Luciano de Paola

Bone mineral density and serum levels of 25 OH vitamin D in chronic users of antiepileptic drugs

The aim of this cross sectional study was to evaluate bone mineral density (BMD) and serum levels of 25-hydroxy vitamin D (25OHD) in a group of patients taking antiepileptic drugs (AED) for a seizure disorder. Between May-2001 and January-2003, we evaluated 58 patients (40 women/18 men), 34.4+/-6 years old living in Curitiba or in its metropolitan area, on antiepileptic therapy for 2 to 38 years (10 on monotherapy /48 on multiple drugs regime). The group was matched by age, gender, and bone mass index to 29 healthy subjects (20 women/ 9 men); 34.2+/-5.9 years old. Medical history and physical exam were performed on all subjects with particular information sought about fractures and risks factors for osteoporosis. Blood samples were collected for total serum calcium, albumin, phosphorus, creatinine, total alkaline phosphatase, and liver function tests. BMD of the lumbar spine, femur and forearm was determined by dual energy X-ray absorptiometry (DXA, Hologic QDR 1000). Between February and April-2003, other blood samples were collected to measure 25OHD, intact paratohormone (PTH) and calcium. Unemployment and smoking history were more frequent among patients than among controls (p<0.05). Fifteen patients had a fracture history, all of which occurred during a seizure. The BMD of the lumbar spine (0.975+/-0. 13 g/cm2 vs. 1.058+/-0.1 g/cm2; p<0.03) and of the total femur (0.930+/-0.1 g/cm2 vs. 0.988+/-0.12 g/cm2; p<0.02) was lower in patients than in controls. In 63.5% of patients and in 24.1 % of controls a T-score < -1.0 in at least one site was seen. The AED users had higher total alkaline phosphatase and lower 25OHD (p<0.02). No correlations between BMD and 25OHD were found. The use of phenytoin was correlated with a greater incidence of fractures (RR: 2.38). We conclude that patients on chronic use of AED have alterations in bone metabolism characterized in this study by lower BMD of the lumbar spine and total femur and lower serum concentrations of 25OHD.

Spinocerebellar Ataxia Type 10: Frequency of Epilepsy in a Large Sample of Brazilian Patients

Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant disorder caused by an ATTCT repeat intronic expansion in the SCA10 gene. SCA 10 has been reported in Mexican, Brazilian, Argentinean and Venezuelan families. Its phenotype is overall characterized by cerebellar ataxia and epilepsy. Interestingly, Brazilian patients reported so far showed pure cerebellar ataxia, without epilepsy. Here, authors provide a systematic analysis of the presence, frequency and electroencephalographic presentation of epilepsy among 80 SCA10 patients from 10 Brazilian families. Overall, the frequency of epilepsy was considered rare, been found in 3.75 % of the cases while this finding in populations from other geographic areas reaches 60% of SCA10 cases.

Menkes' disease: case report

Menkes disease is a rare neurodegenerative disorder due to an intracellular defect of a copper transport protein. We describe a 7 months male patient who presented with seizures, hypoactivity and absence of visual contact. The investigation disclosed pilli torti and thrycorrexis nodosa in the hair, low serum levels of both copper and ceruloplasmin, brain magnetic resonance study showed atrophy and white matter hypointensities on T1-weighted images, electroencephalogram reveals moderate background activity disorganization and epileptiform activity, and muscle biopsy with type 2 fiber atrophy. The clinical, laboratorial, genetic, muscle biopsy and neurophysiological findings in Menkes disease are discussed.A doenca de Menkes e uma rara desordem neurodegenerativa causada por defeito intracelular na proteina transportadora do cobre. Descrevemos um paciente de 7 meses, masculino, com crises convulsivas, hipoatividade e ausencia de contato visual. A investigacao demonstrou pilli torti e thrycorrexis nodosa; niveis sericos baixos de ceruloplasmina e cobre; RNM de crânio com atrofia e reducao de sinal da substância branca (imagens em T1); eletroencefalograma com moderada desorganizacao da atividade de base e atividade irritativa; e biopsia muscular com atrofia de fibras do tipo 2. As caracteristicas clinicas, laboratoriais, geneticas, biopsia muscular e estudo neurofisiologico na doenca de Menkes sao discutidas.

