Guideline-directed medical therapy in severe heart failure with reduced ejection fraction: An analysis from the HELP-HF registry.

AIM: Persistent symptoms despite guideline-directed medical therapy (GDMT) and poor tolerance of GDMT are hallmarks of patients with advanced heart failure (HF) with reduced ejection fraction (HFrEF). However, real-world data on GDMT use, dose, and prognostic implications are lacking. METHODS AND RESULTS: We included 699 consecutive patients with HFrEF and at least one 'I NEED HELP' marker for advanced HF enrolled in a multicentre registry. Beta-blockers (BB) were administered to 574 (82%) patients, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers or angiotensin receptor-neprilysin inhibitors (ACEi/ARB/ARNI) were administered to 381 (55%) patients and 416 (60%) received mineralocorticoid receptor antagonists (MRA). Overall, ≥50% of target doses were reached in 41%, 22%, and 56% of the patients on BB, ACEi/ARB/ARNI and MRA, respectively. Hypotension, bradycardia, kidney dysfunction and hyperkalaemia were the main causes of underprescription and/or underdosing, but up to a half of the patients did not receive target doses for unknown causes (51%, 41%, and 55% for BB, ACEi/ARB/ARNI and MRA, respectively). The proportions of patients receiving BB and ACEi/ARB/ARNI were lower among those fulfilling the 2018 HFA-ESC criteria for advanced HF. Treatment with BB and ACEi/ARB/ARNI were associated with a lower risk of death or HF hospitalizations (adjusted hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.48-0.84, and HR 0.74, 95% CI 0.58-0.95, respectively). CONCLUSIONS: In a large, real-world, contemporary cohort of patients with severe HFrEF, with at least one marker for advanced HF, prescription and uptitration of GDMT remained limited. A significant proportion of patients were undertreated due to unknown reasons suggesting a potential role of clinical inertia either by the prescribing healthcare professional or by the patient. Treatment with BB and ACEi/ARB/ARNI was associated with lower mortality/morbidity.

Clinical and prognostic implications of heart failure hospitalization in patients with advanced heart failure.

BACKGROUND: Hospitalization is associated with poor outcomes in patients with heart failure, but its prognostic role in advanced heart failure is still unsettled. We evaluated the prognostic role of heart failure hospitalization in patients with advanced heart failure. METHODS: The multicenter HELP-HF registry enrolled consecutive patients with heart failure and at least one high-risk 'I NEED HELP' marker. Characteristics and outcomes were compared between patients who were hospitalized for decompensated heart failure (inpatients) or not (outpatients) at the time of enrolment. The primary endpoint was the composite of all-cause mortality or first heart failure hospitalization. RESULTS: Among the 1149 patients included [mean age 75.1 ±â€Š11.5 years, 67.3% men, median left ventricular ejection fraction (LVEF) 35% (IQR 25-50%)], 777 (67.6%) were inpatients at the time of enrolment. As compared with outpatients, inpatients had lower LVEF, higher natriuretic peptides and a worse clinical profile. The 1-year rate of the primary endpoint was 50.9% in inpatients versus 36.8% in outpatients [crude hazard ratio 1.70, 95% confidence interval (CI) 1.39-2.07, P < 0.001]. At multivariable analysis, inpatient status was independently associated with a higher risk of the primary endpoint (adjusted hazard ratio 1.54, 95% CI 1.23-1.93, P < 0.001). Among inpatients, the independent predictors of the primary endpoint were older age, lower SBP, heart failure association criteria for advanced heart failure and glomerular filtration rate 30 ml/min/1.73 m2 or less. CONCLUSION: Hospitalization for heart failure in patients with at least one high-risk 'I NEED HELP' marker is associated with an extremely poor prognosis supporting the need for specific interventions, such as mechanical circulatory support or heart transplantation.

The recovery of reaching movement in breast cancer survivors: two different rehabilitative protocols in comparison.

