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.

Beyond weakness: Characterization of pain, sensory profile and conditioned pain modulation in patients with motor neuron disease: A controlled study.

BACKGROUND: Motor neuron diseases (MND) represent a group of disorders that evolve with inexorable muscle weakness and medical management is based on symptom control. However, deeper characterization of non-motor symptoms in these patients have been rarely reported. METHODS: This cross-sectional study aimed to describe non-motor symptoms in MND and their impact on quality of life and functional status, with a focus on pain and sensory changes. Eighty patients (31 females, 55.7 ± 12.9 years old) with MND underwent a neurological examination, pain, mood, catastrophizing and psychophysics assessments [quantitative sensory testing (QST) and conditioned pain modulation (CPM)], and were compared to sex- and age-matched healthy controls (HC). RESULTS: Chronic pain was present in 46% of patients (VAS =5.18 ± 2.0). Pain of musculoskeletal origin occurred in 40.5% and was mainly located in the head/neck (51%) and lower back (35%). Neuropathic pain was not present in this sample. Compared to HC, MND patients had a lower cold detection threshold (p < 0.002), and significantly lower CPM scores (4.9 ± 0.2% vs. 22.1 ± 0.2%, p = 0.012). QST/CPM results did not differ between MND patients with and without pain. Pain intensity was statistically correlated with anxiety, depression and catastrophism, and spasticity scores were inversely correlated with CPM (ρ = -0.30, p = 0.026). CONCLUSIONS: Pain is frequently reported by patients with MNDs. Somatosensory and CPM changes exist in MNDs and may be related to the neurodegenerative nature of the disease. Further studies should investigate the most appropriate treatment strategies for these patients. SIGNIFICANCE: We report a comprehensive evaluation of pain and sensory abnormalities in motor neuron disease (MND) patients. We assessed the different pain syndromes present in MND with validated tools, and described the QST and conditioned pain modulation profiles in a controlled design.

Recurrent neuromyelitis optica in Brazilian patients: clinical, immunological, and neuroimaging characteristics.

Neuromyelitis optica has not been thoroughly studied in Brazilian patients following the discovery of NMO-IgG and its specific antigen aquaporin-4. In this study we aimed to describe the clinical NMO-IgG immunological status and neuroimaging characteristics of recurrent neuromyelitis optica in a series Brazilian patients. We undertook a retrospective study of 28 patients with recurrent neuromyelitis optica, according to 1999 Wingerchuk's diagnostic criteria. Data on NMO-IgG status, clinical features, and MRI findings were analyzed. Three men and 25 women were evaluated. Median age at onset of disease was 26 years (range 7-55); median time of follow-up was 7 years (range 2-14). The mean time elapsed between the first and the second attack was 17 months (median 8.5; range 2-88). NMO-IgG was detected in 18 patients (64.3%). Four patients died due to respiratory failure. Most patients presented with cervical (36%) and cervical-thoracic myelitis (46.4%). Holocord lesion was the most common pattern of involvement (50%) on the axial plane. We did not find a statistical association between myelitis extension and NMO-IgG result. Our series of Brazilian patients showed a younger age of onset than previously reported. In our series, in contrast to previous reports, there was no correlation between the extension of myelitis and NMO-IgG positivity.

Correlation of magnetization transfer and diffusion magnetic resonance imaging in multiple sclerosis.

The aim of this study was to correlate diffusion to magnetization transfer (MT) magnetic resonance imaging (MRI) results in multiple sclerosis (MS), in order to establish if the former technique provides complementary information. Magnetization transfer ratio (MTR) and apparent diffusion coefficient (ADC) were measured in 156 different regions of interest (ROIs) of 14 MS patients, where 84 corresponded to T1 hypointense lesions, 60 to T1 isointense lesions and 12 to regions of normal appearing white matter (NAWM). MTR mean value was higher for T1 isointense than for T1 hypointense lesions, and lower when compared to NAWM. ADC mean value for T1 isointense lesions was higher than for NAWM, but lower than for T1 hypointense lesions. A significant negative correlation was found between ADC and MTR for hypointense lesions (Pearson's r = -0.758, P < 0.001), whereas this correlation was much weaker for T1 isointense lesions (Pearson's r= -0.256, P = 0.049). There was no correlation between ADC and MTR for NAWM. The fact that ADC and MTR show a strong correlation only for T1 hypointense lesions indicates that, when tissue integrity is not severely compromised, as in the case of T1 isointense lesions or NAWM, ADC and MTR might be sensitive to different pathological processes.

