Risk factors for suicide in epilepsy: a case control study

PURPOSE: Suicide is considered to be one of the most important causes of death contributing to the increased mortality of persons with epilepsy. We investigated the association between the risk of suicide in persons with epilepsy and clinical factors that might increase or have been suggested to increase the risk of suicide. METHODS: A case-control study was nested within a cohort of 6,880 patients registered in the Stockholm County In-Patient Register with a diagnosis of epilepsy. The study population was followed up through the National Cause of Death Register. Twenty-six cases of suicide, 23 cases of suspected but not proven suicide, and 171 controls, living epilepsy patients, were selected from the cohort. Clinical data were collected through medical record review. RESULTS: There was a ninefold increase in risk of suicide with mental illness and a 10-fold increase in relative risk (RR) with the use of antipsychotic drugs. The estimated RR of suicide was 16.0 [95% confidence interval (CI), 4.4-58.3] for onset of epilepsy at younger than 18 years, compared with onset after 29 years. The risk of suicide seemed to increase with high seizure frequency and antiepileptic drug (AED) polytherapy, although the estimates were imprecise and the associations not statistically significant. Insufficient data on seizure frequency and changes in AED dosage due to incomplete case records were associated with high RRs. We found no association between risk of suicide and any particular AED, with type of epilepsy, or localization or lateralization of epileptogenic focus on EEG [RR = 0.3 (95% CI, 0.1-1.7)]. CONCLUSIONS: The profile of the epilepsy patient who commits suicide that emerges from our study is a patient with early onset (particularly onset during adolescence) but not necessarily severe epilepsy, psychiatric illness, and perhaps inadequate neurologic follow-up. Previous reports of an association with temporal lobe epilepsy could not be confirmed.     

Aberrant sprouting and downregulation of tyrosine hydroxylase in lesioned nigrostriatal dopamine neurons induced by long-lasting overexpression of glial cell line derived neurotrophic factor in the striatum by lentiviral gene transfer

The effects of sustained (up to 9 months) striatal overexpression of glial cell line derived neurotrophic factor (GDNF) on lesioned nigrostriatal dopamine (DA) neurons was studied using a recombinant lentiviral (rLV) vector to deliver GDNF into the striatum 4 weeks prior to the creation of an intrastriatal 6-hydroxydopamine lesion. The results of the amphetamine-induced rotation suggested an initial partial protection followed by a complete recovery, whereas the spontaneous motor behaviors remained impaired. There was a clear protection of the nigral tyrosine hydroxylase (TH)-positive neurons in the rLV-GDNF group compared to rats injected with the control vector encoding green fluorescent protein (GFP) (70 and 20% of the intact side, respectively). However, the striatal TH+ fiber density was equally reduced (to 20% of the intact side) in both groups. Further morphological analyses indicated that the nigrostriatal projections of the DA neurons were indeed preserved in the GDNF group. The axonal projections were visualized using two independent methods: First, retrograde labeling of the nigral cell bodies by intrastriatal Fluoro-Gold injections showed that the majority of rescued cells in the GDNF group had preserved axonal projections to striatum. Second, injections of a recombinant adeno-associated viral vector expressing GFP into the nigra was used to anterogradely fill the DA neurons and their projections with GFP protein. GFP immunostaining clearly demonstrated that the fibers of the nigral DA cells were preserved along the nigrostriatal pathway and innervated large parts of the striatum, but did not express TH at detectable levels. In addition, fiber sprouting was observed in the globus pallidus, entopeduncular nucleus, and substantia nigra, corresponding to areas where GDNF protein was released. The lack of functional recovery in the spontaneous motor behaviors may, at least in part, be explained by this extensive aberrant fiber sprouting in the downstream striatal target nuclei and/or decreased synthesis of dopamine in the striatum.     

Altered tubulin and neurofilament expression and impaired axonal growth in diabetic nerve regeneration

Cytoskeletal protein expression in sensory neurons and sciatic nerve axonal growth were examined in type 1 diabetic BB/Wor rats after sciatic nerve crush injury. Diabetic male rats were subjected to sciatic nerve crush at 6 wk of diabetes. L4 and L5 dorsal root ganglia (DRG) mRNA expression of low and medium molecular weight neurofilaments (NF-L, NF-M), betaII- and betaIII-tubulin as well as protein expression of NF-L, NF-M, and beta-tubulin were examined at various time points following crush injury and compared with age- and sex-matched non-diabetic BB/Wor rats. Steady state mRNA expression of NF-L, NF-M, betaII- and betaIII-tubulin were decreased in diabetic DRG. NF-L and NF-M proteins were also decreased in DRG of uncrushed diabetic animals. After crush injury, betaII- and betaIII-tubulin mRNA were upregulated in control animals at day 2 and day 6, respectively, and beta-tubulin protein showed similarly increased expression after crush injury, while such upregulations did not occur in diabetic animals. Conversely, mRNA and protein expressions of NF-L, NF-M were downregulated to a lesser extent in diabetic animals compared to control rats. These changes were associated with impaired axonal elongation and caliber growth of regenerating fibers in diabetic rats. We propose that upregulation of tubulin has a negative feedback on NF expression in response to nerve injury, as seen in control rats. The absence of this upregulation in diabetic animals may impair its regulatory effect on NF expression and contribute to perturbed nerve regeneration seen in diabetic nerve.     