BACKGROUND: Breast cancer (BC) is the most common cancer in women in the developed world. The about the sequelae of surgery, especially in case of mastectomy or modified radical mastectomy is grown. Nowadays it is important choose appropriate exercise programs to allow recovery in "quantity" but also in "quality" of the movement of the operated upper limb. AIM: The aim of this study was to verify whether specific exercises for the scapula may induce changes in fluidity of the reaching movement. DESIGN: Randomized control-trial double-blind study. SETTING: Exercise training laboratory and gait analysis laboratory. POPULATION: Sixty-three breast cancer survivors were enrolled. METHODS: Participants randomized to single rehabilitative treatment (ST), or to group rehabilitative treatment (GT). VAS, DASH and a biomechanical evaluation of upper limb were performed for each group before treatment (T0=baseline), at the end rehabilitative treatment (T1) and after three months of follow-up (T2). RESULTS: Respect within group analysis, in the ST and in the GT, for VAS an improvement along evaluation times were observed, respectively at T0 to T1 and at T0 to T2 (P<0.001) without a statistically significant difference between groups. At the same, for the DASH, the results showed the same trend without a statistically significant difference between groups. For biomechanical parameters, at T2 velocity was statistically significantly greater in the ST than in the GT (P=0.029) in contrast with the duration, that was statistically significantly greater in the GT than in the ST (P=0.010). CONCLUSIONS: Both protocols are effective in reducing pain and for functional recovery of the upper limb. The adoption of a non-intensive rehabilitation program should be implemented at least in the first year after the operation, with the adoption of specific myofascial exercises on the scapulo-thoracic joint with better results in the "qualitative" recovery of the achievement. CLINICAL REHABILITATION IMPACT: Our study emphasizes the importance of rehabilitation in BC survivors after mastectomy, even during the course of radiotherapy and chemotherapy and the adoption of specific myofascial exercises on the scapulo-thoracic joint and specific exercises of muscular stretching on the pectoral muscle. Therefore, the proposed rehabilitation protocol must be "clipped" and "integrated" according to the specific objectives for each individual patient.

The sequelae of mastectomy and quadrantectomy with respect to the reaching movement in breast cancer survivors: evidence for an integrated rehabilitation protocol during oncological care.

BACKGROUND: Breast cancer (BC) is the most common cancer among women in developed countries. Several types of surgical interventions are commonly used in BC, such as mastectomy and quadrantectomy, followed by radiation or not. Today, BC rehabilitation can help survivors obtain and maintain the highest physical, social, psychological, and vocational functioning possible, within the limits that are created by cancer and its treatments. OBJECTIVE: To verify, before and after a specific rehabilitation protocol treatment, the recovery of the fluidity of the reaching movement. METHODS: Patients after BC surgery were enrolled and assigned by cluster randomization into 2 groups through a block randomization list: mastectomy (Mas) and quadrantectomy (Quad). Evaluation scales (DASH and VAS) were administered, and biomechanical evaluations were performed for each group before treatment (T0 = baseline), at the end of the rehabilitative treatment (T1 = 12 sessions, 2/week), and after 3 months of follow-up (T2). RESULTS: Fifty-nine (Mas group = 29; Quad group = 30) after BC surgery were enrolled. VAS scores improved along the evaluation times at T0-T1 and T0-T2 (p < 0.001), without a statistically significant difference between groups. With regard to the normalized jerk, there was no significant interaction between time group (F = 2.029; p = 0.136). There was a significant decrease between T0-T1 and T1-T2 (F = 60.189; p < 0.001). Velocity improved significantly between T0-T1 and T1-T2 (F = 10.322; p < 0.001). There was a significant interaction for the elbow angle at the end of movement between time and group at T2 (F = 5.022; p = 0.029). CONCLUSION: The integrated, low-intensity, rehabilitative intervention is effective, even if it is not performed in the first period after BC surgery, without any difference between mastectomy and quadrantectomy.

The effect of aquatic physical therapy on patients with multiple sclerosis: A systematic review and meta-analysis.

BACKGROUND: The aquatic environment has unique properties, such a buoyancy, turbulence, hydrostatic pressure, and resistance, which can be used to gain a range of exercise benefits. During the last decade, hydrotherapy has spread in a very heterogeneous rehabilitation field. However, the efficacy of this kind of rehabilitation is not clear in scientific literature. The purpose of this study is to conduct a systematic review with meta-analysis to evaluate the qualitative and quantitative results of physical therapy treatments in an aquatic setting for individuals with Multiple Sclerosis. METHOD: PRISMA guidelines were used to carry out the systematic review and meta-analysis. Three bibliographic databases were searched: MEDLINE, PEDro, and the Cochrane Library. Papers included in the study have the following characteristics: (a) a randomized controlled trial design of research and (b) published in English. The quality of the clinical trials included were evaluated according to a Jadad score and through meta-analysis. RESULTS: After the elimination of duplicates, 116 records were screened. Among these, 11 Randomized Controlled Trials (RCTs) were included in the systematic review. Ten of these were involved in the meta-analysis. From the qualitative analysis, a larger number of studies were found with a high level of quality. Most of the results of the quantitative analysis were statistically significant (p< 0.05). CONCLUSION: Aquatic physical therapy is a valid means of rehabilitation for people with Multiple Sclerosis. The integration of this methodological approach with conventional physical therapy is recommended. Nevertheless, more studies, a larger number of participants, and short-, medium-, and long-term follow-up are required to confirm current results.

