Myelin imaging measures as predictors of cognitive impairment in MS patients: A hybrid PET-MRI study.

BACKGROUND: Cognitive impairment is one of the concerns of Multiple Sclerosis (MS) and has been related to myelin loss. Different neuroimaging methods have been used to quantify myelin and relate it to cognitive dysfunctions, among them Magnetization Transfer Ratio (MTR), Diffusion Tensor Imaging (DTI), and, more recently, Positron Emission Tomography (PET) with 11C-PIB. OBJECTIVE: To investigate different myelin imaging modalities as predictors of cognitive dysfunction. METHODS: Fifty-one MS patients and 24 healthy controls underwent clinical and neuropsychological assessment and MTR, DTI (Axial Diffusion-AD and Fractional Anisotropy-FA maps), and 11C-PIB PET images in a PET/MR hybrid system. RESULTS: MTR and DTI(FA) differed in patients with or without cognitive impairment. There was an association of DTI(FA) and DTI(AD) with cognition and psychomotor speed for progressive MS, and of 11C-PIB uptake and MTR for relapsing-remitting MS. MTR in the Thalamus (ß= -0.51, p = 0.021) and Corpus Callosum (ß= -0.24, p = 0.033) were predictive of cognitive impairment. DTI-FA in the Caudate (ß= -26.93, p = 0.006) presented abnormal predictive result. CONCLUSION: Lower myelin content by 11C-PIB uptake was associated with worse cognitive status. MTR was predictive of cognitive impairment in MS.

A preliminary study revealing a new association in patients undergoing maintenance hemodialysis: manganism symptoms and T1 hyperintense changes in the basal ganglia.

BACKGROUND AND PURPOSE: Patients undergoing parenteral nutrition and those with portosystemic encephalopathy secondary to chronic liver disease and acquired and congenital portosystemic venous shunts frequently present manganese deposition in the basal ganglia, detected by MR imaging as hyperintense areas on T1-weighted sequences. We also observed similar abnormalities in the basal ganglia of patients with chronic renal failure undergoing maintenance hemodialysis. Our aim was to evaluate the pallidal signal intensity on T1-weighted images in a series of patients undergoing hemodialysis, with further evaluation of serum manganese levels and neurologic correlation, comparing them with patients with chronic renal failure without dialytic treatment. MATERIALS AND METHODS: We performed MR imaging examinations in 9 patients with chronic renal failure, 5 of whom were undergoing hemodialysis. An experienced neuroradiologist scrutinized the presence of symmetric hyperintensities in the basal ganglia on T1-weighted sequences. We also determined the serum manganese levels and performed the neurologic evaluations in all patients. RESULTS: All patients undergoing hemodialysis presented elevated serum manganese levels and symmetric hyperintensities within the globus pallidus. In this group, 4 patients presented with parkinsonian symptoms, myoclonus, and syndromes with vestibular and vestibular-auditory symptoms. The patients without dialytic treatment presented with neither bilaterally increased T1 MR imaging signal intensity within the globus pallidus nor symptoms of manganism. CONCLUSION: Our preliminary results demonstrated the occurrence of bilateral pallidal hyperintensity on T1-weighted images in all patients undergoing hemodialysis associated with high serum manganese levels, revealing a new association.

Diuretic, natriuretic and kaliuretic effects of dexamethasone.

We report the diuretic, natriuretic and kaliuretic effects of dexamethasone (DEXA) on intact and adrenalectomized (ADX) male Wistar rats. Indomethacin (INDO) and spironolactone were used to evaluate the involvement of prostaglandin and mineralocorticoid receptors in these actions. DEXA (400 micrograms/kg) and INDO (20 mg/kg) were injected iv and spironolactone (8 mg/100 g) was administered by the oral route. The parameters analyzed were urinary volume (UV), sodium excretion (UNaV) and potassium excretion (UKV). DEXA increased UV and UKV in both intact and ADX rats. INDO administered to intact rats reduced UV by 28% (P less than 0.05) and caused anuresis in ADX rats, but did not interfere with the increased UV induced by DEXA in either ADX or intact animals. Spironolactone did not interfere with diuretic parameters in control animals, but in DEXA-treated animals it decreased UKV by 30% and inhibited DEXA-induced diuresis. These data rule out the possibility of prostaglandin involvement in the acute effects of DEXA and suggest that DEXA induces diuresis through its action on mineralocorticoid receptors or on specific receptors for glucocorticoid (the type II receptor). The latter might also be inhibited by spironolactone.