Bone density and bone turnover markers in patients with epilepsy on chronic antiepileptic drug therapy

In this comparative, cross-sectional study, we evaluated 55 patients with epilepsy on chronic use of antiepileptic drugs (AED); [(38 females and 17 males, 35 +/- 6 years (25 to 47)] and compared to 24 healthy subjects (17 females/7 males). Laboratorial evaluation of bone and mineral metabolism including measurements of bone specific alkaline phosphatase (BALP) and carboxyterminal telopeptide of type I collagen (CTX-I) were performed. Bone mineral density (BMD) was measured by DXA. BALP and CTX-I levels did not differ significantly between the groups. CTX-I levels were significantly higher in patients who were exposed to phenobarbital (P< 0.01) than those who were not. Patients presented BMD of both sites significantly lower than the controls (0.975 +/- 0.13 vs. 1.058 +/- 0.1 g/cm(2); p= 0.03; 0.930 +/- 0.1 vs. 0.988 +/- 0.12 g/cm(2); p= 0.02, respectively). Total hip BMD (0.890 +/- 0.10 vs. 0.970 +/- 0.08 g/cm(2); p< 0.003) and femoral neck (0.830 +/- 0.09 vs. 0.890 +/- 0.09 g/cm(2); p< 0.03) were significantly lower in patients who had been exposed to phenobarbital, in comparison to the non-phenobarbital users. In conclusion, patients on AED demonstrate reduced BMD. Among the AED, phenobarbital seems to be the main mediator of low BMD and increases in CTX-I.

The role of CYP2C9 polymorphisms in phenytoin-related cerebellar atrophy

PURPOSE Phenytoin is known to be able to induce cerebellar atrophy in patients with epilepsy. It is also known that a CYP2C9 mutation (*2 or *3) reduces phenytoin metabolism by 25-50% and can increase the risk of phenytoin-related side effects. We examined the influence of CYP2C9 polymorphisms on total cerebellar volume and cerebellar gray and white matter volumes in patients with epilepsy taking phenytoin. METHODS For the genotyping, 100 adult patients with documented epilepsy who had been taking phenytoin for >1 year were selected. From this group, we randomly selected 19 mutant individuals (MT group; CYP2C9*2 and *3) for a whole-brain volume measurement using MRI and 19 wild-type individuals (group WT; CYP2C9*1) with similar clinical and demographic characteristics to those in the MT group for comparison. Total intracranial volume measurements were used to normalize the acquired volumes, which were separated into gray matter volume, white matter volume, and total volume. RESULTS The MT group exhibited a significant reduction in cerebellar white matter volume (p=0.002) but not in total cerebellar volume. CONCLUSION Our study is the first to report evidence linking CYP2C9 polymorphism and a reduction in cerebellar volume in epileptic users of phenytoin.

Quality of life issues and occupational performance of persons with epilepsy

Epilepsy causes restrictions in the performance of various daily activities. The aiming of this study was to investigate whether these restrictions affect the perceived quality of life. The assessments Quality of Life in Epilepsy-31 (QOLIE-31) and Canadian Occupational Performance Measure (COPM) were applied in a sample that consisted of a single group of 34 subjects with at least two years of uncontrolled seizures. The results indicated that the most affected domains of QOLIE-31 were seizure worry, 29.77 (±21.72), and effects of drugs, 49.75 (±28.58), and for the COPM, the average of performance and satisfaction were respectively 3.10 (±3.07) and 4.45 (±3.29), and performance limitations most frequently cited were maintain employment (18), left home alone (15) and courses (15). The application of the Spearman correlation coefficient showed that the three main performance limitations posed by the COPM, especially regarding the level of satisfaction, influence the perception of quality of life. Thus, occupational performance proves to be an important area of intervention with subjects with epilepsy.