Physical Activity Scale for the Elderly: Translation, Cultural Adaptation, and Validation of the Italian Version.

OBJECTIVE: The aim of the study was to translate and culturally adapt the Physical Activity Scale for the Elderly into Italian (PASE-I) and to evaluate its psychometric properties in the Italian older adults healthy population. METHODS: For translation and cultural adaptation, the "Translation and Cultural Adaptation of Patient-Reported Outcomes Measures" guidelines have been followed. Participants included healthy individuals between 55 and 75 years old. The reliability and validity were assessed following the "Consensus-Based Standards for the Selection of Health Status Measurement Instruments" checklist. To evaluate internal consistency and test-retest reliability, Cronbach's α and Intraclass Correlation Coefficient (ICC) were, respectively, calculated. The Berg Balance Score (BBS) and the PASE-I were administered together, and Pearson's correlation coefficient was calculated for validity. RESULTS: All the PASE-I items were identical or similar to the original version. The scale was administered twice within a week to 94 Italian healthy older people. The mean PASE-I score in this study was 159±77.88. Cronbach's α was 0.815 (p < 0.01) and ICC was 0.977 (p < 0.01). The correlation with the BBS was 0.817 (p < 0.01). CONCLUSIONS: The PASE-I showed positive results for reliability and validity. This scale will be of great use to clinicians and researchers in evaluating and managing physical activities in the Italian older adults population.

Complications following endoscopic intracranial procedures in children.

BACKGROUND: The significant technological improvement of endoscopic instrumentation has allowed, in the last 10 years, a widespread diffusion of neuroendoscopic procedures. Nevertheless, severe, sometimes life-threatening, complications may occur during neuroendoscopic surgery, and the incidence and age specificity of complications in children have been underdescribed so far. MATERIALS AND METHODS: Complications recorded in a prospectively collected database of pediatric patients undergoing neuroendoscopic procedures were analysed; the medical histories of the patients and the surgical procedures were reviewed. RESULTS: Complications occurred in 32 out of 231 (13.8%) procedures performed for the management of obstructive hydrocephalus (137), multiloculated hydrocephalus (53), arachnoid cysts (29) and intraventricular tumors (12). Subdural hygroma occurred in 11 cases, seven requiring subdural shunting. In one of these cases, infection of the subdural space occurred and required a craniotomy. Cerebrospinal fluid (CSF) infection occurred in 11 cases. In one case, a frontal abscess developed and was managed with craniotomy. CSF leak occurred in nine cases, intraventricular haemorrhages in two, technical failures in seven, subcutaneous CSF collection (managed with lumbo-peritoneal shunt) in one, thalamic contusion and post-operative transient akinetic mutism in one. This patient suddenly died 6 months later, probably as a consequence of closure of the stoma. Two patients developed secondary compartmentalisation of the ventricles after complicated endoscopic third ventriculostomy. In nine cases, these complications were associated. Overall, no patient died after the procedure (operative mortality 0), one patient died 6 months after the procedure for unexplained events (sudden death rate 0.4%), and three patients presented permanent disability as a consequence of surgical complication (permanent morbidity 1.3%). CONCLUSIONS: Complication rate of neuro-endoscopic procedures is not negligible even in experienced hands. The majority are minor complications which do not affect the final outcome, but sporadically major events may occur, leading to significant problems in surgical management and, occasionally, to permanent disabilities. Careful selection of patients on pre-operative imaging studies and intensive training of surgeons are mandatory to improve results.

Neuroendoscopic treatment of multiloculated hydrocephalus in children.

