Sapienza Global Bedside Evaluation of Swallowing after Stroke: the GLOBE-3S study.

BACKGROUND AND PURPOSE: Dysphagia occurs in up to 50% of all patients with acute stroke. There is debate regarding which is the most effective screening tool in identifying aspiration in patients with acute stroke. We assessed the accuracy of the Sapienza Global Bedside Evaluation of Swallowing after Stroke (GLOBE-3S), which combines the Toronto Bedside Swallowing Screening Test (TOR-BSST©) with oxygen desaturation and laryngeal elevation measurement during swallowing. METHODS: We prospectively enrolled consecutive patients with stroke within 72 h of symptom onset. All patients with stroke firstly underwent a standard neurological examination, then the GLOBE-3S evaluation and finally the fiberoptic endoscopic evaluation of swallowing (FEES). Two different assessors, a neurologist and a speech pathologist, blind to both the clinical data and each other's evaluation, administered the GLOBE-3S and FEES examination. We assessed the accuracy of the GLOBE-3S in detecting post-stroke swallow impairment with aspiration using the FEES as the standard. RESULTS: We enrolled 50 patients with acute stroke, 28 of whom (56%) had swallowing impairment with aspiration at FEES evaluation. A total of 33 patients (66%) failed the GLOBE-3S evaluation. The GLOBE-3S reached a sensitivity of 100% and a specificity of 77.3% (negative predictive value, 100%; positive likelihood ratio, 4.34). The median time required for the GLOBE-3S to be performed was 297 s. CONCLUSIONS: GLOBE-3S is quick to perform at the bedside and can accurately identify aspiration in patients with acute stroke. By including the measurement of laryngeal elevation and monitoring of oxygen desaturation, it could represent a highly sensitive instrument to avoid the misdiagnosis of silent aspirators.

Treatment patterns from 647 patients with Gaucher disease: An analysis from the Gaucher Outcome Survey.

The Gaucher Outcome Survey (GOS) is an international disease-specific registry established in 2010 for patients with a confirmed diagnosis of Gaucher disease (GD), regardless of GD type or treatment status. For insight into how GD management varies among countries, we analyzed treatment patterns in GOS. As of October 30, 2015, data on GD-specific treatment (enzyme replacement therapy, substrate reduction therapy, or chemical chaperone therapy) received at any time were available for 647 patients. At analysis, velaglucerase alfa (316/573, 55.1%) and imiglucerase (184/573, 32.1%) were the treatments most widely used. Of the 647 treated patients, 446 (68.9%) had been treated for >5years and 368 (56.9%) had received only one GD-specific drug therapy. There were 377 patients who received velaglucerase alfa. Velaglucerase alfa was most widely used at 60U/kg every other week (134/492 dose entries, 27.2%), but there were differences in dosing between the three highest-enrolling countries (defined as >100 GOS patients enrolled in each), with most patients in Israel receiving <20U/kg, most patients in the United Kingdom receiving 20 to <40U/kg, and most in the United States receiving 60U/kg. This analysis provides a foundation upon which to examine real-life outcomes data from different treatment regimens globally.

Neurophysiological correlates of clinical improvement after greater occipital nerve (GON) block in chronic migraine: relevance for chronic migraine pathophysiology.

BACKGROUND: Therapeutic management of Chronic Migraine (CM), often associated with Medication Overuse Headache (MOH), is chiefly empirical, as no biomarker predicting or correlating with clinical efficacy is available to address therapeutic choices. The present study searched for neurophysiological correlates of Greater Occipital Nerve Block (GON-B) effects in CM. METHODS: We recruited 17 CM women, of whom 12 with MOH, and 19 healthy volunteers (HV). Patients had no preventive treatment since at least 3 months. After a 30-day baseline, they received a bilateral betamethasone-lidocaine GON-B of which the therapeutic effect was assessed 1 month later. Habituation of visual evoked potentials (VEP) and intensity dependence of auditory evoked potentials (IDAP) were recorded before and 1 week after the GON-B. RESULTS: At baseline, CM patients had a VEP habituation not different from HV, but a steeper IDAP value than HV (p = 0.01), suggestive of a lower serotonergic tone. GON-B significantly reduced the number of total headache days per month (- 34.9%; p = 0.003). Eight out 17CM patients reversed to episodic migraine and medication overuse resolved in 11 out of 12 patients. One week after the GON-B VEP habituation became lacking respect to baseline (p = 0.01) and to that of HV (p = 0.02) like in episodic migraine, while the IDAP slope significantly flattened (p < 0.0001). GON-B-induced reduction in headache days positively correlated with IDAP slope decrease (rho = 0.51, p = 0.03). CONCLUSIONS: GON-B may be effective in the treatment of CM, with or without MOH. The pre-treatment IDAP increase is compatible with a weak central serotonergic tone, which is strengthened after GON-B, suggesting that serotonergic mechanisms may play a role in CM and its reversion to episodic migraine. Since the degree of post-treatment IDAP decrease is correlated with clinical improvement, IDAP might be potentially useful as an early predictor of GON-B efficacy.

