobarbital penetration across BBB in vivo and seizure frequency. ----- METHODS: CSF PB and S PB concentrations were measured in 60 patients with idiopathic primary generalized epilepsy receiving phenobarbital monotherapy. CSF/S PB concentration ratio was calculated as an index of phenobarbital penetration across BBB. The patients were genotyped for the ABCB1 gene C3435T and G2677T/A polymorphisms. Seizure frequency was recorded during the 6-month phenobarbital monotherapy. ----- RESULTS: Patients with different C3435T polymorphism had significantly different CSF PB concentrations and CSF/S PB concentration ratio. In comparison with CT heterozygotes and TT homozygotes, CC homozygotes had a significantly lower CSF PB concentration (p=0.006) and CSF/PB concentration ratio (p<0.001). G2677T/A polymorphism showed no such effect (p=0.466). CC genotype and low CSF/S PB concentration ratio correlated with increased seizure frequency. ----- CONCLUSIONS: C3435T polymorphism of ABCB1 gene was demonstrated in vivo to significantly influence the CSF/S PB concentration ratio and seizure frequency