Infective Causes of Epilepsy.

A wide range of infections of the central nervous system are responsible for both acute seizures and epilepsy. The pathogenesis and clinical semiology of the seizure disorders vary widely between the infective pathogens. The exact mechanisms underlying this are poorly understood, but appear, at least in part, to relate to the pathogen; the degree of cortical involvement; delays in treatment; and the host inflammatory response. The treatment of infective causes of seizures involves both symptomatic treatment with antiepileptic drugs and direct treatment of the underlying condition. In many cases, early treatment of the infection may affect the prognosis of the epilepsy syndrome. The greatest burden of acute and long-term infection-related seizures occurs in resource-poor settings, where both clinical and research facilities are often lacking to manage such patients adequately. Nevertheless, education programs may go a long way toward addressing the stigma, leading to improved diagnosis, management, and ultimately to better quality of life.

Thalamic versus midbrain tremor; two distinct types of Holmes' Tremor: a review of 17 cases.

INTRODUCTION: Holmes Tremor (HT) is a unique and debilitating movement disorder. It usually results from lesions of the midbrain and its connection but can also result from posterior thalamic injury. Clinical examination can help lesion localization between these two areas. We studied the clinical features and their radiological correlations to distinguish midbrain HT (HT-m) from thalamic HT (HT-t). METHODS: Retrospective review of 17 patients with a HT-type presentation was conducted. Tremor characteristics, associated clinical signs and radiological findings were studied. RESULTS: Eleven patients had a myorythmic rest tremor, large amplitude proximal tremor with goal-directed worsening, with or without mild distal dystonic posturing, representing HT-m. Six patients had slow, large amplitude proximal tremors and distal choreathetoid movements, significant proximal/distal dystonic posturing, associated with proprioceptive sensory loss, representing HT-t. Haemorrhagic lesions were the predominant cause of HT-m; whereas, ischaemia was more commonly associated with HT-t. CONCLUSION: When assessing patients with HT, attentiveness to the presence of associated signs in the affected limb, such as a proprioceptive sensory deficits and additional movement disorders, can aid lesion localisation, which can have implications for management.

Deep brain stimulation in dystonia: State of art and future directions.

When considering Deep Brain Stimulation (DBS) surgical treatment of dystonia syndromes, it is important to consider multiple aspects of the disease and its presentation. It is crucial to know if the dystonia is idiopathic, inherited or acquired as well as focal, segmental or generalised. Careful phenotyping of idiopathic as well as inherited dystonias and accurate diagnosis of acquired dystonias informs the decision-making process for patients and clinicians by providing them with useful predictors of outcomes of the proposed surgery. Here, we provided a review of the current literature, highlighted the areas where evidence is scarce and suggested future directions for research.

Integration of blood volume, blood pressure, heart rate and bioimpedance monitoring for the achievement of optimal dry body weight during chronic hemodialysis.

BACKGROUND: Achieving optimal dry body weight in hemodialysis is challenging. Clinical assessment alone is inadequate, and methods such as bioimpedance monitoring may be impractical for every patient treatment. Continuous blood volume monitoring, blood pressure and heart rate variability inform clinical decision-making, but integrated use of multiple methodologies to achieve dry weight and understand patient factors has not yet been described. METHODS: Nineteen chronic hemodialysis patients underwent thrice-weekly treatments for two weeks. Baseline hydration status and target weight were determined by bioimpedance. During subsequent treatments, ultrafiltration was adjusted and relative blood volume, blood pressure and pulse were recorded non-invasively. Bioimpedance was repeated to assess hydration. Response of variables to progressive change in weight was assessed and selected patients underwent additional autonomic function testing. RESULTS: Four distinct hemodynamic patterns emerged. Profile A: 4 patients demonstrated overhydration at baseline. With decreasing target, pulse and blood pressure remained stable while blood volume and bioimpedance demonstrated achievement of dry weight. Profile B: 8 patients demonstrated overhydration at baseline. With decreasing target, blood pressure remained stable while pulse increased. Profile C: 5 patients were overhydrated, but as weight decreased, blood pressure became unstable and heart rate failed to compensate. Further testing confirmed autonomic dysfunction. Profile D: 2 patients were dehydrated, and with increasing target demonstrated stable pulse and pressure, while blood volume and bioimpedance revealed achievement of dry weight. CONCLUSIONS: Integrating existing non-invasive, continuous monitoring during hemodialysis enabled achievement of dry weight and identified distinct profiles of the patients, some with autonomic dysfunction. This strategy may contribute to achieving optimum dry weight while improving cardiovascular tolerability of hemodialysis.

