Paolo Benna

Neonatal Hypoxia and Epileptic Risk: A Clinical Prospective Study

Summary: A historical cohort study was undertaken to determine the risk of epilepsy in a population of 371 newborns with an acute neurological disorder related to fetal and/or neonatal hypoxia compared with a control population of 362 normal newborns. The results showed that the risk of epilepsy was 5.1 times higher in the group of subjects affected at birth by a hypoxia‐related acute neurological syndrome than in the control group. (Although the incidence of epilepsy is higher in the first year of life, epileptic seizures connected to perinatal hypoxia may occur in early childhood or later on.) Also, there were frequently persistent neuropsychiatric disorders in children with perinatal hypoxia (5.4%). There was no difference in the two groups regarding the incidence of febrile convulsions. The data show that perinatal hypoxia plays a role in the etiology of epilepsy, although at birth the hypoxia might result in only a modest and oftentimes completely reversible neurological syndrome.

Clinical features, EEG findings and diagnostic pitfalls in juvenile myoclonic epilepsy: a series of 63 patients

Juvenile myoclonic epilepsy (JME) is a common idiopathic generalized epileptic syndrome distinctively characterized by myoclonic jerks often associated to generalized tonic-clonic seizures (GTCS) and typical absence seizures. In spite of typical clinical and EEG profiles, JME is widely underdiagnosed. In the present study we retrospectively revised clinical and EEG data of JME patients referring to our Epilepsy Service. A diagnosis of JME could be made in 63 patients, that is 5.7% of all the epileptic patients referring to our Service and 25.9% of those suffering from an idiopathic generalized epilepsy. General features as well as modality of onset and course of the syndrome of our JME subjects were in accordance with literature. Regarding EEG findings, asymmetries were detected in 38.1% of cases. At referral to our Service only 31.7% of JME patients were correctly diagnosed. Main factors responsible for misdiagnosis were failure in eliciting a history of myoclonic jerks and misinterpretation of myoclonic jerks as simple partial seizures. EEG asymmetries were misleading in 13 patients. In conclusion, a correct JME diagnosis is strictly dependent on the knowledge of the syndrome leading the interviewer to look for and correctly interpret myoclonic jerks whereas EEG is just an ancillary diagnostic tool.

The long-term effect of vagus nerve stimulation on quality of life in patients with pharmacoresistant focal epilepsy: The PuLsE (Open Prospective Randomized Long-term Effectiveness) trial

To evaluate whether vagus nerve stimulation (VNS) as adjunct to best medical practice (VNS + BMP) is superior to BMP alone in improving long‐term health‐related quality of life (HRQoL).

Propofol analgesia in central pain: Preliminary clinical observations

Propofol, an intravenous general anaesthetic, has been reported to relieve some forms of pruritus at subhypnotic doses. We assessed its effectiveness in 32 patients with several kinds of non-malignant chronic pain, in a placebo-controlled, double-blind study. We found that central pain, but not neuropathic pain, is at least partially controlled by propofol at subhypnotic doses, without major side-effects. In particular, allodynia associated with central, but no neuropathic, pain has been completely controlled. Propofol analgesia leads to renormalization of brain metabolism as seen on single photon emission computed tomography. We conclude that propofol may help in the diagnosis of central pain, particularly in unclear cases, and also in treatment. Possible mechanisms of action are discussed.

Peripheral-type benzodiazepine receptors and diazepam binding inhibitor-like immunoreactivity distribution in human peripheral blood mononuclear cells

Peripheral-type benzodiazepine receptors (pBZr) in human lymphocytes have been detected only in mixtures of peripheral blood mononuclear cells (PBMC). The present investigation was designed to describe precisely the location of pBZr in the various sets and subsets of PBMC, purified using monoclonal antibodies to specific PBMC surface markers. Site densities and affinities of pBZr were measured in the intact cells by conventional binding, using 3H-PK 11195 as a ligand. Moreover, we used a specific radioimmunoassay to identify in these cells the presence of the polypeptide diazepam binding inhibitor (DBI), a putative endogenous ligand for various benzodiazepine receptors including the peripheral type. Two major findings are derived from these studies: first, the coexistence of pBZr and DBI, or closely related immunoreactive material, in all major lymphocyte sets and subsets, as well as in monocytes. And second, the significant correlation (r = 0.87, p < 0.001) observed between the density of pBZr in a given cell type and its abundance of DBI like-immunoreactivity (DBI-LI). For both pBZr and DBI-LI content the cell distribution was monocytes > B cells and large granular lymphocytes > T cells (CD3+ set or CD4+ and CD8+ subsets) (ANOVA: pBZr: F = 114.11, p < 0.001; DBI-LI: F = 20.79, p < 0.001). The results are discussed in terms of the possibility that DBI and pBZr might share a relevant interaction in immunocompetent elements, thereby contributing to a new route of connection between the immune and the nervous systems.

