ERIGO: a possible strategy to treat orthostatic hypotension in progressive supranuclear palsy? A feasibility study.

Progressive supranuclear palsy (PSP) is a neurodegenerative disease of the central nervous system, presenting with different clinical phenotypes, all involving the extrapyramidal system. Orthostatic hypotension (OH) is a common symptom of cardiovascular autonomic dysfunction. OH is defined as a fall in systolic blood pressure of at least 20 mmHg and/or a fall in diastolic blood pressure of at least 10 mmHg on standing or head-up tilt. In this pilot study, we tested the feasibility and efficacy of the ERIGO® device in managing OH non-responsive to conventional treatments in a sample of patients with PSP. OH was chosen as the primary outcome, as the symptom is a serious complication in neurodegenerative disorders, challenging the rehabilitation treatment. Six patients received intensive training using ERIGO®, a robot- assisted tilt table with an integrated leg movement system that allows progressive verticalization of the patient, and application of functional electrical stimulation. In all the participants, OH improved after the training with the device, suggesting that robotic verticalization may be a feasible and effective tool in improving blood pressure stability in patients with PSP. Further studies in larger samples, also including patients with other neurodegenerative disorders associated with OH, are needed to confirm these promising results.

Cytomegalovirus anterior uveitis: long-term follow-up of immunocompetent patients.

BACKGROUND: We aimed to report on the clinical findings and long-term prognosis of patients with cytomegalovirus (CMV) anterior uveitis. METHODS: This was a retrospective observational study on 15 immunocompetent patients with CMV anterior uveitis and a follow-up longer than 24 months (mean: 62.1 ± 28.5 months). RESULTS: Uveitis was unilateral and hypertensive in all cases, with acute relapsing having the characteristics of Posner-Schlossman syndrome in nine (60 %) and chronic in nine patients (40 %), three of whom were clinically classified as Fuchs' heterocromic iridocyclitis (20 %). All patients received topical antiviral and corticosteroid therapy, with six patients also receiving systemic therapy with valganciclovir or acyclovir. The mean number of uveitis relapses significantly decreased, before and after anti-CMV therapy, from 0.23 ± 0.17 to 0.03 ± 0.03 (p < 0.001), without significant differences among patients treated with topical therapy alone or combined topical and systemic therapy. Cataracts developed in nine out of 13 patients (69.2 %). A chronic raise in intraocular pressure (IOP) was found in 13 patients (86.6 %), with nine requiring surgery (60 %). At the end of the follow-up, all patients had a quiescent uveitis, with ten of them requiring topical low dose steroid therapy (66.6 %) and combined with systemic acyclovir in four cases. Eight patients (53.3 %) were on antiglaucomatous therapy. The last mean IOP value was 14.9 ± 3.6 mmHg (range 8-21 mmHg), and visual acuity was 0.89 ± 0.21. CONCLUSIONS: CMV-associated anterior uveitis has a fairly good long-term visual prognosis. Antiviral therapy can reduce the frequency of relapses, but cataracts and a chronic raise in IOP are frequent complications often requiring a surgical approach.

Knee joint synovitis in Behçet's disease: a sonographic study.

OBJECTIVE: The aim of this study was to investigate, using ultrasound (US), knee involvement in patients with Behçet's disease (BD). METHODS: Knee US was performed in 30 unselected Italian BD patients. Signs of arthritis (joint effusion, synovial proliferation) and presence of bone erosions and Baker's cysts were recorded. Power Doppler evaluation was performed. A semi-quantitative score was used for each structure examined, whereby 0 was to indicate the absence of any change and score from 1 to 3 the presence of mild to severe changes. A sum of the single scores was obtained. Disease activity was evaluated to identify the correlation with the US modifications. RESULTS: Twenty (66.6%) patients had symptomatic articular involvement and US showed knee involvement in 18 of them (60%). Synovial proliferation was detected in 14 (46%, positive power Doppler in 4), joint effusion in 14 (46%), bone surface erosions in 3 (10%). Four patients, asymptomatic for joint involvement, showed US alterations. Eleven patients showed a total score between 1 and 3, while the other 7 had a score between 4 and 6. Subjects with a higher US score presented an increased prevalence of acneiform skin lesions with respect to the group with US score 1-3. Statistical analysis showed a positive correlation between disease activity and US score in group 2 (p=0.04). CONCLUSION: This study confirms that peripheral joint involvement represents an important clinical aspect in italian BD patients and US evaluation is useful for the detection of this aspect.