Management of levodopa-induced dyskinesia

There are three main therapeutic strategies to manage levodopa-induced dyskinesias in parkinsonian patients     

Influence on coagulation activity by subcutaneous LMW heparin as an adjuvant treatment to fibrinolysis in acute myocardial infarction

In this study, which includes 101 patients with acute ST segment-elevated myocardial infarction, we investigated the influence on the increased coagulation activity after streptokinase treatment by adding low-molecular-weight (LMW) heparin or placebo and the relation between the coagulation activity and ischemic episodes, coronary patency, and mortality. The expected increase of prothrombin fragment 1+2 (F1+2), thrombin-antithrombin (TAT), and D-dimer were significantly attenuated at 2, 6, and 18 h (D-dimer only at 18 h) in the dalteparin group compared to placebo. Ischemic episodes during the first 24 h appeared significantly more often in patients with F1+2 levels above the median at 18 h. There was a tendency to a lower frequency of Thrombolysis In Myocardial Infarction Trial (TIMI) grade 3 flow in the infarct-related artery in patients with TAT and D-dimer levels above the median at 18 h. F1+2, TAT, and D-dimer were significantly higher after 18, 6, and 18 h, respectively, in the deceased compared to surviving patients. Also, the lack of reduction of the levels of F1+2 between 6 and 18 h was related to a raised mortality. In conclusion, adjuvant treatment with LMW heparin to streptokinase attenuates increased coagulation activity. This might be of importance as remaining high coagulation activity is associated with signs of early reocclusion and raised mortality.     

C-peptide prevents hippocampal apoptosis in type 1 diabetes

To explore mechanisms underlying central nervous system (CNS) complications in diabetes, we examined hippocampal neuronal apoptosis and loss, and the effect of C-peptide replacement in type 1 diabetic BB/W rats. Apoptosis was demonstrated after 8 months of diabetes, by DNA fragmentation, increased number of apoptotic cells, and an elevated ratio of Bax/Bcl-xL, accompanied by reduced neuronal density in the hippocampus. No apoptotic activity was detected and neuronal density was unchanged in 2-month diabetic hippocampus, whereas insulin-like growth factor (IGF) activities were impaired. In type 1 diabetic BB/W rats replaced with C-peptide, no TdT-mediated dUTP nick-end labeling (TUNEL)-positive cells were shown and DNA laddering was not evident in hippocampus at either 2 or 8 months. C-peptide administration prevented the preceding perturbation of IGF expression and reduced the elevated ratio of Bax/Bcl-xL. Our data suggest that type 1 diabetes causes a duration-dependent programmed cell death of the hippocampus, which is partially prevented by C-peptide.     

Serum nerve growth factor concentration and its role in the preclinical stage of dementia

OBJECTIVE: Nerve growth factor is important for the development and function of the cholinergic basal forebrain. The authors examined the hypothesis that the concentration of nerve growth factor is lower than normal in the preclinical phase of neurodegenerative dementia, especially Alzheimer's disease. METHOD: The serum nerve growth factor concentration of subjects from the Berlin Aging Study and the Berlin Memory Clinic who later developed Alzheimer's disease were compared with those of subjects who were free of dementia and subjects who were already suffering from Alzheimer's disease. RESULTS: There were 17 subjects in each group, matched for age and sex. The three groups differed in log-10-transformed mean nerve growth factor concentrations: 1.62 (SD=0.59) for the healthy comparison subjects, 0.92 (SD=0.30) for the subjects with preclinical dementia, and 1.44 (SD=0.61) for the subjects with Alzheimer's disease. CONCLUSIONS: These results support the hypothesis of disturbed nerve growth factor regulation in the serum of patients with preclinical Alzheimer's disease. Mechanisms by which these disturbances appear are unclear, but they may reflect the situation in the preclinical Alzheimer's disease brain.     

CFTMEA 2000 : nouvelle version de la Classification française des troubles mentaux de l’enfant et de l’adolescent

The CFTMEA 2000 is the fourth version of the french classification. The authors did not change the principles or the uses of the previous version, but introduced various changes in axis I, as well as equivalencies with the ICD-10; an axis I appears for babies (0-3 years). The axis II categories remain inchanged for somatic factors as well as environmental ones.     

Validation of a questionnaire for measurement of beliefs about the climacteric

OBJECTIVE: To design an instrument for measuring beliefs about the social, psychological, and physiological consequences of women's climacteric stage. MATERIAL AND METHODS: The study included 340 women affiliated to Instituto de Seguridad y Servicios Sociales para los Trabajadores del Estado (Institute for Social Services and Security for State Workers, ISSSTE) (age mean = 49.46, (SD 7.92). The mean number of pregnancies in the sample was 3.75 (SD 2.57), and the mean number of born children was 3.21 (SD 2.19); 48% of women were premenopausal, 10.9% perimenopausal, and 40.6% postmenopausal. The instrument consisted of 25 items. RESULTS: A factorial analysis with Varimax rotation was carried out. Four factors were confirmed: disadvantages (alpha = 0.769), advantages (alpha = 0.839), physiological (alpha = 0.659), and psychological (alpha = 0.711). CONCLUSION: This instrument shows good internal consistency, and measures four climacteric belief groups: a) beliefs on disadvantages, b) beliefs on advantages, c) beliefs on physiological ailments, and d) beliefs on psychological symptoms. All three confirmed dimensions of the climacteric phase have been proposed in other studies.     

Peripheral multineuritis pointing at systemic sarcoidosis

We report a patient with a peripheral neuropathy as the first symptom of sarcoidosis. The systemic illness was proved by the presence of typic granulomes in the bone marrow. The fact that sarcoidosis is the cause for the neuropathy is supported by the temporary relation and by the good response of all clinical picture to the corticosteroid therapy.Sarcoid neuropathy can rarely be the presenting feature of sarcoidosis.