Neuroanatomical, Clinical and Cognitive Correlates of Post-Stroke Dysphagia.

BACKGROUND AND PURPOSE: About half of the dysphagic stroke patients have persistent swallowing dysfunction after 7 days from symptom onset. The aim of the study was to evaluate incidence, prognosis, clinical and neuroradiological correlates of post-stroke dysphagia. METHODS: We prospectively examined consecutive patients with acute ischemic or hemorrhagic stroke. Patients' clinical and neuroradiological data were collected. Swallowing function was assessed by the water swallow test upon admission and after 14 days; patients were then classified as persistent dysphagic, non-persistent dysphagic or non-dysphagic. RESULTS: We recruited 275 patients, 121 of whom were dysphagic upon admission and 254 patients attended follow-up at 14 days; 141 never presented dysphagia, 21 had a non-persistent pattern of dysphagia and 92 had a persistent one. Stroke type, leukoaraiosis degree, previous cognitive impairment and stroke severity upon admission independently predicted the occurrence of dysphagia after stroke and its persistence as well. At receiver operating characteristic (ROC) analysis, the National Institutes of Health Stroke Scale (NIHSS) score of 11.5 was the best predictive value of persistent dysphagia, with a specificity of 90.1% and a sensitivity of 72.4%. CONCLUSION: Stroke severity is an important predictor of a persistent pattern of dysphagia, with a suggested NIHSS cutoff value of ≥12. An independent correlation was observed with leukoaraiosis and with previous cognitive impairment.

Exploring the Therapeutic Potential of Quadripulse rTMS over the Visual Cortex: A Proof-of-Concept Study in Healthy Volunteers and Chronic Migraine Patients with Medication Overuse Headache.

In chronic migraine with medication overuse (CM-MOH), sensitization of visual cortices is reflected by (i) increased amplitude of stimulus-evoked responses and (ii) habituation deficit during repetitive stimulation. Both abnormalities might be mitigated by inhibitory transcranial neurostimulation. Here, we tested an inhibitory quadripulse repetitive transcranial magnetic stimulation (rTMS-QPI) protocol to decrease durably visual cortex excitability in healthy subjects (HS) and explored its therapeutic potential in CM-MOH patients. Pattern-reversal visual evoked potentials (VEP) were used as biomarkers of effect and recorded before (T1), immediately after (T2), and 3 h after stimulation (T3). In HS, rTMS-QPI durably decreased the VEP 1st block amplitude (p < 0.05) and its habituation (p < 0.05). These changes were more pronounced for the P1N2 component that was modified already at T2 up to T3, while for N1P1 they were significant only at T3. An excitatory stimulation protocol (rTMS-QPE) tended to have an opposite effect, restricted to P1N2. In 12 CM-MOH patients, during a four-week treatment (2 sessions/week), rTMS-QPI significantly reduced monthly headache days (p < 0.01). In patients reversing from CM-MOH to episodic migraine (n = 6), VEP habituation significantly improved after treatment (p = 0.005). rTMS-QPI durably decreases visual cortex responsivity in healthy subjects. In a proof-of-concept study of CM-MOH patients, rTMS-QPI also has beneficial clinical and electrophysiological effects, but sham-controlled trials are needed.

Occupational Therapy in Fatigue Management in Multiple Sclerosis: An Umbrella Review.

Background. Fatigue is one of the most invalidant symptoms of Multiple Sclerosis (MS) that negatively affects occupational and work performance and social participation. Occupational therapy (OT) assessment and treatment of impairments related to fatigue can have a significant and positive impact on the quality of life. Methods. An umbrella review has been carried out to provide rehabilitative decision makers in healthcare with insight into the role of OT in fatigue management in Multiple Sclerosis. The question is, what type of treatment provided by occupational therapist is more effective in reducing fatigue in Multiple Sclerosis? A search of literature published until June 2018 was undertaken by three independent reviewers using PubMed, PEDro, and Cochrane Library database including systematic reviews and meta-analyses of the last 10 years. Results. 10 studies were selected (5 systematic reviews, 1 meta-analysis, 3 reviews, and 1 guideline). Conclusions. Fatigue management programs have moderate evidence; other strategies such as OT strategies and telerehabilitation show low evidence.