Vogt-Koyanagi-Harada disease after head trauma.

PURPOSE: To report two cases of Vogt-Koyanagi-Harada disease after closed head trauma. METHODS: Case report. RESULTS: Two patients, one male and one female, developed headache, dysacusis, vertigo, tinnitus, and hair hypersensitivity shortly after a closed head trauma and, 10 and 18 days later, a bilateral uveitis with papillitis and exudative retinal detachment in one and a bilateral mild uveitis with macular exudative detachment in the other. The ocular lesions resolved with intravenous high-dose steroid therapy, but recurred after reduction of the dosages, requiring further steroid therapy. The course of the disease in both patients, with the appearance of fundus depigmentation and pigment clumping, and the occurrence of a concomitant ocular and auditory relapse in one, were typical of Vogt-Koyanagi-Harada disease. CONCLUSIONS: Vogt-Koyanagi-Harada disease may appear after a closed head trauma suggesting that even an indirect trauma in melanocyte-containing tissue may induce an inflammatory response within the eye.

Changing patterns of ocular manifestations in HIV seropositive patients treated with HAART.

PURPOSE: To report the changing patterns of ocular manifestations in human immunodeficiency virus (HIV) seropositive patients treated with highly active antiretroviral therapy (HAART). METHODS: The clinical charts of HIV seropositive patients, 735 examined from 1997 to 2003 and treated with HAART for at least 2 months (Group 1), and 838 untreated examined from 1988 to 1995 (Group 2), were reviewed to assess the frequency of ocular manifestations. RESULTS: HIV-related retinal microangiopathy and opportunistic retinal infections (cytomegalovirus retinitis and toxoplasmic retinochoroiditis) were significantly higher in Group 2 than 1 (p<0.0001), while in patients treated with HAART a statistically significant increase in the frequency of chalazion (p<0.0001), diabetic and hypertensive retinopathy (p<0.0001), lipid arc of the cornea (p<0.0001), cataract and glaucoma (p<0.0001), and uveitis (p=0.026) was observed. CONCLUSIONS: HAART therapy has induced a dramatic decrease in the incidence of HIV-related microangiopathy and opportunistic retinal infection and the occurrence of new lesions related both to the metabolic alterations induced by HAART and to immune reconstitution, such as uveitis.

Polymorphism of the Duffy erythrocyte chemokine receptor in Italian patients with Behçet's disease.

This study examined the hypothesis that the polymorphism of Duffy antigen receptor for chemokines (DARC) predisposes to and/or influences the clinical manifestations of Behçet's disease. The serum levels of IL-8 and monocyte chemotactic peptide (MCP)-1, two DARC-binding chemokines, were investigated and related to this polymorphism. Twenty-eight patients with Behçet's disease and 30 healthy blood donors were included in the study. No null phenotypes were found among the patients studied, and the frequencies of the other phenotypes (Fy((a+b-)), Fy((a+b+)), and Fy((a-b+))) did not significantly differ from those found in the blood donor group or reported in the general Caucasian population. No difference was found between the single phenotypes in terms of IL-8 and MCP-1 serum levels, and no relevant association between the clinical characteristics, Behçet's disease-associated human leukocyte antigen (HLA)-B51, and single phenotypes was observed. This investigation indicates that DARC is not a genetic trait significantly associated with or predisposing to Behçet's disease, at least in Caucasian Italians. However, the role of this polymorphism in the development and in the clinical course of the disease awaits further investigation.

Indocyanine green angiographic findings in Behçet disease.

