Joan Berenguer

Prevalence and clinical importance of sleep apnea in the first night after cerebral infarction

ObjectiveTo determine the prevalence of sleep apnea (SA) during the first night after hemispheric ischemic stroke and its influence on clinical presentation, course, and functional outcome at 6 months. MethodsThe first night after cerebral infarction onset, 50 patients underwent polysomnography (PSG) followed by oximetry during the next 24 hours. Neurologic severity and early worsening were assessed by the Scandinavian Stroke Scale and outcome by the Barthel Index. Patients were evaluated on admission, on the third day, at discharge, and at 1, 3, and 6 months. ResultsThere were 30 males and 20 females with a mean age of 66.8 ± 9.5 years. Latency between stroke onset and PSG was 11.6 ± 5.3 hours. Thirty-one (62%) subjects had SA (apnea–hypopnea index [AHI] ≥ 10). Of these, 23 (46%) had an AHI ≥20 and 21 (42%) an AHI ≥25. Sleep-related stroke onset occurred in 24 (48%) patients and was predicted only by an AHI ≥25 on logistic regression analysis. SA was related to early neurologic worsening and oxyhemoglobin desaturations but not to sleep history before stroke onset, infarct topography and size, neurologic severity, or functional outcome. Early neurologic worsening was found in 15 (30%) patients, and logistic regression analysis identified SA and serum glucose as its independent predictors. ConclusionsSA is frequent during the first night after cerebral infarction (62%) and is associated with early neurologic worsening but not with functional outcome at 6 months. Cerebral infarction onset during sleep is associated with the presence of moderate to severe SA (AHI ≥ 25).

Trans-Synaptic Axonal Degeneration in the Visual Pathway in Multiple Sclerosis

To evaluate the association between the damage to the anterior and posterior visual pathway as evidence of the presence of retrograde and anterograde trans‐synaptic degeneration in multiple sclerosis (MS).

A short course of oral prednisone followed by intranasal budesonide is an effective treatment of severe nasal polyps.

Background: Nasal polyposis is an inflammatory disease of unknown etiology. This study aimed to evaluate the effect of a short course of oral prednisone followed by intranasal budesonide on nasal symptoms, polyp size, nasal flow, and computed tomography scan.

Clinical and MRI outcome after autologous hematopoietic stem cell transplantation in MS

The authors report the outcome of 14 patients with severe multiple sclerosis treated with autologous hematopoietic stem cell transplantation (AHSCT) after a median follow-up period of 3 years. The 3-year actuarial probability of progression-free survival was 85.7% and that of disease activity-free survival was 46.4%. On MRI, no T1-enhanced lesions were detected after AHSCT. The mean change in T2 lesion volume from baseline to the third year was −20.2% and that of the corpus callosum area was −12.7%; 50% of this reduction was seen during the first year.

Assessment of α-synuclein in submandibular glands of patients with idiopathic rapid-eye-movement sleep behaviour disorder: a case-control study