OBJECT: The authors performed a retrospective analysis of data obtained in a series of 30 patients suffering from multiloculated hydrocephalus and treated endoscopically. The goal of the study was to evaluate the effectiveness of neuroendoscopic treatment as an alternative to the placement of multiple shunts to relieve intracranial hypertension, to simplify the shunt system, and to reduce the high rate of shunt revision. METHODS: The endoscopic procedures included intraventricular septum fenestration, aqueductoplasty, Monro foraminoplasty, and third ventriculostomy. The patients were divided into two groups: Group A included 23 children in whom a shunt was already in place at the time of endoscopy, and Group B included seven children in whom a shunt had never been placed. The control of hydrocephalus by a single shunt placement or the absence of a shunt was achieved in 25 (83.3%) of 30 children. In Group A, five children no longer had shunts, 14 needed a single shunt, three required two shunts, and one required three shunts. The mean preendoscopy shunt revision rate in this group decreased from 2.07/year to 0.35/ year following the endoscopic procedure. Seven patients required endoscopic reoperations (endoscopic reoperation rate 0.31/year, total reoperation rate [shunt revisions plus endoscopic reoperation] 0.66/year). In Group B, three children did not require shunts, three needed a single shunt, and one required two shunts. Two patients required repeated endoscopic surgery (endoscopic reoperation rate 0.19/year), and two patients required shunt revisions (shunt revision rate 0.07/year) (total operation rate 0.26/year). CONCLUSIONS: Neuroendoscopic procedures are a valid alternative to shunt revision in the management of multiloculated hydrocephalus. Early diagnosis comprising close monitoring with high-resolution magnetic resonance imaging and early treatment are the keys of success.

Neuroendoscopic management of interhemispheric cysts in children.

OBJECT: Interhemispheric arachnoid cysts are very rare, and they are often associated with complex brain malformations such as corpus callosum agenesis and hydrocephalus. Debate remains concerning the proper management of these lesions. Placement of shunts and microsurgical marsupialization of the cyst are the traditional options. Using endoscopic methods to create areas of communication between the cyst, the ventricular system, and/or the subarachnoid space is an attractive alternative to the use of shunts and microsurgery. METHODS: Between 2000 and 2005, seven consecutive pediatric patients with interhemispheric arachnoid cysts underwent neuroendoscopic treatment involving cystoventriculostomy in two patients, cystocisternostomy in two, and cystoventriculocisternostomy in three. There were three cases of associated hydrocephalus, six cases of corpus callosum agenesis, and one case of corpus callosum hypogenesis. The follow-up period ranged from 12 to 49 months (mean 31.6 months). Endoscopic procedures were completely successful in all but two patients. In one of the remaining two patients, a repeated endoscopic cystocisternostomy was performed with success because of closure of the previous stoma. In the other, a subcutaneous collection of cerebrospinal fluid (CSF) was managed by insertion of an lumboperitoneal shunt. A subdural collection of CSF developed in three patients; it was treated with insertion of a subduroperitoneal shunt in one patient and managed conservatively in the other two patients, resolving spontaneously without further treatment. Neurodevelopmental evaluation performed in six patients showed normal intelligence (total intelligence quotient [IQ] > 80) in three patients, mild developmental delay (total IQ 50-80) in two, and severe developmental delay (total IQ < 50) in one. CONCLUSIONS: Endoscopic treatment of interhemispheric cysts can be considered a useful alternative to traditional treatments, even if some complications are to be expected, such as subdural or subcutaneous CSF collections and CSF leaks due to thinness of cerebral mantle and to the often-associated multifactorial hydrocephalus.

The role of transventricular neuroendoscopy in the management of craniopharyngiomas: three patient reports and review of the literature.

BACKGROUND: Management of craniopharyngiomas is problematic and often requires multimodal protocols. In the last decade neuroendoscopy has been increasingly used in the management of these lesions. PATIENT REPORTS: We report three cases of craniopharyngiomas in which various endsocopic procedures were performed. In the first case the endoscopic approach alone allowed the gross total removal of an intraventricular craniopharyngioma; in the second case the endoscopic fenestration of a cystic intraventricular craniopharyngioma allowed long-term control of the tumor with no further treatment; in the third case endoscopic fenestration and drainage of the cystic part allowed collapse of the cyst with resolution of mass effect on the visual pathway and control of hydrocephalus. The patient later underwent microsurgical removal of the solid portion of the tumor. CONCLUSIONS: Neuroendoscopy has shown great versatility in the management of intra/paraventricular craniopharyngiomas. It can be used alone to achieve gross total removal or marsupialization of cystic tumors, or, more often, in association with additional therapies, such as microsurgery, radiosurgery or intracavitary drug administration.