[Fatigue and multiple sclerosis: preliminary study of 15 patients with self-reported scales]. / Fadiga e esclerose múltipla: estudo preliminar de 15 casos através de escalas de auto-avaliação.

Fatigue is a common and disabiling symptom in multiple sclerosis but is poorly understood. Self-report measures are designed to capture the patient's subjective sense of fatigue. We applied three scales in 15 patients with MS. Nine of them reported fatigue. The scores were high in all of these patients. We conclude that these scales must be used in assemble, to evaluate this symptom. Also, fatigue a very important symptom in multiple sclerosis patients.

[Multiple sclerosis: descriptive study of its clinical forms in 302 cases]. / Esclerose múltipla: estudo descritivo de suas formas clínicas em 302 casos.

Multiple sclerosis (MS) is one of the most common causes of chronic neurologic disability in young adults. We evaluate, through retrospective study, the epidemiological characteristics, the manifestations ways, the clinical manifestations, the evolution and the level of physical disability of MS in 302 patients. The average patients age was 37.7 and the relation between genders was 3.13F:1M. The average age at the beginning of MS was 29.6; 283 patients were white (94%), 15 patients were black (5%) and 4 patients were yellow; 220 patients (72%) presented relapsing-remmiting clinical form; 82 patients (28%) presented the progressive form (50% secondary form and 50% primarily progressive form). The most common initial symptoms were sensitive (31.7%) and optical (26.8%). The most common evolutive symptoms were pyramidal (72.5%) and of the spinal cord (64.9%). The average of the final EDSS was 3.37 and final NRS was 85.17. The index of the annual outbreak was 0.45. Our findings coincide to the ones in the worldwide literature, however it is important to point out that 60 patients (19.8%) presented benign MS of prognostic value.

[Comparative analysis of 2 clinical scales for clinical evaluation in multiple sclerosis: review of 302 cases]. / Análise comparativa entre duas escalas de avaliação clínica na esclerose múltipla: revisão de 302 casos.

Many neurologic scales have been used for clinical evaluation of multiple sclerosis, but there is no consensus about which one is the most appropriate to assess evolution and point to a new relapse. The Expanded Disability Status Scale (EDSS) has been the most commonly used. We analyse the reliability of two scales: the EDSS and Neurologic Rating Scale (NRS) in 302 multiple sclerosis patients. It is shown that NRS is a more sensitive scale than EDSS to disclose clinical changes (22.1% of cases). Changes in NRS were more evident in patients with EDSS 3.0 and 3.5. We comment on these findings and suggest that both scales should be employed in multiple sclerosis treatment trials.

[Chorea: clinical analysis of 119 cases]. / Coréia. Análise clínica de 119 casos.

Chorea is a clinical syndrome characterized by abnormal involuntary arrhythmic movements, randomly distributed in time, affecting mainly the distal parts of the limbs. There are many diseases associated with chorea but the distribution of the etiologies vary too much in different parts of the world. We intended to study the etiologies of chorea in a Movement Disorders Unit of a university hospital-based outpatient clinic in Brazil. We studied the records of 119 patients with chorea based in the diagnostic criteria of the World Federation of Neurology. Sydenham's chorea (SC) was the most frequent cause of chorea (51.3%) of our sample. Other common causes were Huntington's chorea (18.5%) and chorea post-stroke (9.2%). SC is not commonly seen in developed countries nowadays but is not rare in Brazil. SC patients generally have the clinical manifestation of it in the first 20 years of age and girls are more affected than boys and this feature was observed in our sample. Based on our own experience and in the review of the literature we propose an etiological classification of chorea.

[Box and block test of manual dexterity in normal subjects and in patients with multiple sclerosis]. / Teste de destreza manual da caixa e blocos em indivíduos normais e em pacientes com esclerose múltipla.

Recently new disease-modifying treatments for multiple sclerosis (MS) were introduced which can change the natural course of the disease. In clinical trials with these new agents the Expanded Disability Status Scale (EDSS) is often used as a primary outcome instrument to measure neurological impairment and disability. A number of limitations have been identified when using the EDSS, some of wich are because the EDSS is an ordinal scale that is heavily biased to locomotor function. In this study we applied the box and block test of manual dexterity in normal subjects and relapsing-remitting MS patients. The results were that 64.8% of the female and 80.7% of the male patients had significant changes on this task compared with normal subjects, and as this test is easily applied and is sensitive in detecting upper extremity functional ability, we recommend its use in clinical trials to evaluate new drugs in MS patients.

