Treatment of Status Epilepticus in Adults: Guidelines of the Italian League Against Epilepsy

Summary:  Status epilepticus (SE) is a medical emergency which can lead to significant morbidity and mortality and requires prompt diagnosis and treatment. SE is differentiated into generalized or partial SE on the basis of its electro-clinical manifestations. The guidelines for the management of SE produced by the Italian League against Epilepsy also distinguish three different stages of SE (initial, established and refractory), based on time elapsed since the onset of the condition and responsiveness to previously administered drugs. Treatment should be started as soon as possible, particularly in generalized convulsive SE, and should include general support measures, drugs to suppress epileptic activity and, whenever possible, treatments aimed at relieving the underlying (causative) condition. Benzodiazepines are the first line antiepileptic agents, and i.v. lorazepam is generally preferred because it is associated with a lower risk of early relapses. If benzodiazepines fail to control seizures, i.v. phenytoin is usually indicated, though i.v. phenobarbital or i.v. valproate may also be considered. Refractory SE requires admission to an intensive care unit (ICU) to allow adequate monitoring and support of respiratory, metabolic and hemodynamic functions and cerebral electrical activity. In refractory SE, general anesthesia may be required. Propofol and thiopental represent first line agents in this setting, after careful assessment of potential risks and benefits.     

The Parkinson-Control study: a 1-year randomized, double-blind trial comparing piribedil (150 mg/day) with bromocriptine (25 mg/day) in early combination with levodopa in Parkinson's disease.

Dopamine agonists have been recommended as early treatment for Parkinson's disease (PD), alone or combined with levodopa. Piribedil is a non-ergot selective D(2)/D(3) agonist with alpha(2) antagonist properties shown to be effective in the treatment of PD. This 12-month international, randomized, double-blind trial aimed to assess the efficacy of piribedil 150 mg versus bromocriptine 25 mg, in early combination with levodopa in Stage I to III PD patients. Motor efficacy was assessed using the Unified Parkinson's Disease Rating Scale (UPDRS III, Items 18-31) as improvement from baseline. Response rate was defined as a 30% improvement. Among the 425 randomly assigned patients, 178 were also included in a substudy on cognitive follow-up evaluated by a dysexecutive syndrome oriented battery. A relevant improvement in UPDRS III over the 12-month study duration was observed both in the piribedil and bromocriptine groups (-7.9 +/- 9.7 points from baseline versus -8.0 +/- 9.5; not significant [n.s.]) with a response rate of 58.4% and 55.3% (n.s.), respectively. Piribedil and bromocriptine resulted in similar improvement on all UPDRS III subscores. Piribedil patients required less levodopa dose increase than those on bromocriptine. Cognitive performance remained generally unchanged in both groups, with a significant effect of piribedil limited to the Wisconsin Card Sorting Test. An overall good tolerability of piribedil was observed. Early combination of piribedil 150 mg with levodopa resulted in significant long-term improvement of all motor symptoms in PD patients insufficiently controlled by levodopa alone. Taking into account both efficacy and acceptability in the long-term, piribedil proved in this bromocriptine controlled study to be an effective and safe treatment for PD.     

Correlation of age-associated increases in follicle stimulating hormone secretion with decreases in antral follicles: failure of progesterone-induced acyclicity to prevent these changes.