Endoscopic aqueductoplasty and placement of a stent in the cerebral aqueduct in the management of isolated fourth ventricle in children.

OBJECT: In this study the authors conducted a retrospective evaluation of the effectiveness of endoscopic aqueductoplasty, performed alone or accompanied by placement of a stent, in the treatment of an isolated fourth ventricle (IFV) in seven patients afflicted with loculated hydrocephalus after a hemorrhage or infection. METHODS: Seven children with symptomatic IFV and membranous aqueductal stenosis underwent endoscopic aqueductoplasty alone or combined with placement of a stent in the cerebral aqueduct. The mean age of the patients at the time of surgery was 10 months. The mean duration of follow up was 26 months. In all patients a supratentorial shunt had already been implanted, and in five patients neuroendoscopy had already been performed because other isolated compartments had been present inside the ventricular system. Aqueductoplasty alone was performed in three patients and aqueductoplasty and aqueductal stent placement in four. A precoronal approach was performed in five patients and a suboccipital approach in two. Signs and symptoms of intracranial hypertension resolved in all cases. Stent placement was successful in all five cases, resulting in clinical and neuroimaging-confirmed improvements in the IFV. Restenosis of the aqueduct occurred in two patients in whom stents had not been placed. In one of these patients restenosis was managed by an endoscopic procedure, during which the aqueduct was reopened and a stent implanted; in the other patient a shunt was placed in the fourth ventricle. Hydrocephalus was controlled by a single shunt in six cases (86%) and by a double shunt in one case. CONCLUSIONS: Endoscopic placement of a stent in the aqueduct is more effective in preventing the repeated occlusion of the aqueduct than aqueductoplasty alone and should be indicated as the initial treatment in each case of compatible anatomy.

Intracranial pressure monitoring and lumbar puncture after endoscopic third ventriculostomy in children.

OBJECTIVE: The aim of this study is to analyze changes in intracranial pressure (ICP) after endoscopic third ventriculostomy (ETV) performed in children affected by noncommunicating hydrocephalus. METHODS: ICP was continuously recorded for an average of 7 days in 64 children who underwent 68 ETVs for obstructive triventricular hydrocephalus of various etiology. In the first group (44 children), ETV was performed as the primary treatment; in the second group (20 children), the patients presented with shunt malfunction and underwent ETV and shunt removal. Three of the patients in the second group were reoperated for obstruction of the stoma: two were reoperated once and one was reoperated twice. RESULTS: ICP changes after ETV were not homogeneous and varied according to etiology: the highest values were observed in patients affected by posterior fossa tumors and the lowest values were seen in patients operated on during shunt malfunction and who had their shunt removed. After 31 procedures (45.6%), ICP remained normal (< 20 mmHg) for the entire duration of the monitoring. After 37 procedures (54.5%), ICP was persistently high on Day 1 (mean, 29.7) and decreased very slowly in the subsequent days, remaining high for 2-9 days (mean, 4.5). After 20 of the 37 procedures with high postoperative ICP, patients presented symptoms of intracranial hypertension that resolved, in most of the cases, with one or two lumbar punctures. Lumbar puncture was noted to be effective in bringing about fast normalization of the ICP and resolution of the symptoms. In 13 patients (19.1%), ETV failed and a ventriculoperitoneal shunt was implanted. After four procedures, the stoma obstructed and the patients were treated, reopening the stoma. Postoperative ICP was not statistically significant higher in the patients in whom ETV failed. CONCLUSION: The high ICP observed in a group of patients in the early postoperative days is probably related to the slow permeation of the subarachnoid spaces by the cerebrospinal fluid flowing out of the third ventriculostomy. Management of intracranial hypertension after ETV remains a matter of controversy. The role of the lumbar puncture in the faster normalization of the ICP is examined in this article. By increasing the compliance and the buffering capacities of the spinal subarachnoid spaces, it probably decreases the cerebrospinal fluid outflow resistance from the ventricular system, facilitating the decrease of the ventricular volume and allowing faster permeation of the intracranial subarachnoid spaces. High postoperative ICP can account for persistent symptoms of intracranial hypertension and ventricular dilatation on computed tomographic scans after third ventriculostomy. A cycle of one to three lumbar punctures should always be performed in patients who remain symptomatic and who show increasing ventricular dilatation after ETV, before ETV is assumed to have failed and an extracranial cerebrospinal fluid shunt is implanted.

Current state and future development of intracranial neuroendoscopic surgery.

