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.

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.

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.

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.

Successful use of sodium hypochlorite pack plus systemic and local antibiotic therapy for the treatment of pseudomonas infection of peritoneal dialysis catheter exit-site.

Peritoneal catheter exit-site and tunnel infections remain critical problems in patients undergoing peritoneal dialysis. Catheter-related peritonitis occurs in about 20% of patients and exit-site infections are responsible for catheter removal in more than one-fifth of the cases. For the last 2 years in the Department of Nephrology, San Bortolo Hospital, Vicenza, Italy, we have been treating exit-site infections caused by Pseudomonas with sodium hypochlorite packs as well as systemic and local antibiotic therapy. Considering the encouraging results obtained on Pseudomonas infection, we decided to utilize the same schedule for the treatment of exit-site infections caused by other germs which are generally difficult to eradicate to prevent peritonitis and catheter removal. Between 2003 and 2004, 10 patients contracted infection of the exit-site. All patients underwent a swab test because of the reddening and the purulent secretion of the exit-site. The swab resulted positive for Pseudomonas in 7 patients, Corynebacterium sp. in 2 patients, and Candida albicans in 1 patient. All patients were treated with systemic antibiotic therapy or antifungal therapy, local sodium hypochlorite 50% packs. After 15 days all patients were submitted to a swab test of the exit site. In all patients, the swab test resulted negative after 15 days and 1 month, and they could continue peritoneal dialysis. This procedure avoided peritoneal catheter removal and temporary switch to hemodialysis in all patients with exit site infection. The mechanism of action is related to the wide antimicrobial spectrum and the rapid action of sodium hypochlorite possibly creating a protective barrier on the exit-site.

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.

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.

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.

[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.

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.

Sequential hemofiltration-hemodiafiltration technique: all in one?

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 the inadequate dialysis and the lack of technology lead to the decline such methods. Hemofiltration (HF) and hemodiafiltration (HDF) are recently being utilized in a greater proportion thanks to the 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 the hemodynamic stability. Sequential hemofiltration/ hemodiafiltration (SHF/HDF), may combine the benefits and eliminate the disadvantages of each method. Furthermore they can be easily applied nowadays, due to the development of new high technological hemodialysis machines. In order to evaluate the feasibility and the effects of SHF/HDF we studied 7 chronic hemodialysis patients (6 months of treatment with SHF/HDF switched to 6 months of SHDF/HF), using the same machine (AK200 ULTRA), with on line fluid preparation system and the same type of dialyzer (Polyflux 210). The feasibility of such techniques (SHF/HDF or vice versa) resulted excellent. All sessions left the patients in a condition of well-being making fulltime work. No difference was observed between the different period of treatment, but a reduction in pre value was observed in calcium-phosphorous product, C-reactive protein and beta2-microglobulin, at the end of the sequential techniques. SHF/HDF therapy is a very promising technique. Further studies are needed to better explore the potential of such a therapeutic approach in the quality of life, the hemodialysis adequacy and the hemodynamic stability of our patients.

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.

Continuous renal replacement technology: from adaptive devices to flexible multipurpose machines.

OBJECTIVE: To review the evolution of technologies in the development of renal replacement therapies. DATA SOURCES: Articles and published reviews on renal replacement therapies. SUMMARY OF REVIEW: Continuous arterio-venous haemofiltration (CAVH) was the first continuous renal replacement technique capable of overcoming the traditional haemodialysis-related side effects, making possible the treatment of critically ill patients safely and with less physiological instability. The evolution of technology and the progress experienced in intensive care units (ICUs) has made it possible to start renal replacement therapy programs in the absence of a chronic dialysis facility or a trained nephrological team. Initial limitations and draw-backs of CAVH, stimulated the ICU staff to explore new avenues for better therapy. Extracorporeal therapies are today a routine experience in the ICUs: continuous renal replacement therapies are a broadly accepted treatment for acute renal failure. Furthermore, alternative indications for extracorporeal blood circulation (e.g. sepsis, liver failure, congestive heart failure, drug intoxications, hyperthermia, immuno-mediated syndromes) are becoming more and more popular. The ideal machine has yet to be completed, but progress has occurred and has opened a new era for critical care nephrology and the further expansion of blood purification technology in the ICU. CONCLUSIONS: Technical advances in renal replacement therapies have increased their functionality (i.e. used in hepatic failure, sepsis, cardiac failure and immuno-mediated syndromes), are easier to operate and have less side-effects compared with their standard extracorporeal counterparts. Further improvements may see them become a routine part in the management of the critically ill patient.

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.