BACKGROUND: The authors studied indocyanine green (ICG) angiographic features in proven cases of ocular Behçet disease. METHODS: Twenty-six patients (18 male, 8 female; mean age 39.9 +/- 8.9 years) with Behçet disease underwent simultaneous ICG and fluorescein angiography (FA) according to a uveitis angiographic standard protocol. Patients were divided into three groups based on their ocular disease duration: Group A (9 patients), less than 3-year duration; Group B (8 patients), 4- to 10-year duration; Group C (9 patients), more than 10-year duration. The relation between ICG angiographic findings and ocular disease duration and FA signs was delimited. RESULTS: Three findings were disclosed by ICG angiography: 1) poorly defined areas of intermediate and late hyperfluorescence (50% of eyes); 2) well-defined hypofluorescent areas becoming isofluorescent in the late phase (26.92% of eyes); and 3) large, poorly defined hypofluorescent areas visible up to the late phase (30.77% of eyes). The presence of ICG hypofluorescent areas up to the late phase was related to disease duration (P = 0.01), whereas ICG hypofluorescent areas becoming isofluorescent in the late phase were predominant in patients in early stages of ocular disease (P = 0.02). The presence or absence of FA signs did not indicate any significant correlation with the presence or absence of signs revealed by ICG angiography. CONCLUSION: Indocyanine green angiography enabled the identification of different choroidal abnormalities related to the ocular disease duration. The presence of some ICG findings undetectable with FA suggests that ICG and FA are complementary means to diagnose and monitor ocular vascular involvement in patients with Behçet disease.

Treatment of severe ocular hypotony in AIDS patients with cytomegalovirus retinitis and cidofovir-associated uveitis.

OBJECTIVE: To describe the medical treatment of severe ocular hypotony in HIV-seropositive patients with cytomegalovirus retinitis and cidofovir-associated uveitis. PATIENTS AND METHODS: Two HIV-seropositive patients with cytomegalovirus retinitis and cidofovir-associated uveitis complicated by severe ocular hypotony were unresponsive to conventional therapy after treatment with cidofovir was stopped. They were subsequently treated successfully with ibopamine 2% eyedrops and dexamethasone 0.1% eyedrops. RESULTS: In both cases, an increase in intraocular pressure to normal values was observed on average 18.5 days after starting treatment. Intraocular pressure remained stable while on therapy for a mean follow-up of 9.5 months. During the follow-up period, any attempt to stop treatment was followed by an intraocular pressure decrease; conversely, restoration of therapy increased intraocular pressure to normal values. No reactivation of cidofovir-associated uveitis or cytomegalovirus retinitis was observed during the follow-up period. CONCLUSIONS: Ibopamine 2% eyedrops in combination with dexamethasone 0.1% eyedrops is a satisfactory therapy for severe ocular hypotony in patients with cytomegalovirus retinitis and cidofovir-associated uveitis.

Localization of the pathogenic gene of Behçet's disease by microsatellite analysis of three different populations.

PURPOSE: Behçet's disease (BD) is known to be associated with HLA-B51 in many ethnic groups. However, the pathogenic gene responsible for BD is as yet unknown. To localize the critical region of the pathogenic gene, microsatellite markers distributed around the HLA-B gene were investigated. The BD patients studied were of three ethnic origins: Japanese, Greek, or Italian. METHODS: The total group consisted of 172 BD patients, of whom were 95 Japanese, 55 Greek, and 22 Italian. Eight polymorphic microsatellite markers distributed within 1100 kb of the HLA-B gene were analyzed using PCR and subsequent automated fragment detection by fluorescent-based technology. RESULTS: Among the eight markers, allele 348 of the MIB microsatellite was remarkably common in all three BD populations (Japanese, PC: = 0.000014; Greek, PC: = 0. 00047; Italian, PC: = 0.11). However, HLA-B51 was found to be the marker most strongly associated with BD in each population (Japanese, PC: = 0.000000000017; Greek, PC: = 0.00000032; Italian, PC: = 0. 0074). In genotypic differentiation between the patients and controls, only HLA-B51 was found to be significantly associated with BD in all three populations. Stratification analysis suggested that significant associations of BD with MICA and other microsatellites resulted from a linkage disequilibrium with HLA-B51. CONCLUSIONS: These results suggest that the pathogenic gene of BD is HLA-B51 itself and not other genes located in the vicinity of HLA-B.

Long-term follow-up of anterior uveitis after cataract extraction and intraocular lens implantation.

