In mucopolysaccharidosis I, deficiency of alpha-L-iduronidase can cause spinal cord compression (SCC) due to storage of glycosaminoglycans (GAGs) within the cervical meninges. As intravenous enzyme replacement therapy (ERT) is not likely to provide enzyme across the blood-brain barrier, standard treatment for this complication is usually surgical, which has a high morbidity and mortality risk. We report on the use of intrathecal (IT) laronidase in a MPS I patient with SCC who refused the surgical treatment. Assessments were performed at baseline, with clinical and biochemical evaluations, 4-extremity somatosensory evoked potentials, 12 min walk test and MRI studies of the CNS. Changes on these parameters were evaluated after 4 IT infusions of laronidase administered monthly via lumbar puncture. To our knowledge, this was the first MPS patient who received IT ERT. No major adverse events were observed. There were no clinically significant changes in serum chemistries. CSF GAG results revealed pretreatment values slightly above normal standards: 13.3 mg/L (NV < 12 mg/L) which after IT laronidase infusions were within normal levels (10.3 mg/L). 12MWT presented a 14% improvement, with better performance on stability and gait control. Maximum voluntary ventilation showed 55.6% improvement considering the percentage of predicted (26.7% at baseline compared to 41.9%); Maximum Inspiration Pressure improved 36.6% of predicted (26.8% at baseline to 36.7%); Pulmonary diffusion improved 17.6% of predicted %. In conclusion, although the improvement observed in this case with IT laronidase should be confirmed in further patients, this procedure seems to be a safe treatment for SCC in MPS I.

Our data showed that white matter lesion is more extensive as disease duration increases, especially in mucopolysaccharidosis type II patients. MRI and magnetic resonance spectroscopy findings did not correlate with either enzymatic or glycosaminoglycan levels.

We report the clinical and radiological central nervous system (CNS) findings of 8 Fabry disease patients, before (8/8) and after (7/8) 12 months of enzyme replacement therapy (ERT) with agalsidase-alpha. Eight biochemically proven Fabry disease patients (from four families) were included. Patients were evaluated at baseline and at regular intervals during 12 months of ERT. Evaluations included a thorough, standardized neurological examination, and magnetic resonance imaging (MRI) and angiography (MRA). Brain proton magnetic resonance spectroscopy (MRS) was also performed in 5/8 patients. The presence and location of grey- and white-matter lesions, the presence of vascular occlusion or ectasia on MRA and the metabolite ratios on MRS were determined, as well as their relation to age, symptoms and neurological examination. Neurological examination showed few abnormalities in these patients: scores varied (on a 0-100 scale) from zero to 5, at baseline and in the 12th month of ERT. The most consistent findings on MRI were asymmetric, widespread patterns of deep white-matter (WM) lesions, hyperintense on T2 and FLAIR-weighted images, found in 4/8 patients at baseline, predominantly in frontal and parietal lobes. These lesions did not correlate with other clinical variables, although there was a trend towards an association of the lesions with age and hearing loss. The youngest patient with MRI lesions was 24 years old. After 12 months of ERT, MRI was normal in 3/7, showed the same WM lesions in 2/7, and showed worsening of WM lesions in 2/7 patients (from the same family). Abnormal MRS metabolite ratios were detected at baseline in 4/5 patients. While neurological examination remained almost normal during the 12 months of ERT, new small-vessel CNS involvement still appeared in 2/7 patients. We do not know why ERT was not able to prevent this in these two related male patients. This could be due either to their older ages (46 and 36 years), or to a more pathogenic mutation. We conclude that MRI was more sensitive than neurological examination in detecting CNS involvement and progression in Fabry disease in the time interval studied.

This study investigates the relationship between objective cognitive impairment (OCI), subjective cognitive complaints and depressive symptoms in men and women with classical and non-classical Fabry disease (FD). Cognitive functioning was assessed using a neuropsychological test battery, subjective cognitive complaints using a structured interview and depressive symptoms using a depression scale (CESD). Eighty-one patients were included (mean age 44.5 ± 14.3, 35% men, 74% classical). Subjective cognitive complaints were reported by 64% of all patients. OCI was present in thirteen patients (16%), predominantly in men with classical FD. Thirty-one patients (38%) had a high score (≥16) on the CESD scale. Male sex (OR, 6.8; 95%CI, 1.6–39.8; p = 1.6 * 10−2) and stroke (OR, 6.4; 95% CI, 1.1–41.0; p = 3.7 * 10−2) were independently positively associated with OCI, and premorbid IQ (one IQ point increase: OR, 0.91; 95%CI, 0.82–0.98; p = 3.8 * 10−2) was independently negatively associated with OCI. The CESD-score (one point increase: OR, 1.07; 95% CI, 1.02–1.13; p = 3.3 * 10−3) and a history of depression (OR, 2.7; 95% CI, 1.1–7.3; p = 3.9 * 10−2) were independently positively associated with subjective cognitive complaints. OCI is present in 16% of FD patients, warranting referral for neuropsychological assessment. Nevertheless, subjective cognitive complaints are related to depressive symptoms, emphasizing the importance of recognition and treatment of the latter.

These guidelines are a result of several meetings from the Brazilian Stroke Society (Sociedade Brasileira de Doenças Cerebrovasculares -SBDCV, website www.sbdcv.org.br), which represents the Scientific Department in cerebrovascular diseases of the Brazilian Academy of Neurology, responsible for technical opinions and educational projects related to cerebrovascular diseases. Members from SBDCV participated in web-based discussion forum with pre-defined themes, followed by a formal onsite meeting in which controversies and final position statements were discussed. Finally, a writing group was created to revise and translate the final document, which was approved by all members of the SBDCV. The final text aims to guide specialists and non-specialists in stroke care in managing patients with acute ischemic stroke. The hemorrhagic stroke guideline has been previously published by the same group 1 . In the final recommendations, Oxford classification for evidence level and recommendation grade was used: EVIDENCE LEVELS1. Randomized controlled clinical trial (RCT) or systematic review (SR) of RCT with clinical endpoints. 2. RCT or SR of lower quality: with substitute, validated endpoints; with subgroup analysis or with a posteriori hypotheses; with clinical endpoints, but with methodological flaws.3. RCT with substitute, non-validated endpoints case-control studies. 4. Study with clinical endpoint, but with a higher potential bias (as in experiment without comparison group and other observational studies). 5. Representative forum or expert opinion without abovementioned evidence. RECOMMENDATION GRADESA Systematic review (homogeneous) of RCT; or single RCT with narrow confidence interval; or therapeutic results of "all or nothing" type. B Systematic review (homogeneous) of cohort studies; or cohort study and RCT of lower quality; or outcomes research or ecological study; or systematic review (homogeneous) of case-control studies; or case-control study. C Case reports (including cohort or case-control study of lower quality). D Expert opinion without critical evaluation, based on physiological or animal studies.In this first part of the guidelines, specific topics included were: epidemiology, stroke as a medical emergency, education, pre-hospital management, emergency management, neuroimaging and laboratory evaluation. A translated version of these guidelines in Portuguese is available in the Society's webpage (www.sbdcv.org.br).