Neurophysiological assessment of the injured spinal cord: an intraoperative approach.

STUDY DESIGN: Prospective, observational study. OBJECTIVES: To assess the spinal cord function intraoperatively in subjects during spine stabilization for spinal cord trauma, by recording muscular (m-MEPs) and epidural motor evoked potentials (e-MEPs, D wave) along with cortical and epidural somatosensory evoked potentials (e-SEPs) and predicting the outcome of spinal cord injury (SCI). SETTING: Regional Trauma Center, Torino, Italy. METHODS: Fifty-five patients were intraoperatively studied during posterior spine stabilization surgery for traumatic SCI. In all, 21 of these had complete SCI, 14 an incomplete SCI-6 of them with central cord syndrome and 1 with central cord plus Brown Sequard syndrome-and 20 patients were neurologically uncompromised. RESULTS: The neurophysiologic profile of the complete SCI was the absence of both m-MEPs and e-MEPs caudally to the lesion site, associated with a lack of cortical and e-SEPs cranially to the lesion site. None of these patients recovered motor function in the follow-up. A clearly detectable caudal D wave was associated with motor recovery even in deeply paraparetic patients. In one neurologically incomplete patient a reversible deterioration of m-MEPs and e-MEPs was observed during the compression-distraction manoeuvre. CONCLUSION: Intraoperative neurophysiological evaluation of SCI patients can provide information about spinal cord function that is not retrievable by other clinical means and can correctly predict neurological outcome. Intraoperative testing during early stabilization of the spine of deeply paraparetic SCI patients provides additional information about their neurological profile.

Somatosensory- and motor-evoked potential monitoring during spine and spinal cord surgery.

STUDY DESIGN: Prospective, observational study. SETTING: Regional Trauma Center, Torino, Italy. OBJECTIVES: Complex spinal surgery carries a significant risk of neurological damage. The aim of this study is to determine the reliability and applicability of multimodality motor-evoked potentials (MEPs) and somatosensory-evoked potentials (SEPs) monitoring during spine and spinal cord surgery in our institute. METHODS: Recordings of MEPs to multipulse transcranial electrical stimulation (TES) and cortical SEPs were made on 52 patients during spine and spinal cord surgery under propofol/fentanyl anaesthesia, without neuromuscular blockade. RESULTS: Combined MEPs and SEPs monitoring was successful in 38/52 patients (73.1%), whereas only MEPs from at least one of the target muscles were obtained in 12 patients (23.1%); both MEPs and SEPs were absent in two (3.8%). Significant intraoperative-evoked potential changes occurred in one or both modalities in five (10%) patients. Transitory changes were noted in two patients, whereas three had persistent changes, associated with new deficits or a worsening of the pre-existing neurological disabilities. When no postoperative changes in MEP or MEP/SEP modalities occurred, it was predictive of the absence of new motor deficits in all cases. CONCLUSION: Intraoperative combined SEP and MEP monitoring is a safe, reliable and sensitive method to detect and reduce intraoperative injury to the spinal cord. Therefore, the authors suggest that a combination of SEP/MEP techniques could be used routinely during complex spine and/or spinal cord surgery.

A novel epilepsy mutation in the sodium channel SCN1A identifies a cytoplasmic domain for beta subunit interaction.

A mutation in the sodium channel SCN1A was identified in a small Italian family with dominantly inherited generalized epilepsy with febrile seizures plus (GEFS+). The mutation, D1866Y, alters an evolutionarily conserved aspartate residue in the C-terminal cytoplasmic domain of the sodium channel alpha subunit. The mutation decreased modulation of the alpha subunit by beta1, which normally causes a negative shift in the voltage dependence of inactivation in oocytes. There was less of a shift with the mutant channel, resulting in a 10 mV difference between the wild-type and mutant channels in the presence of beta1. This shift increased the magnitude of the window current, which resulted in more persistent current during a voltage ramp. Computational analysis suggests that neurons expressing the mutant channels will fire an action potential with a shorter onset delay in response to a threshold current injection, and that they will fire multiple action potentials with a shorter interspike interval at a higher input stimulus. These results suggest a causal relationship between a positive shift in the voltage dependence of sodium channel inactivation and spontaneous seizure activity. Direct interaction between the cytoplasmic C-terminal domain of the wild-type alpha subunit with the beta1 or beta3 subunit was first demonstrated by yeast two-hybrid analysis. The SCN1A peptide K1846-R1886 is sufficient for beta subunit interaction. Coimmunoprecipitation from transfected mammalian cells confirmed the interaction between the C-terminal domains of the alpha and beta1 subunits. The D1866Y mutation weakens this interaction, demonstrating a novel molecular mechanism leading to seizure susceptibility.

Generalized epilepsy with febrile seizures plus and severe myoclonic epilepsy in infancy: a case report of two Italian families.

"Generalized epilepsy with febrile seizures plus" (GEFS+) syndrome has been recently described. This term defines a heterogeneous group of generalized epilepsies observed in several members of large pedigree studies. The syndrome spectrum has been widened by including others forms of generalized epilepsy. We report two Italian families in which the fathers showed febrile seizure plus (FS+), and two sons had severe myoclonic epilepsy of infancy (SMEI). The clinical setting of each epileptic member of the family will be discussed, focusing on the relationship with the GEFS+ group, confirming its wide clinical spectrum. In fact, GEFS+ is different from most other epilepsy syndromes as it is defined not by a set of associated symptoms but by the genetic transmission of a predisposition to febrile convulsions and other seizures, with a variable expression in several members of the same pedigree, perhaps due to ionic channel dysfunction. SMEI could represent the most severe end of the spectrum.

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.

Peripheral-type benzodiazepine receptors on human blood mononuclear cells are not regulated by ovarian steroids.

Peripheral-type benzodiazepine receptors (pBZr) have been shown to be sensitive to hormonal perturbations, including changes in ovarian steroids. This study examines whether estradiol and progesterone modulate pBZr binding in membranes of human blood mononuclear cells, as measured by binding of both 3H-PK 11195 and 3H-Ro 5-4864. Our findings were negative. There was no steroidal modulation of pBZr binding to these membrane preparations in vivo in normal women studied at different sex-steroid phases of the menstrual cycle, or during 8-30 weeks of pregnancy. There was also no effect of hormones on the binding sites in cultures of mononuclear cells treated with estradiol or progesterone (up to 10(-5) M) over a period between 2 and 72 h. Further, we performed in vitro competition experiments, which showed that both steroids are not active at the pBZr. Our data suggest that pBZr located in human blood mononuclear cells are insensitive to the physiological variations of circulating female hormones.

An analysis of peripheral type benzodiazepine receptors on blood mononuclear cells during high dose steroid treatment of multiple sclerosis.

We report here a study of peripheral type benzodiazepine receptors (pBZr) in mononuclear cells (MNC) from blood of patients with multiple sclerosis (MS) during periods of stable and active disease and from normal controls. Most active MS patients were retested in a longitudinal study, both during a treatment with high dose steroids and while medication free. Active MS produces a significant decrease of receptor density compared with the controls whereas remission of the disease shows no effect. Four weeks of steroid treatment restore binding density to normal levels, and two weeks of drug withdrawal result in a small, but significant increase in number of the binding sites compared with the control value. We suggest that the number of pBZr in blood MNC might change during the clinical course and steroid therapy of MS.