[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.

The prevalence of multiple sclerosis in the city of São Paulo, Brazil, 1997.

July 1, 1997 was stipulated as the day for estimating the prevalence of multiple sclerosis within the city of São Paulo. The patients were identified via various sources, including associated universities and magnetic resonance services of the city of São Paulo. The area covered by the study has a population of 9,380,000, mainly white and of European origin, with a large number of immigrants from Spain and Portugal. The patients were classified in accordance with the criteria of Poser et al. (1983), and only those with defined multiple sclerosis were registered. The study gave a prevalence of 15.0/10(5) inhabitants, or three times the value obtained in a similar study in 1990. This increase reveals the larger number of cases encompassed by the study, and is attributed to the use of more detailed recording methods, improvements in diagnosis, and better conditions for treatment.

Amyotrophic lateral sclerosis in Brazil: 1998 national survey.

OBJECTIVES: To assess the epidemiologic characteristics of amyotrophic lateral sclerosis (ALS) in Brazil in 1998. METHOD: Structured Clinical Report Forms (CRFs) sent to 2,505 Brazilian neurologists from January to September 1998 to be filled with demographic and clinical data regarding any ALS patient seen at any time during that year. RESULTS: Five hundred and forty CRFs were returned by 168 neurologists. Data on 443 patients meeting the criteria of probable or definite ALS according to El Escorial definition were analysed: 63 probable (14.2%) and 380 definite (85. 8%). Two hundred and fifty-nine (58.5%) of the patients were male, mean age of onset was 52. Spinal onset occurred in 306 patients (69%); bulbar onset in 82 (18.5%), and both in 52 (11.7%). Twenty-six (5.9%) had a family history of ALS. Two hundred and fifty-nine (58.6%) were seen by private practitioners, and 178 (40. 2%) at a hospital clinic. Age-ajusted incidence shows a peak incidence at the 65-74 years old range. CONCLUSIONS: The disease's characteristics are similar to those described in international studies, except for age of onset (Brazilian patients are younger). This difference is not confirmed when figures are age-adjusted.

Magnetic resonance imaging in five patients with a tumefactive demyelinating lesion in the central nervous system.

Five patients with a tumefactive lesion were clinically followed from 1992 to 1993. Four patients were female; age ranged from 32 to 57 years, the duration of symptoms varied from 3 days to 3 years. Neurological examination disclosed dementia in two patients, aphasia in three, hemiparesis in four, hemihypoaesthesia in three, optical neuritis in two, tetraparesis with sensitive level and neurogenic bladder in one. MRI disclosed lesions with a hypersignal on images assessed at T2 and hyposignal at T1, and gadolinium heterogeneous enhancement; these lesions were located in the: a) temporooccipital region bilaterally and brain stem, b) frontoparietal white matter, c) basal ganglia, bilateral white matter and brain stem, d) left parietal region, e) cervical spinal cord, with enlargement of this region. Cerebral biopsy was performed in three patients; acute and subacute demyelinating disease was diagnosed by histological examination. Two patients had an evolutive diagnosis; exclusion of other pathologies and clinical and radiological improvement after corticotherapy, pointed to an inflammatory disease.

Creutzfeldt-Jakob disease. A survey of 14 patients.