Acute pulmonary oedema: not always cardiogenic.

A patient presented with fulminant pulmonary oedema and required acute intubation and ventilation. There was no history of a prior cardiac disorder. As he was weaned from sedation, following stabilisation of his pulmonary status, neurological signs suggestive of brainstem dysfunction became apparent. Investigations showed infarcts in the posterior cerebral circulation secondary to a vertebral artery dissection. Neurogenic pulmonary oedema needs to be considered in any patient with fulminant pulmonary oedema without overt evidence or history of cardiac disease.

Management of fluid overload in congestive heart failure: learning from a case report.

A case of refractory fluid overload due to congestive heart failure and consequent renal insufficiency is reported. The case was approached multidisciplinarily, at the beginning with conservative and pharmacological therapy, subsequently with extracorporeal fluid removal in which a specific attention was payed to the maintenance of circulating blood volume and achievement of dry weight, and finally with chronic peritoneal dialysis as a maintenance therapy. The case seems to summarize the pathway of many patients seen initially in intensive care and cardiology departments and subsequently in nephrological wards.

Applause sign: screening utility for dementia and cognitive impairment.

OBJECTIVE: To examine the diagnostic utility of applause sign scores for the diagnosis of dementia and mild cognitive impairment. METHODS: Consecutive unselected new outpatient referrals to a dedicated cognitive disorders clinic over a 12-month period were administered the clapping test. Criterion diagnosis was by usual clinic assessment using standard diagnostic criteria, blind to applause sign score. RESULTS: Applause sign scores differed significantly (p < 0.001) between diagnostic groups (dementia, mild cognitive impairment, subjective memory complaint) and did not correlate with other cognitive screening instrument scores. Nearly three-quarters of those with an abnormal score had cognitive impairment. Applause sign score was specific but not sensitive for a diagnosis of cognitive impairment. CONCLUSION: The applause sign supports a diagnosis of dementia or cognitive impairment in high prevalence settings and may be useful in conjunction with other cognitive screening tests.

Effect of cyclosporine, mycophenolate mofetil, and their combination with steroids on apoptosis in a human cultured monocytic U937 cell line.

Transplant patient plasma produces an increased rate of mononuclear cell apoptosis despite a normal serum creatinine value. Immunosuppressive medications may be one factor that causes an altered apoptotic pattern. We evaluated the in vitro effects of various doses of cyclosporine, mycophenolate mofetil, and steroids on apoptosis of a cultured human monocytic U937 cell line, using estimates by fluorescence microscopy and annexin V assays. Increasing cyclosporine concentrations (100 to 800 ng/mL) progressively increased apoptosis rates (16% to 32%). The combination of steroid (0.01 microg/mL) and cyclosporine increased the apoptosis rate to 45%. Mycophenolate mofetil alone (0.3 microg/mL) led to an apoptosis rate of 34%. Therapeutic levels of mycophenolate mofetil from 3 to 7 microg/mL led to apoptosis rates from 56% to 67%. The combination of cyclosporine, steroid, and mycophenolate mofetil increased the rate of apoptosis to 95%. Immunosuppressive therapy may contribute to the high rate of apoptosis observed among mononuclear cells of transplanted patients. This effect may alter patient susceptibility to infections and contribute to a unique mechanism of immunosuppression.

Sequential convective therapies (SCT): a prospective study on feasibility, safety, adequacy and tolerance of on-line hemofiltration and hemodiafiltration in sequence.