Achados tomográficos em 1000 pacientes consecutivos com antecedentes de crises epilépticas

We analized the cranial computorized tomography scans (CT) of 1000 consecutive patients with the history of seizures. The seizures were classified in generalized tonic-clonic seizures (GS) and partial seizures (PS) on the basis of the clinical semiology, as it was described by the patients and family members. Seizure types were correlated with age group, sex and CT findings. GS were observed in 70.7% of the patients and PS in 29.3 %. An increased incidence of GS was noted among the age groups 0 to 10 yrs (31%) and 11 to 20 yrs (21.8%). For PS the 0 to 10 yrs (24.5 %), 21 to 30 yrs (16.7%) and 31 tp 40 yrs (18.5%) age groups were the most prevalent groups. The CT scan findings for the GS group were the following: normal studies 48.8 % of the patients, calcifications/cysticercosis (14.0%), neurocysticercosis/cysts (9.6 %), hydrocephalus (4.3%), ischemia (4.2 %), non-definite lesions (4.1 %), tumor (2.5%), and others (12.5%). In the PS group we found 37.4% of normal studies, calcifications/cysticercosis (11.2%), neurocysticercosis/cysts (12.2%), tumor (10.5%), ischemia (5.4%), hydrocephalus (3.7%), non-definite lesions (8.1%) and others (11.6%). We emphasize the importance of CT scan imaging in patients presenting with seizures, particularly in the diagnosis of cysticercosis.

Variables associated with co-existing epileptic and psychogenic nonepileptic seizures: a systematic review

PURPOSE Epileptic seizures (ES) have many mimickers, perhaps the most relevant being psychogenic nonepileptic seizures (PNES). The picture is even more challenging when PNES are associated with ES in a given patient. The aim of this research paper was to delineate the demographic, epileptological and psychiatric profile of that specific population. METHODS A systematic review was carried out from 2000 to 2015 for articles in English, French, Italian, Spanish and Portuguese in PUBMED and EMBASE. Cohort or case-control studies reporting prospective or retrospective original data comparing patients with co-existing ES and PNES with those who had PNES only and ES only have been included. In retained studies, the presence of PNES was confirmed by video-electroencephalography (V-EEG). Forty-eight abstracts were identified. RESULTS Nine studies were retained. Most showed that female gender predominated in both groups with PNES. Patients with co-existing ES and PNES take higher number of antiepileptic drugs (AEDs) than PNES alone. Two studies showed association of concomitant ES and PNES with earlier age of seizure onset. Localizing EEG features and ES type were evaluated in only two studies and their association with either group was inconclusive. Somatoform, conversion or cluster B personality disorders were more frequent in subjects with PNES than with ES. DISCUSSION Patients with concomitant ES and PNES are highly heterogeneous, challenging differentiation on clinical grounds. A diagnosis of conversion or somatoform, anxiety disorders, and the use of a higher number of AEDs than psychiatric medications may have an association with co-existing ES and PNES. Further studies are warranted to differentiate patients who only have PNES from those with co-existing ES and PNES.

Cerebellar hemorrhage as a complication of temporal lobectomy for refractory medial temporal epilepsy: report of three cases

Cerebellar hemorrhage is listed among the potential complications following neurosurgical procedures. In this scenario it is usually reported as a rare condition. However, it seems that epilepsy surgery patients are somewhat more prone to this kind of complication, compared to other surgical groups. Head positioning, excessive cerebral spinal fluid draining and the excision of non-expanding encephalic tissue (or combinations among the three) are likely to be cause underlying remote cerebellar hemorrhage. Out of the 118 ATL/AH performed at our institution, between 1996 and 2002, we identified 3 (2.5%) patients presenting with cerebellar hemorrhage. We report on such cases and review the literature on the topic.

Vagus nerve stimulator in patients with epilepsy: indications and recommendations for use

Epilepsy comprises a set of neurologic and systemic disorders characterized by recurrent spontaneous seizures, and is the most frequent chronic neurologic disorder. In patients with medically refractory epilepsy, therapeutic options are limited to ablative brain surgery, trials of experimental antiepileptic drugs, or palliative surgery. Vagal nerve stimulation is an available palliative procedure of which the mechanism of action is not understood, but with established efficacy for medically refractory epilepsy and low incidence of side-effects. In this paper we discuss the recommendations for VNS use as suggested by the Brazilian League of Epilepsy and the Scientific Department of Epilepsy of the Brazilian Academy of Neurology Committee of Neuromodulation.