Creutzfeldt-Jakob disease (CJD) is a transmissible disease of the nervous system causatively related to the presence of an abnormal prion protein, with dementia, myoclonic jerks, and periodic EEG activity. Fourteen patients (7 females and 7 males) ranging from 26 to 76 years of age (median 59 years) were evaluated between 1974 and 1995 at the Neurologic Clinic of São Paulo University School of Medicine. The average duration of the disease was 12 months (3.5-34 months). Early clinical findings were: behaviour changes in 7 patients, dementia in 4, visual disturbances in 4, vertigo in 2, tremor in 9, and dystonia in one. Advanced symptoms were dementia and myoclonus in all patients. Pyramidal tract dysfunction was found in 6, cerebellar ataxia in 2, seizures in 3, nystagmus and vertigo in 4, and peripheral nervous system involvement in 2. Atypical clinical forms were found in 5 patients. Periodic EEG activity was found in 10 patients. Cerebrospinal fluid evaluation showed pleocytosis in 1 patient, higher protein content in 2, and higher gamma globulin level in 2. In 10 patients anatomopathological evidence in the central nervous system confirmed the clinical diagnosis by presenting with status spongiosus. All except one patient presented with the sporadic form of the disease.

Pediatric multiple sclerosis report of 14 cases.

We present clinical data from 14 multiple sclerosis (MS) patients who have been admitted to our hospital between January 1980 and May 1992, whose age of onset ranged from 2-15 years. Our patients could be classified as having a clinically definite form of the disease. Initial symptoms varied from minor, such as motor or sensory impairment, bladder dysfunction, to the worst clinical presentation, suggesting diffuse encephalopathy. All the patients had a relapsing-remitting course. We report the paraclinical and laboratory examinations that were done in these patients. Over the period 1980 to 1992 these patients had 39 attacks. CSF analysis was performed in the phase of activity of the disease on 23 occasions and was normal in 12. At least one brain CT scan was performed in 9 patients and showed white matter abnormalities in 6. Cranial magnetic resonance imaging was done in 6 patients and were abnormal in 5. Visual evoked potential (EP) was abnormal in 7 of 8 patients; brainstem acoustic EP was abnormal in 4 of 8 patients and somatosensory EP in 4 of 8. MS is not so rare in childhood and although its diagnosis is essentially a clinical one, paraclinical investigations are of great value in the identification of demyelinating disorders in childhood.

Prevalence of multiple sclerosis in the city of São Paulo, Brazil, in 1990.

A case register of multiple sclerosis (MS) was set up in the city of São Paulo, Brazil, situated at a latitude of 23-24 degrees south. Cases were notified by neurologists, neuroradiologists and by an association of patients with MS. Prevalence rate was 4.27 x 10(-5) (men: 2.89 x 10(-5); women: 5.59 x 10(-5)), with a preponderance of young adults. We discuss here whether these rates are artifact due to poor health care facilities, to poor notification and deficiencies in diagnosis, or whether these rates are really low.

Cerebrospinal fluid and serum antiphospholipid antibodies in multiple sclerosis, Guillain-Barré syndrome and systemic lupus erythematosus.

Immunoglobulins isotypes (IgG and IgM) for myelin basic protein (MBP), cerebrosides (CER), gangliosides (GANG) and cardiolipin (CARD) were detected in the cerebrospinal fluid (CSF) from 33 patients with multiple sclerosis (MS), 18 with Guillain-Barré syndrome (GBS) and 30 with systemic lupus erythematosus (SLE). In MS patients occurred positive and significant levels of IgG-MBP in 51.5% (p less than 0.05) and IgM-MBP in only 18.2%, IgG-CARD in 46.2%, as long as CER and GANG were detected in almost 20%. From serum samples of MS patients 20.6% presented IgG-MBP, while 53% showed positive levels for IgM-MBP. The CSF analysis of patients with GBS showed that 56.3% revealed IgG-MBP (p less than 0.05), 53% for IgM-MBP, 38.5% for IgG-CER and 23% for IgM-CER, while 50% of patients had IgG-CARD, as long as 31% also had IgG-GANG. The serum evaluation from 14 patients showed that 18.8% had positive concentrations of IgG-MBP and 56.3% presented IgM-MBP (p less than 0.05). Except for 50% of patients with SLE who presented positive CSF levels of IgG-CARD, only 24.1% had positive levels of IgG-MBP. We believe that the presence of antiphospholipid antibodies in CSF of the above mentioned diseases occurred as immune epiphenomena, but their appearance would permit the maintenance of and perpetuate the immune event.