Sequential dialysis techniques (i.e pure ultrafiltration followed by dialysis) have been used in the past, due to their capability to remove large volumes of fluids without inducing hemodynamic instability. The disadvantages of inadequate efficiency and lack of technology lead to the decline of such methods. Hemofiltration (HF) and hemodiafiltration (HDF) are recently being utilized in a greater proportion thanks to on-line fluid preparation systems. Each process (HF and HDF) has its own benefits in the removal of small, medium and high-molecular weight substances and in hemodynamic stability. Sequential convective therapies (SCT) such as hemofiltration-hemodiafiltration in sequence (HF-HDF) may combine the benefits and eliminate the disadvantages of each method and should be studied in order to explore their potential application in modern dialysis. Furthermore they can be easily applied nowadays, due to the development of new sophisticated dialysis machines. In order to evaluate the feasibility, safety, efficiency and tolerance of different SCT methods we studied 3 schedules: SCT1: 1h pre-dilution HF followed by 3h of post-dilution HDF (in the HF mode we lost 25% of the total fluid that had to be removed). SCT2: 1h pre-dilution HF followed by 3h of post-dilution HDF (in the HF mode we lost 50% of the total fluid that had to be removed). SCT3: 2h pre-dilution HF followed by 2h of post-dilution HDF (in the HF mode we lost 50% of the total fluid that had to be removed). We studied 6 chronic hemodialysis patients using the same machine (AK200 ULTRA), with on-line fluid preparation system and the same type of dialyzer (Polyflux 210). SCT schedules were compared to on-line HF, on-line HDF and high flux dialysis performed with the same dialyzers. The treatments resulted safe, easy, feasible and well tolerated with an improved hemodynamic response to high volume convective therapies. Adequacy of treatment was satisfactory in all SCT schedules while middle molecular weight solute clearance and removal resulted higher in treatments with higher convective component. SCT might represent an interesting option for the future especially in patients with hemodynamic instability and requirements for interventions during treatment.

[Rationale for the use of extracorporeal treatments for sepsis].

Sepsis is the leading cause of disability and mortality among critical patients; moreover, it causes high economic expenditures. Although very much is known about the pathophysiology of this condition and its mediators despite great investments directed to its control, mortality rates remain high. Recent treatment manuals emphasize the value of early goal-oriented therapy and also point to the high efficacy of activated protein C. Extracorporeal blood clearance may potentially become a new approach to treating this condition. There are reports on its positive clinical results that are likely associated with the effective removal of septic mediators. Human and animal studies, few and rather alike as they are, have yielded promising results. It is evident that the use of these procedures is justified; however, their efficiency in sepsis requires large-scale, correctly conducted studies.

Extracorporeal treatments in sepsis: are there new perspectives?

Sepsis continues to provide a major challenge to clinicians. Despite vast advancements achieved in the understanding of its pathways and mechanisms, the incidence of sepsis is increasing and the mortality and morbidity rates remain high, generating a considerable burden to health budgets worldwide. Unfortunately, no definitive therapy yet exists that can successfully treat sepsis and its complications. At variance with targeting single mediators, therapeutic intervention aimed at the non-selective removal of pro- and anti-inflammatory mediators seems a rational concept and a possible key to successful extra-corporeal therapies. A further advantage may lie in the continuous nature of such therapy. With such continuous therapy, sequentially appearing peaks of systemic mediator overflow may be attenuated and persistently high plasma levels reduced. This theoretical framework is proposed as the underlying biological rationale for a series of innovative modalities in sepsis. In this editorial, we will review recent animal and human trials which lend support to this concept. We will also review the importance of treatment dose during continuous renal replacement therapy as a major factor affecting survival in critically ill patients with acute renal failure. We will also review novel information related to other blood purification techniques using largo pore membranes or plasma filtration with adsorbent perfusion. Although these approaches are still in the early stages of clinical testing, they are conceptually promising and might represent an important advance.

Continuous flow peritoneal dialysis: a new double lumen catheter.

Continuous flow peritoneal dialysis (CFPD) is a therapy originally utilized in the sixties. It was then abandoned because of technical reasons, but, today, a new interest in this technique is emerging, because of new technical solutions and new hardware capabilities. CFPD is a peritoneal dialysis technique in which a certain amount of fluid is maintained in the peritoneal cavity, while a continuous inflow and outflow is provided via twin catheters or through a double lumen catheter. In this paper a new double lumen catheter is presented. The catheter is characterized by the presence of a diffuser in the inflow lumen, while a standard coiled shape characterizes the outflow lumen. The diffuser allows the use of high dialysate flows without peritoneal damage and with an excellent distribution of the fluid. The other feature of the catheter is the removable hub which allows for an easy subcutaneous tunneling of the catheter with a subsequent connection to the y segment. The special shape also guarantees a minimum recirculation during treatment. Data obtained in the first implanted catheter showed a progressive increase in small solute clearances in relation to an increase of the flow and the tidal volume in the peritoneal cavity. In particular, urea clearances up to 48 ml/min and creatinine clearances up to 39 ml/min were obtained. No major complications were observed after one year of use of the catheter.