Biodistribution of indium-111-labeled antibody directed against intercellular adhesion molecule-1.

UNLABELLED: We examined the biodistribution in normal rats of an 111In-labeled mouse monoclonal antibody to rat intercellular adhesion molecule-1 (111In-alCAM-1), as a potential detector of inflammation. METHODS: Indium-111-alCAM-1 or 111In-labeled normal mouse polyclonal immunoglobulin G (111In-nmIgG) was injected into rats. Groups of three to four rats were killed up to 18 hr after injection, and activity was measured in various tissues. Rats were also imaged at 1 and 18 hr after injection. RESULTS: Uptake of 111In-alCAM-1 was greatest in the lung (approximately 10% injected dose [ID]/g at 15 min) and then declined steadily (to approximately 2% ID/g at 18 hr). Lung uptake of 111In-nmIgG was eightfold less than that for 111In-alCAM-1 and did not change throughout the 18 hr. At all time points, blood activity for 111In-alCAM-1 was only 30% to 40% of that for 111In-nmIgG, whereas the percent injected dose per gram was increased more than twofold in the major organs. Compared with 111In-nmIgG, the 111In of alCAM-1 was shifted from the blood and was distributed among the lung kidney, spleen and liver. CONCLUSION: Indium-111-alCAM-1 may be useful as an early inflammation detection agent. Intercellular adhesion molecule-1 upregulation is a very early event in inflammation and rapid removal from the blood of this antibody provides low background in contrast to the usual high background with whole antibodies.

Early detection of bleomycin-induced lung injury in rat using indium-111-labeled antibody directed against intercellular adhesion molecule-1.

UNLABELLED: We have investigated whether an (111)In-labeled mouse monoclonal antibody to rat intercellular adhesion molecule-1 ((111)In*aICAM-1) could detect lung injury early in rats treated with bleomycin. METHODS: Rats received an intravenous injection of either (111)In*aICAM-1 or (111)In-labeled normal mouse IgG ((111)In*nmIgG) and were imaged and killed 24 hr later. Lung injury was induced by an intratracheal injection of bleomycin 4 or 24 hr before the rats were killed. After death, tissue was removed and activity was measured, lungs were cryostat-sectioned to detect the presence of ICAM-1 by immunofluorescence, and the up-regulation of LFA-1alpha was examined on blood polymorphonuclear leukocytes (PMNs) using fluorescence-activated cell-sorter (FACS) analysis. RESULTS: In rats injected with (111)In*aICAM-1, the percent injected dose/organ in lungs both at 4 and 24 hr postbleomycin increased significantly compared to the values in either uninjured rats or rats that received (111)In*nmIgG. At 4 and 24 hr postinjury, the target-to-blood (T/B) ratio was 8/1 and 6/1, respectively. For (111)In*nmIgG, the T/B ratio at 4 hr was 0.5/1 and 0.4/1 at 24 hr. In (111)In*aICAM-1 rats injured at 4 or 24 hr, images could easily be distinguished from uninjured rats. All images of (111)In*nmIgG rats showed only cardiac blood-pool and liver activity with little lung activity. Lung ICAM-1 immunofluorescence intensity increased in the bleomycin-treated samples compared to uninjured lungs. Expression of LFA-1alpha on PMNs increased 19% and 210% at 4 hr and 24 hr postinjury, respectively, compared to control values. CONCLUSION: Biodistribution and imaging data demonstrate that (111)In*aICAM-1 can detect early acute bleomycin-induced lung injury. Immunofluorescence and FACS data suggest that (111)In*ICAM-1 uptake is a specific process. This antibody has potential as an early radionuclide detector of acute inflammations.

Early detection of oleic acid-induced lung injury in rats using (111)In-labeled anti-rat intercellular adhesion molecule-1.