[Interferon beta 1-a in multiple sclerosis: 1-year experience in 62 patients]. / Interferon beta 1-a na esclerose múltipla: experiência de um ano em 62 pacientes.

We report the results of a trial of interferon beta 1-a in 62 ambulatory patients with relapsing-remitting multiple sclerosis. Entry criteria included EDSS of 0 to 5.5 and at least two exacerbations in the previous 2 years. The patients received 3 million international units by subcutaneous injections three times a week. The end points were differences in exacerbation rate and treatment effect on disease progression. The annual exacerbation rate for patients that did not take the interferon beta 1-a was 1.32 and for the patients under medication 0.63. The EDSS score in patients that did not take the mediaction was 4.7 and 2.0 for the patients with interferon beta 1-a. Interferon beta 1-a was well tolerated and 85% of patients completed 1 year treatment.

[Recommendations for the use of immunomodulatory drugs in multiple sclerosis: the BCTRIMS consensus] [Brazilian Committee for Treatment and Research in Multiple Sclerosis]. / Recomendações quanto ao uso de drogas imunomoduladoras na esclerose múltipla: o consenso do BCTRIMS.

After brief considerations about clinical course and diagnosis in multiple sclerosis, the members of the BCTRIMS present some recommendations for the use of the immunomodulatory drugs in the treatment of this disease.

[Fatigue in multiple sclerosis relapsing-remitting form]. / Fadiga na forma remitente recorrente da esclerose múltipla.

In 95 patients with the remitting-relapsing form of multiple sclerosis we investigated fatigue. All of them were evaluated with the Fatigue Severity Scale and we found it in 64 patients (67.4%). Gender, age, depression and fuctional incapacity was not predictive of fatigue occurrence, while anxiety and time of disease seems to be correlated with it. When we analysed the fatigue severity, a correlation between the EDSS and the increasing fatigue severity was found.

[Historical aspects of multiple sclerosis]. / Aspectos históricos de la esclerosis múltiple.

INTRODUCTION: Multiple sclerosis (MS) is one of the most common diseases of the central nervous system (CNS) in young adults. MS is the most common disorder of the central nervous system in young people living in temperate climate regions. Although a few references to possible cases of the disease come from the xiii century, its scientific observation and systematic study only started in the late xix century. DEVELOPMENT: Robert Carswell e Jean Cruveilhier were the first investigators to document the pathological lesions while the clinical picture was first studied by Charcot. In spite of a huge number of infectious agents has been proposed for the etiology of MS and a genetic susceptibility trait recently defined, the ultimate cause of the disease remains to be determined. The development of diagnostic criteria sets, clinical disability scales and image methods in the latter half of the last century has provided investigators with useful research tools allowing unprecedented advances. In the last 30 years ACTH and corticosteroids have been employed as treatment for MS relapses. Starting in 1993 a new class of drugs called disease modifying agents, such as interferon beta and more recently glatiramer acetate, was introduced with encouraging results. CONCLUSIONS: MS is postulated to be a cell mediated autoimmune disease directed against CNS myelin components and characterized by inflammation and chronic demyelination. This paper is a review of the principal most significant events in the search for knowledge of the disease in the world.

[Simple epidermolysis bullosa. Anatomo-clinical considerations with respect to 7 cases]. / Epidermólise bolhosa simples. Considerações anatomo-clínicas a respeito de sete casos.

Seven patients, belonging to seven different families, are reported. The clinical picture is dominated by the bullous lesions which appeared during the delivery or soon after birth; in one patient (case 4) the lesions first appeared after the first year of life. Besides the bullae there were erosions, crusts, residual macules but no millia cysts or scars. The nails were affected in several patients; the mucosae were affected in 2 patients. The histological aspects of the lesions are described; in all the cases it was possible to establish the position of the cleavage in regard to the functional membrane. The patients were treated with many different kinds of treatment which included topical and systemic corticotherapy; recently alpha-tocopherol (Roche) was assayed; none of the medicaments showed efficacy. The management of the patients relies on protective measures in order to avoid the formation of new lesions; gentle and time consuming nursing care is necessary to treat the patients. This must be explained to the parents of the patients as the care will rely on them. It is important to explain also the basic cutaneous defect that provokes the skin trouble and the necessity to avoid trauma and the possibility of the appearance of a new child with the defect in any subsequent pregnancy. The situation improves with age and this form of E.B. is compatible with a normal adult life.