BACKGROUND The histological feature of Parkinsons disease is the presence of intraneuronal aggregates of phosphorylated α-synuclein (αSyn). In patients with Parkinsons disease, deposits of αSyn are found in the autonomic nerve fibres of the submandibular gland. Since patients with idiopathic rapid-eye-movement sleep behaviour disorder (IRBD) can develop Parkinsons disease and other synucleinopathies, we investigated whether αSyn deposits could also be detected in their submandibular gland nerve fibres. METHODS We did a case-control study at the Hospital Clinic de Barcelona (Barcelona, Spain) in patients with polysomnographic-confirmed IRBD, patients with clinically diagnosed Parkinsons disease, and controls matched by age with the IRBD group. The controls were either healthy, had had elective neck surgery in the clinic, or were patients who had died in the clinic and had an autopsy. We did a transcutaneous core needle biopsy of the submandibular gland with ultrasound guidance in patients with IRBD or Parkinsons disease, and healthy controls, and without ultrasound guidance in the other controls. We assessed the presence of αSyn with immunohistochemistry using 129-phosphorylated antiserine monoclonal antibody, and analysed quantitative variables with Kruskall-Wallis tests and qualitative variables with Fishers exact tests. FINDINGS We did our study between July 16, 2014, and May 16, 2015, and recruited 21 patients with IRBD, 24 patients with Parkinsons disease, and 26 controls (seven healthy, 11 patients undergoing neck surgery, and eight autopsies). We obtained submandibular biopsy material containing glandular parenchyma in nine (43%) of 21 patients with IRBD, 12 (50%) of 24 patients with Parkinsons disease, and all (100%) of the 26 controls. αSyn aggregates were detected in nerve fibres of the glandular parenchyma in eight (89%) of nine patients with IRBD and eight (67%) of 12 with Parkinsons disease, but none of the controls. Of the individuals whose biopsy samples did not contain glandular parenchyma, deposits of αSyn were found in extraglandular tissues in an additional three (25%) of 12 patients with IRBD and five (42%) of 12 patients with Parkinsons disease. None of the controls showed αSyn immunoreactivity in extraglandular tissues. Of the 52 participants who had ultrasonography-guided biopsy, 11 (21%) reported mild-to-moderate local pain, and nine (17%) developed a subcutaneous haematoma; however, these adverse events were transient and did not need treatment. INTERPRETATION Our findings suggest that, in patients with IRBD, submandibular gland biopsy is a safe procedure for the detection of αSyn aggregates. αSyn detection could be useful for histological confirmation in individuals clinically diagnosed with Parkinsons disease. FUNDING Centre for Networked Biomedical Research in Neurodegenerative Disorders (CIBERNED), Barcelona, Spain.

Randomized placebo-controlled phase II trial of autologous mesenchymal stem cells in multiple sclerosis.

Objective Uncontrolled studies of mesenchymal stem cells (MSCs) in multiple sclerosis suggested some beneficial effect. In this randomized, double-blind, placebo-controlled, crossover phase II study we investigated their safety and efficacy in relapsing-remitting multiple sclerosis patients. Efficacy was evaluated in terms of cumulative number of gadolinium-enhancing lesions (GEL) on magnetic resonance imaging (MRI) at 6 months and at the end of the study. Methods Patients unresponsive to conventional therapy, defined by at least 1 relapse and/or GEL on MRI scan in past 12 months, disease duration 2 to 10 years and Expanded Disability Status Scale (EDSS) 3.0–6.5 were randomized to receive IV 1–2×106 bone-marrow-derived-MSCs/Kg or placebo. After 6 months, the treatment was reversed and patients were followed-up for another 6 months. Secondary endpoints were clinical outcomes (relapses and disability by EDSS and MS Functional Composite), and several brain MRI and optical coherence tomography measures. Immunological tests were explored to assess the immunomodulatory effects. Results At baseline 9 patients were randomized to receive MSCs (n = 5) or placebo (n = 4). One patient on placebo withdrew after having 3 relapses in the first 5 months. We did not identify any serious adverse events. At 6 months, patients treated with MSCs had a trend to lower mean cumulative number of GEL (3.1, 95% CI = 1.1–8.8 vs 12.3, 95% CI = 4.4–34.5, p = 0.064), and at the end of study to reduced mean GEL (−2.8±5.9 vs 3±5.4, p = 0.075). No significant treatment differences were detected in the secondary endpoints. We observed a non-significant decrease of the frequency of Th1 (CD4+ IFN-γ+) cells in blood of MSCs treated patients. Conclusion Bone-marrow-MSCs are safe and may reduce inflammatory MRI parameters supporting their immunomodulatory properties. ClinicalTrials.gov NCT01228266

Central nervous system toxoplasmosis in AIDS patients: efficacy of an intermittent maintenance therapy.

Fifty-five episodes of central nervous system (CNS) toxoplasmosis developing in 43 of the 329 AIDS cases seen at our institution were diagnosed during a 34-month period and were prospectively studied. Acute episodes were treated with a pyrimethamine/sulfadiazine (P/S) combination for a mean of 21 days. Because of a previously known major allergy to sulfonamides, three episodes were treated with clindamycin instead of sulphadiazine. In those patients who accepted maintenance therapy, a combination of P/S or pyrimethamine and clindamycin (P/C) was administered 2 days per week. Thirty-six patients (83.7%) survived the first episode. Four of these 36 were lost to further study. Six of the 12 (50%) who decided not to undergo maintenance therapy relapsed (mean follow-up: 12 months). Fourteen patients were given P/S and none relapsed while they were on maintenance therapy (mean follow-up: 10.3 months). Six patients received an intermittent maintenance treatment with P/C and one relapsed 2 months after starting the maintenance therapy (mean follow-up: 13.7 months). We conclude that an intermittent (2 days per week) maintenance treatment for CNS toxoplasmosis with P/S was effective in preventing relapses, although prospective randomized studies remain to be done.