UNLABELLED: Previous study of the bleomycin-induced lung injury model suggested that (111)In-labeled antirat intercellular adhesion molecule-1 (aICAM-1) might be a useful acute respiratory distress syndrome (ARDS) diagnostic agent. We further investigated the ability of (111)In-aICAM-1 to detect inflammation in another ARDS lung injury model. METHODS: (111)In-labeled rat polymorphonuclear leukocytes (PMNs), (111)In-aICAM-1, (111)In-labeled normal mouse IgG (nmIgG), and (111)In-labeled rat serum albumin (RSA) were injected into rats 18-24 h before kill. Biodistributions, scintigraphic images, and lung ICAM-1 upregulation were obtained in uninjured rats and in rats after injury with oleic acid. RESULTS: (111)In-RSA and (111)In-nmIgG localized in inflamed lung at 5 min postinjury (PI). (111)In-PMN uptake increased significantly only at 24 h PI. (111)In-aICAM-1 localization increased significantly (30%-60%) at 1 h PI and remained elevated up to 24 h PI. Lung/blood ratios (L/B) at 1 and 4 h PI were very low (<0.6) for (111)In-nmIgG and (111)In-PMN rats; however, for (111)In-aICAM-1 rats, they were >1 and 25%-60% higher than those for the control samples. A low L/B suggests poor inflammation detection on the images. Images and region-of-interest analysis confirmed that only (111)In-aICAM-1 could distinguish inflamed lungs at 4 h PI. ICAM-1 was upregulated at 4 and 24 h PI. CONCLUSION: In this model, (111)In-aICAM-1 detected lung inflammation very early in the course of the disease. These results support the suggestion that (111)In-aICAM-1 could be a very early, highly specific ARDS diagnostic agent and may be useful to detect a wide range of inflammations.

Construction of a recombinant vaccinia virus expressing the Lassa virus glycoprotein gene and protection of guinea pigs from a lethal Lassa virus infection.

A cloned cDNA (1.65 kb) containing the complete glycoprotein gene of the Josiah strain of Lassa virus was inserted into the thymidine kinase (TK) gene of the New York Board of Health (WYETH) strain of vaccinia virus. The Lassa virus glycoprotein precursor, GPC, and the posttranslational cleavage products, G1 and G2, were shown by Western blot analysis to be properly expressed in cells infected with the recombinant virus. Northern blot hybridization of total cytoplasmic RNA extracted from recombinant virus infected cells demonstrated the presence of RNA transcripts of appropriate size considering the site of transcription initiation from the vaccinia P7.5 promoter, the size of the Lassa glycoprotein gene, and the presumed location of the transcription terminator in the vaccinia thymidine kinase gene. All guinea pigs vaccinated with the recombinant virus survived a lethal challenge infection with Lassa virus, whereas 80% of control animals died. The vaccinated guinea pigs did, however, develop transient, low-grade, fevers and detectable viremias following infection with Lassa virus, indicating that protection was not complete.

Humans with OKT4-epitope deficiency have a single nucleotide base change in the CD4 gene, resulting in substitution of TRP240 for ARG240.

The OKT4 epitope of the CD4 cell-surface protein has been shown to be polymorphic in white, black, and Japanese populations. The variable phenotypic expression is due to an alteration of the OKT4 epitope, since those persons lacking reactivity with OKT4 monoclonal antibody (mAb) are reactive with OKT4A-F mAb as well as other mAb specific for CD4. To determine the nature of this polymorphism at the gene level, we sequenced polymerase chain reaction-amplified genomic DNA containing the CD4-V3 and -V4 exons from American black subjects who are OKT4-normal, OKT4-negative heterozygous, or OKT4-negative homozygous. Comparison of the sequences revealed that the two CD4 exons are identical except for a cytosine-to-thymidine transition occurring at nucleotide position 868. This alters the first codon position of mino acid 240 and results in a tryptophan residue replacing an arginine residue. The change was also found in white and Japanese persons who are OKT4-negative.

Dietary arginine alters time of symptom onset in Huntington's disease transgenic mice.