It is well known that the number of follicles in the mammalian ovary decreases with age. In light of previous data from this laboratory showing age-related alterations in the secretion and production of follicle-stimulating hormone (FSH) in rats by 5-6 months of age, one objective of the present study was to determine if alterations in FSH secretion were accompanied by changes in the number of antral follicles. A second objective of this study was to determine whether or not interruption of cyclic activity by continuous progesterone (P) treatment could decelerate age-associated changes in FSH secretion possibly by retarding the depletion of follicles through ovulation. For this study, one group of 4-day cycling, 7-week-old rats received one empty Silastic implant while another group received 3-40 mm implants containing 30 mm crystalline P. Implants were replaced every 2 weeks until the animals were 5 months old. Progesterone-implanted rats were acyclic during treatment exhibiting predominantly leukocytic vaginal smears. Regular 4-day cycles resumed when P implants were withdrawn (rats approximately 5-6-months-old). A group of 2-3-month-old untreated rats were used for comparison. As expected from our previous results, serum FSH levels at 1600 h on estrus were significantly higher in 5-6-month-old rats receiving empty capsules than in younger rats. Serum FSH concentrations measured in P-treated rats at this time also were significantly higher than levels of this gonadotropin measured in younger rats. Ovaries of older control and P-treated rats contained significantly fewer medium and large antral follicles (greater than 250 microns) than the ovaries of younger rats despite the curtailment of estrous cyclicity and ovulation by continuous P treatment. Interestingly, P treatment prevented the age-associated decrease in thymus weight. Taken together, the present observations suggest that a decrease in the number of growing follicles may be a factor contributing to early age-related alterations in FSH secretion. Furthermore, the prevention (at least temporarily) of age-related thymic involution by P treatment may be indicative of an interrelationship between thymic and reproductive aging.     

Frontal white matter volume and delta EEG sources negatively correlate in awake subjects with mild cognitive impairment and Alzheimer's disease.

OBJECTIVE: A relationship between brain atrophy and delta rhythmicity (1.5-4 Hz) has been previously explored in Alzheimer's disease (AD) subjects [Fernandez A, Arrazola J, Maestu F, Amo C, Gil-Gregorio P, Wienbruch C, Ortiz T. Correlations of hippocampal atrophy and focal low-frequency magnetic activity in Alzheimer disease: volumetric MR imaging-magnetoencephalographic study. Am J Neuroradiol. 2003 24(3):481-487]. In this study, we tested the hypothesis that such a relationship does exist not only in AD patients but also across the continuum of subjects with mild cognitive impairment (MCI) and AD. METHODS: Resting, eyes-closed EEG data were recorded in 34 MCI and 65 AD subjects. EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), and beta 2 (20-30 Hz). EEG cortical sources were estimated by LORETA. Cortical EEG sources were correlated with MR-based measurements of lobar brain volume (white and gray matter). RESULTS: A negative correlation was observed between the frontal white matter and the amplitude of frontal delta sources (2-4 Hz) across MCI and AD subjects. CONCLUSIONS: These results confirmed for the first time the hypothesis that the sources of resting delta rhythms (2-4 Hz) are correlated with lobar brain volume across MCI and AD subjects. SIGNIFICANCE: The present findings support, at least at group level, the 'transition hypothesis' of brain structural and functional continuity between MCI and AD.     

Giant cavernous hemangiomas: Diagnosis and surgical strategies

From January, 1972 to June, 1989, 51 patients with liver hemangiomas (32 females and 19 males, mean age 35 years) were evaluated for surgical treatment. Diameters of the masses were 5 cm to 20 cm (median 8.5 cm). Nine of the patients had already been treated for cancer. Twenty-two (43.1%) of the 51 patients were symptomatic and 29 (56.9%) patients were asymptomatic. In 34 patients (66.7%) a definite diagnosis of hemangioma was made by scintiscan and/or ultrasound and/or computed tomography and/or angiography while in the remaining 17 (33.3%) patients the diagnosis was uncertain. The most common indications for resection were the presence of a symptomatic angioma, a symptomatic mass with an uncertain diagnosis, and/or lack of a definite pre-operative diagnosis. Surgery was performed on 25 patients. Ten anatomic and 15 atypical resections or enucleations were performed. There were no postoperative deaths. Two further patients, operated for probable hemangioma, were found to have primary hepatic malignancies. In the 26 unresected patients, no complications were observed during follow-up. In 3 patients, hemangioma enlargement was detected by ultrasound, but there were no symptoms. As cavernous liver hemangiomas are now more reliably diagnosed and their natural history is usually uneventful, surgery can be avoided in most cases. However, when a non-resection policy is adopted, an exact diagnosis is essential in order to rule out primary or metastatic cancer. Surgical exploration and treatment should be limited to symptomatic or complicated cases as well as to patients with an uncertain diagnosis.

