Giacomo Della Marca

Predictors of poor neurological outcome in adult comatose survivors of cardiac arrest: A systematic review and meta-analysis. Part 2: Patients treated with therapeutic hypothermia

AIMS AND METHODS To systematically review the accuracy of early (≤7 days) predictors of poor outcome, defined as death or vegetative state (Cerebral Performance Categories [CPC] 4-5) or death, vegetative state or severe disability (CPC 3-5), in comatose adult survivors from cardiac arrest (CA) treated using therapeutic hypothermia (TH). Electronic databases were searched for eligible studies. Sensitivity, specificity, and false positive rates (FPR) for each predictor were calculated. Quality of evidence (QOE) was evaluated according to the GRADE guidelines. RESULTS 37 studies (2403 patients) were included. A bilaterally absent N20 SSEP wave during TH (4 studies; QOE: Moderate) or after rewarming (5 studies; QOE: Low), a nonreactive EEG background (3 studies; QOE: Low) after rewarming, a combination of absent pupillary light and corneal reflexes plus a motor response no better than extension (M≤2) (1 study; QOE: Very low) after rewarming predicted CPC 3-5 with 0% FPR and narrow (<10%) 95% confidence intervals. No consistent threshold for 0% FPR could be identified for blood levels of biomarkers. In 6/8 studies on SSEP, in 1/3 studies on EEG reactivity and in the single study on clinical examination the investigated predictor was used for decisions to withdraw treatment, causing the risk of a self-fulfilling prophecy. CONCLUSIONS in the first 7 days after CA, a bilaterally absent N20 SSEP wave anytime, a nonreactive EEG after rewarming or a combination of absent ocular reflexes and M≤2 after rewarming predicted CPC 3-5 with 0% FPR and narrow 95% CIs, but with a high risk of bias.

Management of status dystonicus: Our experience and review of the literature

Status dystonicus (SD) is a life threatening disorder that develops in patients with both primary and secondary dystonia, characterized by acute worsening of symptoms with generalized and severe muscle contractions. To date, no information is available on the best way to treat this disorder. We review the previously described cases of SD and two new cases are reported, one of which occurring in a child with static encephalopathy, and the other one in a patient with pantothenate kinase‐associated neurodegeneration. Both patients were admitted to an intensive care unit and treated with midazolam and propofol. This approach proved to be useful in the former while the progressive nature of the dystonia of the second patient required the combination of intrathecal baclofen infusion and bilateral pallidal deep brain stimulation. We believe that a rapid and aggressive approach is justified to avoid the great morbidity and mortality which characterize SD. Our experience, combined with the data available in the literature, might permit to establish the best strategies in managing this rare and severe condition.

Sleep cyclic alternating pattern in normal school-age children

OBJECTIVES To evaluate cyclic alternating pattern (CAP) in sleep of school-age children in order to obtain a standardized database for CAP parameters in this age range. METHODS CAP parameters were quantified in 10 normal healthy subjects (6 males and 4 females, mean age 8.3 years; range 6-10 years). All subjects underwent polysomnography recordings for two consecutive nights in a standard laboratory setting. Sleep data were stored on computer using a 16-channel polysomnography digital system. Sleep macrostructure was visually scored according to the criteria by Rechtschaffen and Kales (Brain Information Service/Brain Research Institute, University of California, Los Angeles, 1968); CAP was visually scored following the criteria by Terzano et al. (Sleep Med 2 (2001) 537). RESULTS CAP rate showed a progressive increase with the deepness of sleep, with high values during slow wave sleep (SWS). CAP time showed its longest duration during non-REM (NREM) sleep stage 2 (S2), followed by SWS and sleep stage 1 (S1). No differences across NREM sleep stages were found for CAP cycle and phase B mean duration; on the contrary, phase A showed longer duration during SWS than in S1 and S2. Phases A1 were the most numerous (84.45%) followed by A3 (9.14%) and by A2 (6.44%). The distribution of phases A subtypes across NREM stages showed significant differences for the A1 subtypes that occurred more frequently during SWS than in S2 and S1 (and during S2 than in S1). Subtypes A3 were more frequent during S1 than SWS while no differences were found for subtype A2. The analysis of A1 interval distribution showed a log-normal-like distribution with a peak around 25 s for the A1 phases and no clear peak for A2-A3 phases. CONCLUSIONS The analysis of CAP in school-age children is characterized by an increase of CAP rate during SWS and a high percentage of A1 phases. The distribution of interval between consecutive A1 phases showed a peak around 25 s.