Assessing the Long-Term Viability of Facial Fat Grafts: An Objective Measure Using Computed Tomography

BACKGROUND Autologous fat transplantation for soft tissue augmentation is a commonly used technique without a universally accepted approach. The literature includes a variety of reports describing varying degrees of success or failure. OBJECTIVE To evaluate the behavior of facial fat grafts in humans with the use of an objective measuring tool. METHODS A prospective randomized study, comparing patients pre- and postoperatively, was designed to evaluate the long-term viability of fat grafting. Participants were 18 men and 8 women between 34 and 59 years of age (mean, 45.07 yrs; standard deviation, 6.54 yrs). A total of 52 hemifaces in 26 patients diagnosed with HIV and demonstrating facial lipoatrophy were treated with fat transplantation using Colemans technique. HIV-positive patients were chosen as study participants because their nearly total lack of subcutaneous fat diminishes the bias in the evaluation of fat volume. Fat graft viability was evaluated by measuring the volume of adipose tissue evolution via computed tomography scan before fat grafting, at the second month after fat grafting, and 1 year after fat grafting. Descriptive statistical analysis was performed. RESULTS The mean volume on the right and left cheeks before fat grafting was 1.57 cc. The mean volume 2 months after the procedure was 2.93 cc with a statistically significant mean increase of 1.36 cc (P < .001) between baseline and the second month after the procedure. The mean volume after 12 months was 3.29 cc (P < .001), with a mean increase compared with the baseline of 1.72 cc, and of 0.36 cc between months 2 and 12. The statistically significant posttreatment improvement (P < .001) was maintained until month 12 of the follow-up period. CONCLUSIONS Using objective measurement, this study demonstrates that with one fat grafting procedure a durable result can be achieved, persisting for a minimum of 12 months without any trend towards reabsorption.

Influence of Corpus Callosum Damage on Cognition and Physical Disability in Multiple Sclerosis: A Multimodal Study

Background Corpus callosum (CC) is a common target for multiple sclerosis (MS) pathology. We investigated the influence of CC damage on physical disability and cognitive dysfunction using a multimodal approach. Methods Twenty-one relapsing-remitting MS patients and 13 healthy controls underwent structural MRI and diffusion tensor of the CC (fractional anisotropy; mean diffusivity, MD; radial diffusivity, RD; axial diffusivity). Interhemisferic transfer of motor inhibition was assessed by recording the ipsilateral silent period (iSP) to transcranial magnetic stimulation. We evaluated cognitive function using the Brief Repeatable Battery and physical disability using the Expanded Disability Status Scale (EDSS) and the MS Functional Composite (MSFC) z-score. Results The iSP latency correlated with physical disability scores (r ranged from 0.596 to 0.657, P values from 0.004 to 0.001), and with results of visual memory (r = −0.645, P = 0.002), processing speed (r = −0.51, P = 0.018) and executive cognitive domain tests (r = −0.452, P = 0.039). The area of the rostrum correlated with the EDSS (r = −0.442, P = 0.045). MD and RD correlated with cognitive performance, mainly with results of visual and verbal memory tests (r ranged from −0.446 to −0.546, P values from 0.048 to 0.011). The iSP latency correlated with CC area (r = −0.345, P = 0.049), volume (r = −0.401, P = 0.002), MD (r = 0.404, P = 0.002) and RD (r = 0.415, P = 0.016). Conclusions We found evidence for structural and microstructural CC abnormalities associated with impairment of motor callosal inhibitory conduction in MS. CC damage may contribute to cognitive dysfunction and in less extent to physical disability likely through a disconnection mechanism.

OUTCOME OF TRANSORAL LASER MICROSURGERY FOR T2-T3 TUMORS GROWING IN THE LARYNGEAL ANTERIOR COMMISSURE

To evaluate the outcomes of transoral laser microsurgery (TLM) in the treatment of T2 to T3 laryngeal carcinomas growing in the laryngeal anterior commissure.