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Resumen Cincuenta y un pacientes con hemangiomas del higado (32 mujeres y 19 hombres, edad promedio 35 años) fueron valorados en cuanto a tratamiento quirúrgico en el período enero 1972 a junio de 1989; el diámetro de las lesiones oscilo entre 5 y 20 cm (promedio 8.5 cm). Nueve de los pacientes ya habían sido tratados por cáncer; 22/51 (43.1%) estaban sintomáticos y 29/51 (56.9%) eran asintomáticos. En 34/51 (66.7%) se hizo el diagnóstico definitivo de hemangioma mediante escintigrafia y/o ultrasonido y/o tomografía computadorizada y/o angiografia, en tanto que en los otros 17 pacientes (33.3%) el diagnóstico resultó incierto. Las indicaciones más comunes para resección fueron: presencia de un angioma sintomático, una masa asintomática con diagnóstico incierto y/o ausencia de diagnóstico preoperatorio definitivo. Se practicó cirugía en 25/51 pacientes, habiéndose realizado 10 resecciones anatómicas y 15 resecciones atípicas o enucleaciones. No hubo muertes postoperatorias. Otros dos pacientes operados por probable hemangioma demostraron tener neoplasias malignas hepáticas primarias. En los 26 pacientes no resecados no se observaron complicaciones durante el seguimiento; en tres casos se detectó ensanche del hemangioma en el examen con ultrasonido, pero no se presentaron síntomas. Puesto que actualmente los hemangiomas cavernosos del hígado pueden ser diagnosticados con mayor certeza y puesto que su historia natural generalmente está libre de complicaciones es posible evitar la cirugía en la mayoría de los casos. Sin embargo, cuando se pretenda adoptar una política de no resección es esencial establecer el diagnóstico exacto para excluir la posibilidad de un cáncer primario o metastásico. La exploración y el tratamiento quirúrgicos debe permanecer limitados a los hemangiomas sintomáticos o complicados, y en ningún caso deben significar riesgo para el paciente.

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Résumé De Janvier 1972 à Juin 1989, 51 patients ayant un hémangiome du foie (32 femmes et 19 hommes, âge moyen 35 ans) ont été examinés en vue d'une exérèse chirurgicale. Le diamètre de la lésion variait entre 5 et 20 cm (médiane = 8.5 cm). Neuf des patients avaient déjà été traités pour un cancer; 22/51 (43.1%) étaient symptomatiques alors que 29/51 (56.9%) étaient asymptomatiques. Chez 34/51 patients (66.7%), le diagnostic définitif d'hémangiome a été confirmé par scintigraphie et/ou échographie et/ou tomodensitométrie, alors que chez les 17 autres (33.3%), le diagnostic était uncertain. Les indications d'une résection les plus fréquentes étaient: la présence d'un angiome symptomatique, une masse symptomatique avec un diagnostic uncertain, et/ou absence de diagnostic définitif préopératoire. Vingt-cinq des 51 patients ont été opérés. Il y a eu 10 résections anatomiques et 15 résections atypiques ou énucléations. Il n'y a pas eu de mortalité postopératoire. Deux autres patients, traités pour ce que l'on soupçonnait être une probalbe hémangiome du foie, avaient en fait un cancer hépatique. Chez les 26 patients non résequés, il n'y avait pas eu de complication. Chez trois patients, on a mis en évidence une augmentation de volume par l'échographie, mais ces modifications ne s'accompagnait d'aucune symptomatologie. Comme on peut faire le diagnostic d'hémangiome carverneux du foie avec plus de fiabilité qu'avant, et comme on sait que leur histoire naturelle est généralement bénigne, on peut le plus souvent surseoir à l'exérèse chirurgicale. Cependant, il importe de toujours faire le diagnositc avec certitude, de façon à éliminer un cancer primitif ou sécondaire du foie.

     

Systemic fungemia and hepatic localizations of Fusarium solani in a liver transplanted patient: an emerging fungal agent.