PURPOSE: To assess whether cataract surgery and intraocular lens (IOL) implantation in patients with anterior uveitis interfere with the natural course of the ocular disease. SETTING: Tertiary care center at the University of Rome "La Sapienza", Rome, Italy. METHODS: Cataract extraction and IOL implantation were performed in 24 patients with uveitis-related cataract: 12 with Fuchs' heterochromic iridocyclitis (Group 1) and 12 with other types of anterior uveitis (Group 2). The mean follow-up in the 2 groups was 33.6 months and 24.8 months, respectively. The number and severity (inflammatory score) of uveitis relapses in all patients over the same period were recorded. RESULTS: After surgery, the mean number and severity of uveitis relapses decreased: Group 1, from 1.83 +/- 1.90 (SD) to 1.00 +/- 1.21 and from 1.08 +/- 0.90 to 0.92 +/- 0.67, respectively; Group 2, from 2.74 +/- 3.44 to 1.25 +/- 1.71 and from 1.83 +/- 1.10 to 1.25 +/- 0.75, respectively (P = .046). There were no statistically significant between-group differences. In Group 2, a trend toward worse visual rehabilitation was seen; this was significantly different from the result in Group 1 (P = .018) because of preoperative optic nerve damage, macula disease, or both. CONCLUSION: Cataract surgery and IOL implantation did not negatively influence the natural course of uveitis in patients with Fuchs' heterochromic iridocyclitis. Correct surgical timing, selection of cases, and adequate anti-inflammatory therapy may promote similar results in patients with other types of anterior uveitis.

Herpes simplex virus vaccine in recurrent herpetic ocular infection.

PURPOSE: To evaluate the efficacy of an antiherpetic vaccine in recurrent herpetic ocular infections. METHODS: Twenty patients with herpes simplex virus 1-related recurrent keratitis/keratouveitis were prospectively enrolled and randomly assigned to receive either a specific vaccination with heat shock-inactivated herpes simplex virus type 1 (10 patients) or to be observed as controls (10 patients). The number, duration, and anatomic localization of relapses were recorded in all the patients for 12 months before inclusion in the study and for a similar period after the assignment of each subject to vaccine or control group. RESULTS: In the vaccine group, we observed a reduction both in the number (p = 0.016) and average duration (p = 0.050) of recurrences, whereas in the control group, no significant change was found comparing a 12-month period before and after inclusion in the study. The comparison between the two groups highlighted a significant reduction in the number (p = 0.013) and average duration (p = 0.051) of relapses in treated subjects, who did not show any significant vaccine-induced side effects. CONCLUSION: The use of a vaccination with heat shock-inactivated herpes simplex virus 1 seems to be able to reduce the number and duration of relapses in herpes simplex virus 1-related keratitis/keratouveitis.

Cardiac involvement in Behçet's disease.

To assess the prevalence and the extent of cardiac involvement in patients with Behçet's disease and to investigate the possible causes that may predispose to this involvement, 30 patients affected by Behçet's disease and 30 normal control subjects were submitted to M-mode, two-dimensional, and Doppler echocardiographic evaluation. Moreover, antinuclear and anticardiolipin autoantibodies were determined in the sera of both patients and control subjects. Finally, HLA-B51 positivity was assessed in the patients and in a historical control group. Mitral valve prolapse was observed in 50% and proximal aorta dilatation in 30% of the patients. There was a significant difference in the rate of these abnormalities in comparison with the control group. Left ventricular function parameters were similar between the two groups. The positivity rate of antinuclear and anticardiolipin autoantibodies was very low (7%), without differences between the groups. HLA-B51 was detected in 82.7% of the patients versus 21.7% in the control group (p < 0.00001). In conclusion, this study demonstrates a high rate of cardiac abnormalities in patients with Behçet's disease.

[Magnetic resonance of the encephalon in 17 patients with ocular Behçet's disease]. / Risonanza magnetica dell'encefalo in 17 pazienti affetti da malattia di Behçet oculare.