Since the introduction of the modern, smaller endoscopes in the 1960s, neuroendoscopy has become an expanding field of neurosurgery. Neuroendoscopy reflects the tendency of modern neurosurgery to aim towards minimalism; that is, access and visualization through the narrowest practical corridor and maximum effective action at the target point with minimal disruption of normal tissue. Transventricular neuroendoscopy allows the treatment of several pathologies inside the ventricular system, such as obstructive hydrocephalus and intra-/paraventricular tumors or cysts, often avoiding the implantation of extracranial shunts or more invasive craniotomic approaches. Endoscopic endonasal transphenoidal surgery allows the treatment of pathologies of the sellar and parasellar region, with the advantage of a wider vision of the surgical field, less traumatism of the nasal structures, greater facility in the treatment of possible recurrences and reduced complications. However, an endoscope may be used to assist microsurgery in virtually any kind of neurosurgical procedures (endoscope-assisted microsurgery), particularly in aneurysm and tumor surgery. Basic principles of optical imaging and the physics of optic fibers are discussed, focusing on the neuroendoscope. The three main chapters of neuroendoscopy (transventricular, endonasal transphenoidal and endoscope-assisted microsurgery) are reviewed, concerning operative instruments, surgical procedures, main indications and results.

Endoscopic third ventriculostomy in the treatment of hydrocephalus in posterior fossa tumors in children.

OBJECT: The purpose of the present study is to assess the effectiveness of endoscopic third ventriculostomy (ETV) in children with hydrocephalus related to posterior fossa tumors. METHODS: Between September 1999 and December 2002, 63 children with posterior fossa tumors were treated at Santobono Hospital in Naples, Italy. Twenty-six patients had severe hydrocephalus. In order to relieve intracranial hypertension before tumor removal, 20 were treated with ETV, and 6 with ventriculo-peritoneal (VP) shunts. Twenty patients with mild hydrocephalus were treated with diuretics, corticosteroid agents, and early posterior fossa surgery, and 17 patients who did not have hydrocephalus were treated by elective posterior fossa surgery. Another 4 ETV were performed in the management of postoperative hydrocephalus. RESULTS: Preoperative ETV procedures were technically successful. One was complicated by intraventricular bleeding. The successful 19 preoperative ETV resolved intracranial hypertension before posterior fossa surgery in all cases. Three of these 19 patients developed postoperative hydrocephalus and were treated by VP shunt insertion after posterior fossa surgery. Out of the 4 ETV performed after posterior fossa surgery, only 2 were successful, both when the shunt malfunctioned. CONCLUSIONS: Endoscopic third ventriculostomy should be considered as an alternative procedure to ventriculo-peritoneal shunting and external ventricular draining for the emergency control of severe hydrocephalus caused by posterior fossa tumors, since it can quickly eliminate symptoms, and hence, can delay surgery scheduling if required. Even though ETV does not prevent postoperative hydrocephalus in all cases, it does protect against acute postoperative hydrocephalus due to cerebellar swelling. In addition, it eliminates the risks of cerebrospinal fluid (CSF) infection related to external drainage and minimizes the risk of overdrainage because it provides more physiological CSF drainage than the other procedures. Since postoperative hydrocephalus is very often physically obstructive, ETV should always be considered a possible treatment procedure.

Second-line chemotherapy with the association of liposomal daunorubicin, carboplatin and etoposide in children with recurrent malignant brain tumors.

Progressive or recurrent high-grade gliomas are characterized by a very poor prognosis, and the relevance of second-line chemotherapy is still unassessed. Although it has been reported that liposomal anthracyclines and carboplatin show some activity in these patients, their association has never been investigated. We have treated six children with recurrent high-grade glioma after surgery, radiotherapy and chemotherapy, and one child with progressive teratoid/rhabdoid tumor with the combination of liposomal daunorubicin and carboplatin plus etoposide. Five out of seven children showed a major response and the 29 month progression-free survival was 38%. The above regimen was feasible and children showed only little and transient hematological toxicity. In our opinion, these results justify further investigation of the above combination chemotherapy for recurrent or progressive malignant brain tumors in children.

Aqueductal stenosis 9 years after mumps meningoencephalitis: treatment by endoscopic third ventriculostomy.