A functional polymorphism in the SCN1A gene does not influence antiepileptic drug responsiveness in Italian patients with focal epilepsy

A splice site variation (c.603‐91G>A or rs3812718) in the SCN1A gene has been claimed to influence efficacy and dose requirements of carbamazepine and phenytoin. We investigated the relationship between c.603‐91G>A polymorphism and response to antiepileptic drugs (AEDs) in 482 patients with drug‐resistant and 401 patients with drug‐responsive focal epilepsy. Most commonly used AEDs were carbamazepine and oxcarbazepine. The distribution of c.603‐91G>A genotypes was similar among drug‐resistant and drug‐responsive subjects, both in the entire population and in the groups treated with carbamazepine or oxcarbazepine. There was no association between the c.603‐91G>A genotype and dosages of carbamazepine or oxcarbazepine. These findings rule out a major role of the SCN1A polymorphism as a determinant of AED response.

Diazepam binding inhibitor-like immunoreactivity (DBI-LI) in human CSF: Correlations with neurological disorders

Cerebrospinal fluid (CSF) levels of the anxiogenic neuropeptide diazepam binding inhibitor (DBI) were determined by radioimmunoassay in 281 patients who underwent evaluation for neurological problems. Serial dilution curves and reverse-phase high pressure liquid chromatography showed that the immunoreactive material in CSF behaved just as authentic DBI extracted from human brain. Furthermore in the assay there was no evidence of interference from CSF samples deprived of DBI by immunoaffinity. In 82 patients with no evidence of major lesions in the central nervous system, who acted as controls, the CSF DBI content was shown to be age- and sex-related. No correlation was observed with the CSF protein concentration. In patients with different types of dementia, the levels of CSF DBI were significantly increased in a group with normal pressure hydrocephalus. No significant differences were found between Alzheimers disease, multi-infarct dementia, or dementia with Parkinsons disease and controls. In non-demented patients with Parkinsons disease the levels of DBI were increased in a subgroup with depressive disturbances whereas no differences was observed in the non-depressed cases. The content of DBI was markedly reduced in 5 cases with olivopontocerebellar atrophy and in 4 with spinocerebellar ataxia. In all the other disorders studied the levels of DBI were similar to or slightly lower (multiple sclerosis) than those of the controls. The origin of DBI in cerebrospinal fluid is uncertain; a number of various possibilities are discussed concerning the proposed role of DBI as modulator of brain GABAergic transmission.

Acquired etiological factors in 1,785 epileptic subjects: clinical-anamnestic research.

This study utilizes ciinicai and anamnestic data concerning epileptic subjects (males and females) of ages ranging between 1 month and 21 years.

Nonconvulsive status epilepticus due to a de novo contralateral focus during tiagabine adjunctive therapy

We describe a 30-year-old woman with an infantile-onset epilepsy due to a left temporal gliotic area who developed a nonconvulsive status epilepticus (NCSE) during tiagabine (TGB) adjunctive therapy. The ictal EEG recording showed a de novo right temporal focus not previously evident. After the i.v. administration of 4 mg lorazepam, the NCSE episode rapidly resolved and her usual left temporal EEG abnormalities reappeared. To our knowledge this is the first case of paradoxical seizure exacerbation associated with TGB therapy in which the clinical and EEG features are congruous with a new contralateral focus.

A novel homozygous change of CLCN2 (p.His590Pro) is associated with a subclinical form of leukoencephalopathy with ataxia (LKPAT)

ClC-2 is a plasma membrane chloride channel with widespread expression in the human body, including the brain. Its function is still being studied, although it is thought to have a role in ion and water homoeostasis in the brain. ClC-2 is part of a complex containing GlialCAM and MLC1. Both these genes are associated with autosomal recessive human leukodystrophies with intramyelinic oedema. Biallelic mutations in CLCN2 , encoding the ClC-2 channel, have been reported in patients with a rare form of leukoencephalopathy with ataxia (LKPAT; MIM #615651). No peculiar neurological features have been reported for this disease, although slight visual impairment due to chorioretinopathy or optic atrophy, mild ataxia, learning disabilities, and headaches are recurrent symptoms in patients. However, MRI shows a typical diagnostic pattern that consists of white matter signal abnormalities in the posterior limbs of the internal capsules, cerebral peduncles, pontine pyramidal tracts and in the middle cerebellar peduncles, associated with lower apparent diffusion coefficient values in most cases. Specific anomalies of brainstem auditory evoked potentials (BAEP) have also been described.1–3 Here, we report on a 52-year-old Moroccan woman presenting with mild and asymptomatic bilateral optic atrophy detected at a routine ophthalmological examination for presbyopia. Best-corrected high-contrast visual acuity was 20/20 in both eyes. Anterior segment and intraocular pressures were normal, and pupillary reflexes were present. On fundus biomicroscopy, mild pallor and excavation of the optic …