Recent neuroimaging studies reported complex changes in cerebral blood flow (CBF) in early-staged Huntington's disease (HD) patients. Deckel and co-workers [Deckel and Duffy, Brain Res. (in press); Deckel and Cohen, Prog. Neuro-Psychopharmacol. Biol. Psychiatry 24 (2000) 193; Deckel et al., Neurology 51 (1998) 1576; Deckel et al., J. Nucl. Med. 41 (2000) 773] suggested that these findings might be accounted for, in part, by alterations in cerebral nitric oxide (NO) and its byproduct, peroxynitrite. The current experiment tested this hypothesis by altering NO levels via manipulations of dietary L-arginine (ARG), the dietary precursor of NO, in mice transgenic for HD. Seventy-one mice were assigned at 12 weeks of age to one of three isocaloric diets that varied in their content of ARG. These diets included: (a) 0% ARG, (b) 1.2% ARG (i.e. typical mouse chow), or (c) 5% ARG. The 5% ARG diets in HD mice accelerated the time of onset of body weight loss (P<0.05) and motor impairments (P<0.05), and increased resting CBF in HD relative to control (P<0.05). Conversely, the 0% ARG diet demonstrated no loss of body weight and had no changes in CBF relative to controls. However, the 0% ARG HD group continued to show significant deficits on motor testing (P<0. 05). The 1.2% ARG HD group showed reduced body weight loss, better motor functioning, and fewer changes in CBF compared to the 5% ARG HD group. Immunocytochemistry analysis found greater deposition of nitrotyrosine in the cortex, and vasculature, of HD+ mice, 5% and 1. 2%>0% arginine diets. When collapsed across all conditions, CBF inversely correlated (P<0.05) both with the body weight and motor changes suggesting that changes in CBF are associated with behavioral decline in HD mice. Collectively, these findings indicate that dietary consumption of the NO precursor ARG has a measurable, but complex, effect on symptom progression in HD transgenic mice, and implicates NO in the pathophysiology of HD.

[3H]Rauwolscine: an antagonist radioligand for the cloned human 5-hydroxytryptamine2b (5-HT2B) receptor.

In previous reports, [3H]5-HT has been used to characterize the pharmacology of the rat and human 5-HT2B receptors. 5-HT, the native agonist for the 5-HT2B receptor, has a limitation in its usefulness as a radioligand since it is difficult to study the agonist low-affinity state of a G protein-coupled receptor using an agonist radioligand. When using [3H]5-HT as a radioligand, rauwolscine was determined to have relatively high affinity for the human receptor (Ki human = 14.3+/-1.2 nM, compared to Ki rat = 35.8+/-3.8 nM). Since no known high affinity antagonist was available as a radioligand, these studies were performed to characterize [3H]rauwolscine as a radioligand for the cloned human 5-HT2B receptor expressed in AV12 cells. When [3H]rauwolscine was initially tested for its usefulness as a radioligand, complex competition curves were obtained. After testing several alpha2-adrenergic ligands, it was determined that there was a component of [3H]rauwolscine binding in the AV12 cell that was due to the presence of an endogenous alpha2-adrenergic receptor. The alpha2-adrenergic ligand efaroxan was found to block [3H]rauwolscine binding to the alpha2-adrenergic receptor without significantly affecting binding to the 5-HT2B receptor and was therefore included in all subsequent studies. In saturation studies at 37 degrees C, [3H]rauwolscine labeled a single population of binding sites, Kd = 3.75+/-0.23 nM. In simultaneous experiments using identical tissue samples, [3H]rauwolscine labeled 783+/-10 fmol of 5-HT2B receptors/mg of protein, as compared to 733+/-14 fmol of 5-HT2B receptors/mg of protein for [3H]5-HT binding. At 0 degrees C, where the conditions for [3H]5-HT binding should label mostly the agonist high affinity state of the human 5-HT2B receptor, [3H]rauwolscine (Bmax = 951+/-136 fmol/mg), again labeled significantly more receptors than [3H]5-HT (Bmax = 615+/-34 fmol/mg). The affinity of [3H]rauwolscine for the human 5-HT2B receptor at 0 degrees C did not change, Kd = 4.93+/-1.27 nM, while that for [3H]5-HT increased greatly (Kd at 37 degrees C = 7.76+/-1.06 nM; Kd at 0 degrees C = 0.0735+/-0.0081 nM). When using [3H]rauwolscine as the radioligand, competition curves for antagonist structures modeled to a single binding site, while agonist competition typically resulted in curves that best fit a two site binding model. In addition, many of the compounds with antagonist structures displayed higher affinity for the 5-HT2B receptor when [3H]rauwolscine was the radioligand. Typically, approximately 85% of [3H]rauwolscine binding was specific binding. These studies display the usefulness of [3H]rauwolscine as an antagonist radioligand for the cloned human 5-HT2B receptor. This should provide a good tool for the study of both the agonist high- and low-affinity states of the human cloned 5-HT2B receptor.

Punctiform and polychromatic pre-Descemet's dominant corneal dystrophy.