Cerebrospinal fluid and serum antiphospholipid antibodies in multiple sclerosis, Guillain-Barré syndrome and systemic lupus erythematosus

Isotipos de imunoglobulinas (IgG e IgM) de proteína básica de mielina (PBM), cerebrosídeos (CER), gangliosídeos (GANG) e cardiolipina (CARD) foram investigados em amostras de líquido cefalorraquidiano (LCR) de 33 pacientes com esclerose múltipla (EM), 18 com síndrome de Guillain-Barré (SGB), e 30 com lúpus eritematoso sistêmico (LES). Pacientes com EM revelaram concentraçöes positivas e significantes para IgG-PBM em 51,5% (p<0,05), IgM-PBM em 18,2%, IgG-CARD em 46,2%; CER e GANG foram detectados em cerca de 20% dos pacientes. A avaliaçäo dos isotipos de imunoglobulinas no soro de pacientes com EM foi positiva em 20,6% para IgF-PBM e 53,0% para IgM-PBM. No LCR dos pacientes com SGB a análise mostrou-se positiva em 56,3% para IgG-PBM (p<0,05), 53% para IgM-PBM, 38,5% para IgG-CER e 23% para IgM-CER, 50% para IgG-CARD e 31% para IgM-GANG. Os isotipos avaliados no soro de 14 pacientes com SGB foram positivos em 18,8% para IgG-PBM e 56,3% para IgM-PBM (p<0,05). No LCR, 50% dos pacientes com LES revelaram positividade para IgG-CARD e 24,1% para IgG-PBM. Os autores acreditam que a presença de anticorpos antifosfolípides seja conseqüente a epifenômeno imune, embora sua presença possa manter e perpetuar o evento imune intrínseco a essas doenças

HTLV-I associated myelopathy in Brazil: a preliminary report.

In this preliminary report the authors present the finding of a high prevalence (37.5%) of seropositivity of antibodies to HTLV-I tested by Western blotting in a sample of 16 Brazilian patients with chronic myelopathies of undetermined origin.

HTLV-I associated myelopathy in Brazil: a preliminary report

Neste relato preliminar os autores registram a constataçäo de alta prevalência do soropositividade para anticorpos dirigidos ao HTLV-I detectados pelo método de Westernblot (37,5%) em amostra de 16 pacientes brasileiros com mielopatias crônicas de causa näo determinadas

[Retinal periphlebitis in multiple sclerosis. Report of a case]. / Periflebite retiniana na esclerose múltipla. Relato de um caso.

Sheathing of peripheral retinal veins occurs in 10 to 20% of patients with multiple sclerosis and can be seen at any point in the progression of the disease. This finding may represent the retinal correlate of the vascular lesions that are present in the central nervous system of patients with multiple sclerosis. Its pathogenesis is still uncertain. In this paper it is registered the occurrence of retinal periphlebitis as one of the initial manifestations of a patient with multiple sclerosis and it is discussed the diagnostic implications of this finding.

[Recurrent polyradiculoneuritis: report of 2 cases]. / Polirradiculoneurite recidivante: relato de dois casos.

Two cases of patients with relapsing polyradiculoneuropathy with high protein level in cerebrospinal fluid are reported. The immunological features and the natural history of the relapsing polyradiculoneuropathy are discussed. This disease is considered a particular auto-immune nosologic condition, independent from acute polyradiculoneuropathy.

[Miller Fisher syndrome. Report of a case]. / Sindrome de Miller Fisher. Relato de um caso.

The case of a man 34 year-old presenting upward gaze paralyses and external ophthalmoplegia without involvement of the downward gaze, accompanied by cerebellar disorders, generalized areflexia but no muscular weakness, and moderate sensory impairment of the four extremities is reported. The cerebrospinal fluid showed an albuminocytologic dissociation. Recovery was rapid and almost complete, within 3 weeks, remaining minimal paresis of the upward gaze and lateral movement in both eyes. The improvement had been coinciding with the treatment by cortrosina.