The Brazilian database on pregnancy in multiple sclerosis.

OBJECTIVES: To report the results from the Brazilian database on multiple sclerosis (MS) and pregnancy. METHODS: Retrospective data from MS patients who became pregnant at any time of their disease were sent to a Brazilian database, using a specific file for this purpose. RESULTS: Data on 128 women (142 pregnancies) from 30 neurologists working in 21 cities in Brazil were collected. Patients' average age at pregnancy was 29.8 years (range 16-42). EDSS at start of pregnancy was 1.5±1.4; and the relapse rate in the year preceding pregnancy was 1.2±1.5. Exposure to medication at any time during pregnancy was high (69.7%): 48.6% to interferon beta; 14.1% to glatiramer acetate; and 7% to other immunomodulatory and immunosuppressive drugs. There was a significant decrease in relapse rate during pregnancy. The prevalence of complications was relatively low, with 4.9% of obstetric and 1.4% neonatal unfavorable outcomes. CONCLUSIONS: Our patients had low degrees of disability, short histories of disease, high drug exposure, and relatively high relapse rate in the year previous to pregnancy. Obstetric and neonatal outcomes were successful in over 90% of our patients.

Fatigue in a cohort of geriatric patients with and without Parkinson's disease.

We evaluated the frequency of fatigue in geriatric patients with and without Parkinson's disease (PD) and correlated it with depression and excessive daytime sleepiness. We evaluated 100 patients from Hospital São Paulo, 50 with PD from the Neurologic Outpatient Clinic and 50 with non-neurologic diseases or oncologic diseases from the Geriatric Outpatient Clinic (controls). All patients who scored 28 or more on the Fatigue Severity Scale (FSS) were considered to have fatigue. Also, all patients were submitted to a structured interview to diagnose depression by the criteria of the American Psychiatric Association (DSM-IV, 4th version) and were evaluated by the Modified Impact of Fatigue Scale and the Epworth Sleepiness Scale (ESE) to detect excessive daytime sleepiness. Demographic and disease details of all PD patients were recorded and the patients were examined and rated by the Unified Parkinson's Disease Rating Sale (UPDRS) and Hoehn-Yahr staging. Frequency of fatigue (FSS >or=28) was 70% for PD and 22% for controls. Twenty of 35 PD patients with fatigue had concomitant depression. Compared to controls, PD patients were found more frequently to have depression by DSM-IV criteria (44 vs 8%, respectively) and excessive daytime sleepiness by the ESE (44 vs 16%), although only depression was associated with fatigue. Fatigue was more frequent among depressed PD and control patients and was not correlated with PD duration or with UPDRS motor scores. ESE scores did not differ between patients with or without fatigue.

Trigeminal involvement in multiple sclerosis: magnetic resonance imaging findings with clinical correlation in a series of patients.

Trigeminal involvement detected by magnetic resonance imaging (MRI) in multiple sclerosis (MS) patients is usually associated with trigeminal neuralgia (TN) or painless paraesthesia in the trigeminal distribution. Our aim is to review the incidence of trigeminal involvement on MRI in a series of patients with MS at our institution, with further clinical correlation. We reviewed MRI scans of 275 MS patients for the presence of gadolinium enhancement on postcontrast T1-weighted images, anatomical and signal abnormalities on different sequences at the pontine trigeminal root entry zone (REZ) and in the cisternal portion of the nerves. We observed enhancement in the cisternal portion of the nerves and signal abnormalities (with or without enhancement) at the pontine trigeminal REZ in 8 (2.9%) patients, and enhancement was bilateral in 6 (75%) of those. Despite the inflammatory activity, none of them had TN and 3 (37.5%) had only painless paraesthesias in the correspondent V3 distribution. We also found a marked trigeminal hypertrophy in 2 (25%) patients, both with a longer period of disease. Our results confirm a high and clinically silent incidence of trigeminal involvement in MS patients, and suggest a simultaneous role of the central and peripheral type of myelin in trigeminal demyelination.

A bacteriological survey of washrooms and toilets.

A survey of the bacterial flora present at various positions in 130 male and female washrooms and toilets is reported. Several bacteria of faecal origin were found in large numbers: the areas likely to be the most important sources of cross-infection from faecal contamination are indicated. The results are used to assess priorities for disinfection.