Paraneoplastic diseases associated with thymoma.

BackgroundThymoma is frequently associated with paraneoplastic diseases (PDs), most commonly with myasthenia gravis (MG). This association is thought to depend on thymoma’s capacity to produce and export T lymphocytes.Objective(1) To determine the frequency and characteristics of thymoma-associated PDs other than MG; (2) to evaluate T cell maturation in thymomas with and without PDs.MethodsWe studied 260 patients with thymoma (associated with MG in 228). The occurrence of PDs was monitored together with the tumor outcome. Phenotypic characterization of thymocyte subsets in 14 thymoma samples (7 with and 7 without MG) was performed by FACS.ResultsA total of 47 PDs was diagnosed in 41/260 patients (15.8 %). Neurological PDs included neuromyotonia, limbic encephalitis, polymyositis, subacute hearing loss, psychosis and sleep disorders. A broad spectrum of nonneurological PDs were observed, among these, hematological and cutaneous diseases prevailed. Like MG, these disorders occurred either in the presence of the thymoma or at different times after thymomectomy; their onset often heralded a tumor recurrence. In thymomas from MG subjects, we found an increased proportion of fully mature CD4 single positive (SP) thymocytes and a reduced frequency of CD4SPCD25+ cells; the latter finding may reflect a deficient generation of T regulatory cells, a reduced intratumorous activation of T cells, or both.ConclusionsWe confirm the strong association of thymoma with PDs. These disorders often occurred in MG patients and their course in relation to thymoma was similar to that of MG. In accordance with previous observations, we found some alterations in the intratumorous production of mature CD4+ T cells that could be involved in the pathogenesis of paraneoplastic autoimmunity.

Rivastigmine as alternative treatment for refractory REM behavior disorder in Parkinson's disease

We report on a double‐blind, crossover pilot trial for the treatment of rapid eye movement behavior disorder (RBD) in 12 patients with Parkinsons disease in whom conventional therapy failed.

Oxcarbazepine improves mood in patients with epilepsy.

This study prospectively examined whether continued add-on treatment with oxcarbazepine (OXC) is associated with quantitative improvement in mood and anxiety symptoms in adult patients with partial epilepsy. Depressive symptoms and anxiety were assessed by clinical interview using the Hamilton Depression Rating Scale (HDRS), the Cornell Dysthymia Rating Scale (CDRS), the Beck Depression Inventory (BDI), and the Hamilton Anxiety Rating Scale (HARS). Forty controls (patients with epilepsy treated with antiepileptic drugs other than OXC) and 40 OXC-treated patients were enrolled and completed the study. In our study, a significant improvement in affect, as measured by the CDRS, was demonstrated during the course of OXC treatment for 3 months. HDRS and BDI scores also declined in the OXC-treated group, but these decreases did not reach statistical significance. In addition, 28 of 40 OXC-treated subjects who were dysthymic by CDRS criteria on study entry (score > or =20) demonstrated affective improvement consistent with a treatment-related antidepressant effect (score <20). Although our results do not provide conclusive evidence supporting the specific use of OXC as an antidepressant, the significant decline in dysthymic symptoms in OXC-treated subjects compared with controls lends support to the hypothesis that OXC improves mood.

Bipolar Disorder and Epilepsy: A Bidirectional Relation? Neurobiological Underpinnings, Current Hypotheses, and Future Research Directions