Nephrotic syndrome and plasmapheresis.

We studied 15 patients suffering from nephrotic syndrome (NS) in bioptically-accertained primary and secondary glomerulopathies responding poorly to the common pharmacological treatment. They were monitored for one year by assessing their immunological and kidney functionality parameters, especially proteinuria. The patients underwent 3 apheretic sittings using the cascade double-filtration technique. After the third apheretic sitting the patients received metilprednisolone 300 mg/m2. This therapy was repeated every month for 6 months. At the end of the apheretic cycle it was shown that all patients had responded well to the therapy with a dramatic decrease in proteinuria, maintenance and/or recuperation of kidney functionality and improvement of lipidic asset; these data remained unchanged over time. Considering our preliminary results, we believe that therapeutic apheresis has a precise function in refractory nephrotic syndrome and, in particular, we propose the use of the cascade double-filtration technique.

First clinical trial for a new CRRT machine: the Prismaflex.

A new CRRT machine has been designed to fulfill the expectations of nephrologists and intensivists operating in the common ground of critical care nephrology. The new equipment is called "Prismaflex" (Gambro-Dasco, Mirandola, Modena) and it is the natural evolution of the Prisma machine that has been utilized worldwide for CRRT in the last decade. We performed a preliminary "alfa trial" to establish usability, flexibility and realiability of the new device. Accuracy was also tested by recording various operational parameters during different intermittent and continuous renal replacement modalities. Forty-one runs were conducted on 13 patients and the difference between delivered and prescribed parameters was always lower than 2%. We concluded that the new Prismaflex is a well designed new machine for CRRT and can be safely and effectively utilized in the critical care nephrology setting.

Pulse high volume hemofiltration.

The sepsis syndrome is the most common cause of acute renal failure and multiple organ dysfunction in critically ill subjects and continues to have an alarmingly high mortality. Normal immune homeostasis is interrupted by a complex storm of inflammatory mediators responsible for the deleterious effects. Extracorporeal blood purification techniques can confer benefits in sepsis by proven non-specific removal of these mediators (pro- or anti-inflammatory), and provide a logical and adequate approach to treat this syndrome. High volume hemofiltration (HVHF) has had the most dramatic effect conferring benefits in hemodynamics, reduction in vasopressor doses and improvement in survival. "Pulse HVHF" is the latest approach which may offer the most efficient results: a daily schedule of 6-8 hours followed by standard CVVH. This paper describes the rationale and potential of this technique. Reliability and tolerance of this technique and biological effects are described.

Caspase-3 and -8 activation and cytokine removal with a novel cellulose triacetate super-permeable membrane in an in vitro sepsis model.

Pro-apoptotic molecules are generated during sepsis which may be responsible for alteration of organ function in sepsis. Removal of systemic apoptotic activity may affect recovery from sepsis. Current high flux membranes might not be sufficiently permeable to eliminate pro-apoptotic factors. We evaluated the elimination of pro-apoptotic factors induced by LPS in human whole blood by a super-permeable cellulose triacetate membrane (SUREFLUX FH 150, Nipro, Osaka, Japan) in comparison to a standard high flux cellulose triacetate membrane (UT 700, Nipro, Osaka, Japan) and a polyethersulfone plasmafilter (Bellco, Mirandola Italy) in an in vitro blood circulation. We spiked human whole blood with lipopolysaccharide from Escherichia coli (Serotype 026-86, 10 mg/ml), incubated it for 3 hours to allow cytokine generation and recirculated it at 300 ml/min for 3 hours. The UF line was first returned to the blood module at 10 min. After this, the UF was drained from 10 to 60 min at a rate of 1000 ml/h. Zero balance was obtained by re-infusion of bicarbonate buffered hemofiltration fluid. Apoptosis was assessed on U937 monocytes (incubated with plasma or ultrafiltrate) by fluorescence microscopy dyes (Hoechst 33342, propidium iodide) and annexin V flow cytometry. Caspase-3 and Caspase-8 activity was assessed on the recirculated blood monocytes by spectrophotometric methods. IL-2, IL-10 and TNFalpha were determined by commercially available ELISAs. Sieving coefficients and clearances were determined for the different cytokines. Caspase-3 and Caspase-8 were activated by LPS and remained either stable or increased during in vitro circulation. Apoptosis activity of U937 cells, when incubated with the ultrafiltrate, increased in parallel with arterial plasma values (for Uf: UT700 = 23.1%; Sureflux FH150 = 42.5%). However, by 60 min the apoptotic activity recorded with the ultrafiltrate was reduced to the levels of arterial plasma (for Uf: UT700 = 19.8%; Sureflux FH150 = 11.2%). Sieving coefficients in the super-permeable membrane were significantly higher for all measured cytokines in comparison to the standard high flux membrane (e.g. TNFalpha 0.72 vs 0.03 p < 0.001) and close to the values observed for the plasmafiltration membrane. Nevertheless protein losses measured by albumin leakage were much lower with the Sureflux filter in comparison to the plasmafilter. In conclusion, pro-apoptotic factors can be eliminated by dialytic membranes with the removal rate maximized by using super high flux dialysers which may represent a compromise between hemofiltration and plasmafiltration membranes.