Behçet's disease is a chronic relapsing disorder of unknown etiology characterized by oral aphthous ulcerations, uveitis, genital ulcerations and bone lesions. A variety of other signs including polyarthritis, vascular conditions (blood vessel occlusions and aneurysms), epididymitis, gastrointestinal, pulmonary and heart lesions may also occur. Central nervous system (CNS) involvement is reported in 10-49% of cases and it is the first symptom of the disease in 5% of subjects. The neuro-Behçet's syndrome may appear as a brainstem syndrome, meningoencephalitis and an organic confusional syndrome or dementia. Cranial hypertension, mostly related to cerebral venous thrombosis, is also present in neuro-Behçet's disease and its incidence is reported in up to 10% of Behçet's patients. MRI is reportedly the most sensitive neuroradiologic approach to detect the focal lesions related to neuro-Behçet's disease and several single cases or series of Behçet's patients with neurologic signs have been examined with MRI. We used MRI to investigate CNS involvement in Behçet's disease patients with and without previous neurologic signs. MRI was carried out on 17 patients with ocular Behçet's disease without neurologic symptoms to assess the possible subclinical involvement of the CNS. Cerebrospinal fluid spaces were enlarged in 8 patients and 5 patients exhibited cortical atrophy. PD and T2-weighted hypersignal foci were demonstrated in parietal, frontal, subcortical and periventricular white matter in 6 subjects. Neuroradiologic abnormalities were found only in the patients with complete disease and with the disease diagnosed more than 10 years earlier. Even though the pathogenesis of these neuroradiologic abnormalities and their correlation with Behçet's disease remain to be clarified, our study suggests the possibility of subclinical CNS involvement in these patients, which may affect the therapeutic approach and their prognosis.

Interferon alpha for ocular Behçet's disease.

PURPOSE: To investigate the therapeutic role of interferon alpha in ocular Behçet's disease. METHODS: Three patients with B- or C-hepatitis and ocular sight-threatening Behçet's disease unresponsive to steroids were treated subcutaneously with interferon alpha 3 x 10(6)/unit three times per week for a mean period of 22 months (range: 12-31 months). The course of ocular and systemic lesions was recorded and compared with a similar pre-treatment period. RESULTS: At least a 50% reduction in the number of ocular relapses was observed in all the patients (mean relapse/month: 0.41 versus 0.16 in the pre- and in-treatment period, respectively) while during therapy also each relapse lasted less in all subjects. A reduction of steroid dependence was observed in all patients, while no significant side-effects were related to interferon alpha administration. Two patients who tried to stop interferon alpha therapy showed after a mean period of 12.5 days a recurrence of diffuse uveitis and, one of them experienced oral and genital aphthae as well. CONCLUSION: In patients with Behçet's disease interferon alpha seems to be a useful alternative therapy for sight-threatening ocular involvement.

Vogt-Koyanagi-Harada disease and HLA type in Italian patients.

PURPOSE: To study the frequencies of human leukocyte antigen (HLA) specificities in Italian patients with Vogt-Koyanagi-Harada disease and to correlate the presence of each specificity to the clinical features. METHODS: Human leukocyte antigen specificities were determined by standard microlymphocytotoxicity assay in 16 patients with Vogt-Koyanagi-Harada disease and compared with HLA specificities of 116 healthy controls. RESULTS: HLA-DR4 was statistically related to Vogt-Koyanagi-Harada disease (P = .0063), whereas only a trend toward a significant association between the disease and HLA-B41 was found (P = .06). HLA-DQ1 was detected in a disproportionate number of controls (68.9%) compared with patients (37.5%). CONCLUSIONS: HLA-DR4 was significantly related to Vogt-Koyanagi-Harada disease in Caucasian European patients, specifically in Italian patients, as it was described in other racial groups. No clear relation was found between the ophthalmologic and systemic manifestations of Vogt-Koyanagi-Harada disease and the presence of HLA specificities.

Pre-symptomatic neurological involvement in Behcet's disease: the diagnostic role of magnetic transcranial stimulation.

Twenty Behcet's disease (BD) patients with or without neurologic signs and symptoms were studied by means of magnetic transcranial stimulation. The most frequent abnormalities were an increase of motor evoked potential latency and a delay of central motor conduction time (CMCT). In 5 out of 9 BD patients with pyramidal signs central motor conduction changes were present. Furthermore, 2 out of 7 patients without neurologic signs and symptoms showed an increased threshold and a prolonged CMCT. The data obtained suggest that this technique is useful not only to confirm the neurologic impairment but also to reveal subclinical or pre-symptomatic central motor involvement in BD subjects.