The incidence of invasive fungal infection is increasing especially in the field of transplantation, affecting as many as 50% of bone marrow transplant (BMT) patients with neutropenia and 5-20% of solid-organ transplant (SOT) recipients. Fusarium species are soil saprophytes and plant pathogens. They may cause superficial mycoses or important opportunistic infections in patients with bone marrow suppression and neutropenia, they have been rarely described in solid organ recipients, and up to now there have been no reports of such infection in isolated liver transplanted patients. We describe a case of disseminated Fusarium solani infection with hepatic localization in a liver transplanted patient that resolved with the administration of amphotericin B. Our observation confirms that Fusarium spp. are emerging pathogens that may most frequently affect not only BMT patients and patients with hematological malignancies, but also SOT patients. They may cause both localized and disseminated infection. In conclusion, Fusarium spp. etiology should be considered in the context of infectious diseases following liver transplantation.     

Free copper and resting temporal EEG rhythms correlate across healthy, mild cognitive impairment, and Alzheimer's disease subjects.

OBJECTIVE: The present study tested the hypothesis that the serum copper abnormalities were correlated with alterations of resting electroencephalographic (EEG) rhythms across the continuum of healthy elderly (Hold), mild cognitive impairment (MCI), and AD subjects. METHODS: Resting eyes-closed EEG rhythms delta (2-4Hz), theta (4-8Hz), alpha 1 (8-10.5Hz), alpha 2 (10.5-13Hz), beta 1 (13-20Hz), beta 2 (20-30Hz), and gamma (30-40Hz), estimated by LORETA, were recorded in 17 Hold, 19 MCI, 27 AD- (MMSE< or =20), and 27 AD+ (MMSE20) individuals and correlated with copper biological variables. RESULTS: Across the continuum of Hold, MCI and AD subjects, alpha sources in parietal, occipital, and temporal areas were decreased, while the magnitude of the delta and theta EEG sources in parietal, occipital, and temporal areas was increased. The fraction of serum copper unbound to ceruloplasmin positively correlated with temporal and frontal delta sources, regardless of the effects of age, gender, and education. CONCLUSIONS: These results sustain the hypothesis of a toxic component of serum copper that is correlated with functional loss of AD, as revealed by EEG indexes. SIGNIFICANCE: The present study represents the first demonstration that the fraction of serum copper unbound to ceruloplasmin is correlated with cortical delta rhythms across Hold, MCI, and AD subjects, thus unveiling possible relationships among the biological parameter, advanced neurodegenerative processes, and synchronization mechanisms regulating the relative amplitude of selective EEG rhythms.     

Treatment of Hemorrhoids in Day Surgery: Stapled Hemorrhoidopexy vs Milligan–Morgan Hemorrhoidectomy

Background Recently, it has been demonstrated that surgical treatment of hemorrhoids in a day-care basis is possible and safe. The aim of this study was to compare the Longo stapled hemorrhoidopexy (SH) and the Milligan–Morgan hemorrhoidectomy (MMH). Methods One hundred seventy one patients (95 cases in SH group and 76 cases in MMH group) entered the study: 83 cases were III degree hemorrhoids, 88 IV degree. A priori and a post hoc power analysis were performed. Results, prospectively collected, were compared using chi squared test and student t test. Visual analog scale was used for pain evaluation. Postoperative pain, duration of pain, wound secretion, bleeding, resumption of a normal lifestyle, and postoperative complication were evaluated. Results Surgical time was 28.41 ± 10.78 for MMH and 28.30 ± 13.28 min in SH (P = 0.94). Postoperative pain was not different between MMH and SH during the first two postoperative days (4.73 ± 2.91 vs 5.1 ± 3.048; P = 0.4), during the following 6 days, patients treated with SH had less pain (4.63 ± 2.04 in MMH vs 3.60 ± 2.35 in SH; P = 0.006). In the SH group, seven patients needed further hospital stay for complicated course. SH showed higher incidence of anal fissure compared with MMH (6.3% vs 0%; P = 0.025) but no differences in urinary retention, anal stricture, urgency, or anal hemorrhage. Conclusions This study confirms that SH is associated with less postoperative pain and shorter postoperative symptoms, compared with MMH. SH may be a viable addition to the therapy for hemorrhoids with some advantages in early postoperative pain and some disadvantages in postoperative complications and costs.