INTRODUCTION: Hydrocephalus due to aqueductal stenosis following mumps meningoencephalitis is a rare condition, reported only in 16 cases in the literature. The pathogenetic role of the mumps virus in inducing aqueductal stenosis has been demonstrated experimentally in animal models and clinically proven in a few cases. Although obstructive in nature, the post-infectious etiology raises the question as to whether third ventriculostomy is the appropriate treatment. PATIENT: We report a case of hydrocephalus due to pure aqueductal stenosis occurring in an 11-year-old boy who suffered from mumps meningoencephalitis 9 years previously. The boy was successfully treated by endoscopic third ventriculostomy. CONCLUSIONS: The present case offers further evidence of the purely obstructive nature of the hydrocephalus induced by paramyxovirus meningoencephalitis, even if it did occur several years after the infectious disease. The pathogenesis of mumps-induced hydrocephalus and the rationale of treatment are discussed, and the literature is reviewed.

Efficacy of sequential chemotherapy including methotrexate and doxorubicin in an infant with partially resected choroid plexus carcinoma.

This report refers to a 3-month-old male, with a residual choroid plexus carcinoma following partial resection, who was successfully treated with sequential chemotherapy without any postoperative radiation therapy. Along with carboplatin, we also used doxorubicin and methotrexate, hypothesizing that, given the patient's age, the blood-brain barrier should not hamper drug delivery to the tumor. According to this hypothesis, the treatment achieved complete remission of the disease, which lasts 27 months after the diagnosis. This result deserves further studies to assess the possible curative role of chemotherapy in very young patients suffering from choroid plexus carcinoma.

Cytogenetic evaluation of isochromosome 17q in posterior fossa tumors of children and correlation with clinical outcome in medulloblastoma. Detection of a novel chromosomal abnormality.

BACKGROUND: A number of chromosomal abnormalities have been described in the presence of central nervous system tumors; isochromosome 17q, representing a loss of heterozygosity for the short arm of the chromosome 17, is the one most frequently reported in association with medulloblastoma. The purpose of this study was to evaluate the prognostic correlation of this variable, compared with other variables (surgery extent and radiotherapy), with survival. METHODS AND RESULTS: We looked for the presence of i(17q) in 32 children affected by posterior fossa tumors, including 16 medulloblastomas and 2 teratoid/rhabdoid tumors. For our study we used both karyotypic analysis and the fluorescence in situ hybridization (FISH) procedure, both on fresh and on paraffin-embedded tissues. Cytogenetic analysis allowed us to detect a hitherto unreported abnormality in medulloblastoma: ins(1;10)(q31;q23q26). Moreover, 16 of the 32 patients analyzed by FISH were found to be positive for the presence of i(17q): the 2 with teratoid/rhabdoid tumors, 11 of 16 with medulloblastomas, plus 1 with ependymoblastoma and 2 with anaplastic astrocytomas. As far as the outcome of medulloblastoma patients is concerned, we found that 8 out of the 10 children whose tumor had been totally removed had a favorable outcome regardless of the presence of i(17q): 4 were i(17q) positive and 4 i(17q) negative. CONCLUSIONS: Although it was impossible to draw any definitive conclusion about detection of i(17q) in central nervous system tumors in infancy, particularly in the case of medulloblastoma, we suggest that this chromosomal abnormality is not an independent prognostic factor, but may be a marker for uncontrolled cell proliferation.

The treatment of the positional plagiocephaly with a new thermoplastic orthotic device.

INTRODUCTION: An increasing number of infants presenting with posterior cranial asymmetry are referred to the paediatric neurosurgeon for clinical evaluation. Most of these cranial dysmorphisms cannot be due to lambdoidal sinostosis, since they originate from pre- (intrauterine constraint) or postnatal (prematurity, torticollis, sleeping position) predisposing factors that have deformed the cranial vault. In the literature there is broad consensus about the conservative management of this nonsynostotic plagiocephaly by means of "positional therapy" or "orthoplasty moulding" with cranial helmets or bands. Some reports can be found about the effectiveness of so-called dynamic orthotic cranioplasty (DOC) to improve the cranial asymmetry. TECHNICAL NOTE: In order to simplify the manufacturing procedure and improve the modulation of the corrective forces, we have designed a new orthotic device (thermoplastic orthotic device, TOD) using thermoplastic materials that can be moulded directly on the infant's head. CONCLUSION: With this technique it is no longer necessary to take any cranial impressions and the orthotic device can be easily remodelled, ensuring perfect adaptability of the device to the cranial vault throughout the entire treatment. Moreover, the superior flexibility of this orthosis allows modulation of the corrective forces.