A number of studies have demonstrated that affective disorders in epilepsy represent a common psychiatric comorbidity; however, most of the classic neuropsychiatric literature focuses on depression, which is actually prominent, but little is known about bipolar depression, and very little about mania, in epilepsy. Biochemical, structural, and functional abnormalities in primary bipolar disorder could also occur secondary to seizure disorders. The kindling paradigm, invoked as a model for understanding seizure disorders, has also been applied to the episodic nature of bipolar disorder. In bipolar patients, changes in second-messenger systems, such as G-proteins, phosphatidylinositol, protein kinase C, myristoylated alanine-rich C kinase substrate, or calcium activity have been described, along with changes in c-fos expression. Common mechanisms at the level of ion channels might include the antikindling and the calcium-antagonistic and potassium outward current-modulating properties of antiepileptic drugs. All these lines of research appear to be converging on a richer understanding of neurobiological underpinnings between bipolar disorder and epilepsy. Mania, which is the other side of the coin in affective disorders, may represent a privileged window into the neurobiology of mood regulation and the neurobiology of epilepsy itself. Future research on intracellular mechanisms might become decisive for a better understanding of the similarities between these two disorders. NEUROSCIENTIST 13(4):392—404, 2007. DOI: 10.1177/1073858407301117

Microstructure of sleep in depressed patients according to the cyclic alternating pattern

BACKGROUND The aim of this study was to evaluate the microstructure of the EEG sleep of depressed subjects by cyclic alternating pattern (CAP) analysis. METHODS 78 patients affected by major depression and 18 control subjects matched for age and sex underwent a full night polysomnographic study. RESULTS A significant increase in CAP rate (60 versus 35%) was found in the patients group compared to controls while no significant difference was found with the traditional analysis. CONCLUSION In depressed subjects CAP analysis is able to show a microstructural sleep impairment, which is not evident at the macrostructural level, providing an objective measure of sleep disturbance in those patients.

Heart rate and heart rate variability modification in chronic insomnia patients.

Chronic insomnia is highly prevalent in the general population, provoking personal distress and increased risk for psychiatric and medical disorders. Autonomic hyper-arousal could be a pathogenic mechanism of chronic primary insomnia. The aim of this study was to investigate autonomic activity in patients with chronic primary insomnia by means of heart rate variability (HRV) analysis. Eighty-five consecutive patients affected by chronic primary insomnia were enrolled (38 men and 47 women; mean age: 53.2 ± 13.6). Patients were compared with a control group composed of 55 healthy participants matched for age and gender (23 men and 32 women; mean age: 54.2 ± 13.9). Patients underwent an insomnia study protocol that included subjective sleep evaluation, psychometric measures, and home-based polysomnography with evaluation of HRV in wake before sleep, in all sleep stages, and in wake after final awakening. Patients showed modifications of heart rate and HRV parameters, consistent with increased sympathetic activity, while awake before sleep and during Stage-2 non-REM sleep. No significant differences between insomniacs and controls could be detected during slow-wave sleep, REM sleep, and post-sleep wake. These results are consistent with the hypothesis that autonomic hyper-arousal is a major pathogenic mechanism in primary insomnia, and confirm that this condition is associated with an increased cardiovascular risk.

Sleep disordered breathing in children and adolescents with Chiari malformation type I.

STUDY OBJECTIVES Chiari malformation Type I (CM-I) has been associated with sleep disordered breathing (SDB). The aim of this study was to evaluate the prevalence of SDB in CM-I and its clinical correlates in a population of children and adolescents. METHODS Fifty-three consecutive children and adolescents affected by CM-I were enrolled (27 girls and 26 boys, mean age 10.3 ± 4.3, range: 3-18 years). All patients underwent neurological examination, MRI, and polysomnography (PSG). Otorhinolaryngologic clinical evaluation was performed in patients with polysomnographic evidence of sleep-related upper airway obstruction. RESULTS Mean size of the herniation was 9.5 ± 5.4 mm. Fourteen patients had syringomyelia, 5 had hydrocephalus, 31 presented neurological signs, 14 had epileptic seizures, and 7 reported poor sleep. PSG revealed SDB in 13 subjects. Patients with SDB, compared to those without SDB, had a higher prevalence hydrocephalus (p = 0.002), syringomyelia (p = 0.001), and neurological symptoms (p = 0.028). No significant difference was observed in age, gender, prevalence of epilepsy, and size of the herniation. Obstructive SDB was associated with syringomyelia (p = 0.004), whereas central SDB was associated with hydrocephalus (p = 0.034). CONCLUSIONS In our population of CM-I patients the prevalence of SDB was 24%, lower than that reported in literature. Moreover, our findings suggest that abnormalities in cerebrospinal fluid dynamics in CM-I, particularly syringomyelia and hydro-cephalus, are associated with SDB.