[Plasmapheresis combined with pharmacology in the treatment of lupus nephritis: a new therapeutic protocol]. / La plasmaferesi associata alla terapia farmacologica nel trattamento della nefrite lupica: nuovo protocollo terapeutico.

Systemic Lupus Erythematosus (SLE) is a pathology of unknown cause, characterized by tissue and cellular damage, secondary to production of autoantibodies and to deposition of immunocomplexes. Lupus nephritis is one of the most common complications of SLE. Our purpose is to propose a therapeutic protocol for patients suffering from Lupus nephritis. This consists of Plasmapheresis associated with pharmacological therapy so that dosage of immunosuppressors can be reduced and consequently also the side effects of the pharmacological therapy.

[Efficacy of recombinant erythropoietin on the quality of life in patients over 60 years of age undergoing hemodialysis]. / Efficacia dell'eritropoietina ricombinante sulla qualità di vita in pazienti emodializzati ultrasessantenni.

We followed for a period of six months, 54 patients of over 60 years old, submitted to hemodialitic treatment. We gave human recombinant erythropoietin, average dosage 50 UI/Kg subcutaneously on alternative days, folic acid and iron supplements together with a proteic supply of 1.2 g/Kg/die (35 Kcal/Kg). The medullary response has been monitored with hematochemical tests; blood pressure and nutritional conditions have been evaluated. Furthermore, the patients were given a questionnaire to evaluate their quality of life. At the end of the follow up, 50 patients responded positively to therapy. These patients showed an increase of RBC (from 2,789,780 +/- 259,310 to 3,313,110 +/- 472,780 p < 0.001) of HCT (from 21.86% +/- 2.16% to 27.18 +/- 2.74% p < 0.0001) and of Hb (from 7.72 +/- 1.12 g/dl to 9.28 +/- 0.98 g/dl p < 0.006). Total protein and albumin increased too. Furthermore they showed a progressive increase of "performance status". Our results confirm efficacy of erythropoietin in the treatment of anemia in elderly hemodialized patients.

[Comparative study of the modification of arterial pressure in adult and aged subjects treated with hemofiltration. Preliminary results]. / Studio comparativo delle modificazioni della pressione arteriosa in soggetti adulti ed anziani in trattamento dialitico con tecnica di emofiltrazione. Risultati preliminari.

Haemodynamics modifications in 49 patients divided in two groups consisting of 21 young people (average age 43 +/- 12 yrs.) and 28 elderly people (average age 72 +/- 7 yrs.) who have undergone at least three treatments with haemofiltration for congestive cardiac decompensation and chronic renal failure have been evaluated. Systolic and diastolic blood pressure and heart rate have been monitored for each patient in a length of time of iT, T30 min., T60 min., fT. The results show a statistically significant reduction of the systolic pressure during the time interval iT-T30 min. in subjects over 65, contrary to the control group. Such preliminary results can be justified by the haemodynamic modifications correlated to the elderly process. In any case the hypothesis cited by the authors need further testing even if confirming the indication of the dialytic treatment on patients over 65 through haemofiltration techniques.