A new type of pre-Descemet's corneal dystrophy is described. The opacities are punctiform, polychromatic, of uniform size, and evenly distributed over the whole cornea. The diagnosis is made only by slit lamp because there is no visual impairment. The disease is hereditary and follows the autosomal mode of inheritance with a high percentage of penetrance, expressivity, and specificity in 4 successive generations, in which 8 affected members were observed among a total of 46.

Venezuelan equine encephalomyelitis vaccine (strain TC-83): a field study.

In 1971, more than 370 horses in south Texas were studied with respect to their clinical, virologic, and neutralizing antibody responses to vaccination with Venezuelan equine encephalomyelitis (VEE) strain TC-83. This study confirms reported findings that the vaccine used in the 1971 epizootic in the lower Rio Grande Valley of Texas was safe and efficacious. Vaccinal virus viremia titers were generally below the postulated infection threshold of epizootic vectors. In general, reactions to the vaccine were minimal and transient, with no observed abortions or deaths attributable to use of the vaccine. Eleven months after vaccination, VEE antibody titers were demonstrable in most horses that had VEE antibodies within 30 days after vaccination. Presence of western equine encephalomyelitis antibody titers of greater than or equal to 1:50 at time of VEE vaccination appears to modify or to interfere with VEE antibody production.

[Mitral valve substitution, using the Lillehei-Kaster prosthesis]. / La sostituzione valvolare mitralica con la protesi di Lillehei-Kaster.

Personal experience acquired in the course of 177 mitral valve replacements with a Lillehei-Kaster prosthesis up to June 1977 is discussed. Intraoperative mortality was 8.5%. Postoperative mortality (as at 31-12-1976) was 5.3%. The clinical, radiological, and ergometric findings were fully satisfactory. Haemodynamic examination at rest and during effort revealed improved pressure and heart capacity values. The mean transprosthetic gradient at rest was 5.61 and rose to 13.53 (after uncalibrated effort). Thromboembolism was noted in 5 patients (3.1%), as in the literature. The haemodynamic features and low thrombogenicity of the Lillehei-Kaster prosthesis would thus appear to make it a sound replacement for the mitral valve.

[Major complications of median sternotomy]. / Le complicanze maggiori della sternotomia mediana.

After examining the modalities of sternal perfusion and the techniques of median sternotomy, with special regard to closure techniques, personal experience of 1000 sternotomies is reviewed. Complications may be major or minor, incidence was 1,8% and total mortality two cases. After reviewing the various causes of sternal dehiscence, reported and personal experience of the various techniques for preventing and treating the complication is discussed.

[Pancreatic cysts]. / Le cisti pancreatiche

True and pseudo-cysts of the pancreas are described and their aetiology, pathology, laboratory tests, radiological examination, differential diagnosis, symptomatology and surgical management are illustrated. A series of 22 cases of pancreatic cyst is presented. Surgical management consisted of 14 cystogastrostomies, 3 cystoduodenostomies, 2 resections of the tail of the pancreas, 1 internal drainage between the fistular segment of the gland and the gastric cavity, and 2 external drainages with a Pezzer tube. It is felt that internal drainage is the operation of choice. Of the surgical techniques available, a preference is expressed for cystogastrostomy and cystoduodenostomy.

Successful treatment of metastatic retinoblastoma with high-dose chemotherapy and autologous stem cell rescue in South America.

High-dose chemotherapy (HDC) followed by autologous stem cell rescue (ASCR) is the only curative treatment for metastatic retinoblastoma, but its feasibility in developing countries is unknown. We report 11 consecutive children (six unilateral) treated in three South-American middle-income countries with HDC-ASCR. One patient had metastatic retinoblastoma at diagnosis and the remaining ones had a metastatic relapse. Metastatic sites included BM=6, bone=4, orbit=5 and central nervous system (CNS)=4. All patients received induction with conventional chemotherapy achieving CR at a median of 5.7 months from the diagnosis of metastasis. Conditioning regimens included carboplatin and etoposide with thiotepa in six or with CY in four or melphalan in one patient. All patients engrafted after G-CSF-mobilized peripheral blood ASCR and no toxic deaths occurred. Two children received post-ASCR CNS radiotherapy. Seven children have disease-free survival (median follow-up 39 months). CNS relapse, isolated (n=3) or with systemic relapse (n=1), occurring at a median of 7 months after ASCT was the most common event. In the same period, five children with metastatic retinoblastoma did not qualify for HDC-ASCR and died. We conclude that HDC-ASCR is a feasible and effective treatment for children with metastatic retinoblastoma in middle-income countries.