Silvio Bašić

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.

Determination of cortical language dominance using functional transcranial Doppler sonography in left-handers.

OBJECTIVE Verbal analytical functions are primarily related to the left hemisphere in right-handers, but there is yet no agreement about cortical language dominance in left-handers. Also, there are some contradictory reports about sex differences in cortical language lateralization. The aim of this study is to investigate cortical language dominance in left-handers and to explore gender influence on cortical language representation. METHODS We performed functional transcranial Doppler sonography (previous validated for determination of cerebral language lateralization) during a word generation task, measuring changes in mean cerebral blood flow velocity (BFVmean) in both middle cerebral arteries (MCA) in 150 healthy subjects (75 left-handers and 75 right-handers). In left-handers we observed significant increase BFVmean in right MCA in 58 (77.3%) subjects. Bilateral increase was observed in 11 (14.7%) subjects and increase in left MCA in 6 (8%) subjects. In right-handed group 93.3% subjects showed left cortical dominance, while 6.7% showed bilateral language representation. RESULTS Current results showed significant (P<0.0001) right hemispheric language dominance in healthy left-handed subjects. CONCLUSIONS Our results showed significant difference in hemispheric dominance for verbal function between righthanders and lefthanders. Also there is statistically insignificant female gender tendency for bilateral hemispheric language representation in both handedness.

Growth hormone and insulin growth factor-I levels in plasma and cerebrospinal fluid of patients with multiple sclerosis

Multiple sclerosis (MS) has several clinically different forms. Whereas the illness progresses slowly in most of the patients, 10% have an aggressively progressive course with fatal outcome without signs of remyelination capability. The process of remyelination depends on numerous interactive factors, including the presence of various growth factors, the most important of which in the adult is insulin growth factor-I (IGF-I). On the other hand, the most powerful postnatal regulator of IGF-I is growth hormone (GH), which also acts as a neuroprotective and an antiapoptotic agent, and has direct influence on myelination. Levels of these growth factors have never been examined in the cerebrospinal fluid (CSF) of patients with MS. The levels of IGF-I and GH were measured in serum and CSF of 46 MS patients and compared with those of 49 patients with no evidence of demyelinating disease. The only positive finding was a deficiency of GH in the CSF of MS patients. The possible implications of those findings in the etiopathogenesis of MS will be discussed.

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

BackgroundNeuromyelitis 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 PresentationWe 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.ConclusionIn 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.

Povezanost apolipoproteina E ε2 s kasnijim početkom epilepsije temporalnog režnja

The aim of the study was to evaluate the possible association between Apo E polymorphisms and age at seizure onset in patients with non-lesional temporal lobe epilepsy. Eighty patients with non-lesional temporal lobe epilepsy with or without bilateral tonic-clonic propagation were analyzed. Age at seizure onset was defined as age at the first unequivocal seizure (excluding febrile convulsions). ApoE alleles were determined by a procedure where genome DNA was amplified by chain reaction along with polymerase, using the LightCycler kit (Roche) for ApoE mutations on codons 112 and 158. There was a statistically significant difference between the groups of patients with ApoE ε2/3 and ε3/4 genotypes (p=0.03), but not between patients with ApoE, ε2/3 and ε3/3, and those with ApoE ε3/4 and ε3/3. In conclusion, the results of our study suggested positive association of a specific ApoE genotype and onset of non-lesional temporal lobe epilepsy.

Multiple Cystic Brain Metastases From Papillary Thyroid Carcinoma Mimicking Neurocysticercosis

The papillary carcinoma of the thyroid gland is the most common type of tumor of the thyroid gland with good prognosis and low incidence of distant metastasis. The brain metastases of thyroid gland carcinoma are extremely rare. We report a patient with multiple cystic brain lesions and satisfying criteria for diagnosis of neurocysticercosis. Brain biopsy revealed brain metastases from papillary thyroid carcinoma. The tumor originated from mediastinal thyroid tissue. Even in cases when neuroimaging suggests neurocysticercosis with great accuracy, it is important to exclude metastasis. Extensive brain metastases of primary papillary thyroid carcinoma are extremely rare.

Giant cavernoma of the skull and skeletal-extraskeletal angiomatosis associated with paraproteinemia

Skeletal-extraskeletal angiomatosis is defined as a benign vascular proliferation affecting the medullar cavity of the bone and at least one other type of tissue, including skin, subcutaneous tissue, viscera, muscle, or synovium, and which does not spread to avascular tissue such as cartilage. Primary hemangiomas/cavernous hemangiomas (cavernomas) are exceedingly rare in the skull, accounting for 0.2% of all osseous neoplasms and are usually located in frontal and parietal bones. The authors present the case of a 66-year-old man who was admitted with right-side hemiparesis. MRI revealed a destructive bone lesion of the left frontal bone. Digital subtraction angiography of the brain did not reveal pathological vascularization, but a minor submucous hemangioma was seen in the nasal airway. Urine test for Bence-Jones proteins was positive for IgG λ light chain. Bone marrow aspiration and CSF analysis revealed no evidence of systemic myelomatosis suggesting a monoclonal gammopathy of undetermined significance. A highly vascular tumor was surgically removed. The histopathology verified cavernous hemangioma of the skull and the nasal submucous hemangioma. We discuss the diagnostic procedure, possible pathophysiological mechanisms and treatment implementation. It is possible that immunoglobulins from monoclonal gammopathies have an etiologic role in the development of the bone and skin changes in older patients, as an acquired condition, by producing a vascular injury that could lead to the multiple hemangiomas in skeletal-extraskeletal angiomatosis. To prevent misdiagnosis with lesions of other origins, multiple lesions of the head must be resected and histopathologically verified. In conclusion, to the best of our knowledge, this is the first case of giant cavernous hemangioma of the skull associated with paraproteinemia and skeletalextraskeletal angiomatosis limited to the head.