Post-COVID-19 olfactory dysfunction: carbamazepine as a treatment option in a series of cases.

Olfactory dysfunction is reported frequently in patients with coronavirus disease 2019. However, an effective treatment for this dysfunction is unknown. The present study evaluated carbamazepine as a treatment option for olfactory dysfunction based on its use in cases of neuralgia, especially of the V cranial nerve. The study included 10 patients with coronavirus disease with olfactory complaints who were part of a cohort of 172 coronavirus disease patients monitored for late neurological manifestations. Carbamazepine was administered for 11 weeks. The adverse effects reported were drowsiness (9/10) and dizziness (2/10); 9 of the 10 patients reported improved olfactory function after carbamazepine treatment. While the role of carbamazepine in the control of post-coronavirus disease olfactory dysfunction could not be confirmed in this study, the satisfactory response observed in most patients in this series suggests that further studies are warranted.

Cognitive Complaints Assessment and Neuropsychiatric Disorders After Mild COVID-19 Infection.

OBJECTIVES: This study aimed to analyze cognitive impairment associated with long-term coronavirus disease 2019 (COVID-19) syndrome and its correlation with anxiety, depression, and fatigue in patients infected with severe acute respiratory syndrome coronavirus. METHODS: This was a cross-sectional study of 127 patients with COVID-19. Tests to screen for neuropsychiatric symptoms included the Fatigue Severity Scale, Mini-Mental State Exam 2 (MMSE-2), Symbol Digit Modalities Test (SDMT), and Hospital Anxiety and Depression Scale. RESULTS: In cognitive tests, SDMT was abnormal in 22%, being more sensitive than MMSE-2 to detect cognitive changes. Furthermore, although manifestations such as fatigue, depression, and anxiety were frequent in the post-COVID-19 phase, these 3 conditions, known to contribute to cognitive impairment, were slightly correlated with worse performance on the rapid screening tests. CONCLUSIONS: In patients with mild COVID-19 and cognitive complaints, SDMT helped to confirm disturbances in the attention domain and processing speed.

Cavernous sinus medial wall: dural or fibrous layer? Systematic review of the literature.

The cavernous sinus (CS) has one of the most complex anatomical networks of the skull base and because of the diversity of its contents is involved in many pathological processes. Nevertheless, anatomical literature concerning the CS is still controversial, so a systematic literature review was performed to find out the microanatomy of the medial wall of the CS and its clinical importance on sellar pathologies. Experimental studies from English-language literature between 1996 and 2010 were identified in MEDLINE, LILACS, and Cochrane databases. After analysis, two tables were prepared exhibiting the major points of each article. Fourteen experimental studies were included in the tables. Four studies concluded that the medial wall of the CS is composed of a loose, fibrous structure, and the remaining ten presumed that the medial wall is formed by a dural layer that constitutes the lateral wall of the sella. The lack of definition standards and of methodological criteria led to variation in the results among different studies. Thus, this hindered results comparison, possibly explaining the different observations.

Anti-AQP(4) antibody in idiopathic acute transverse myelitis with recurrent clinical course: frequency of positivity and influence in prognosis.

BACKGROUND: The anti-aquaporin4 (anti-AQP4) antibody is specific for neuromyelitis optica (NMO), but is also found in limited forms. The presence of this antibody in acute transverse myelitis (ATM) has been associated with recurrence and conversion to NMO, but the influence on disability has not yet been described. OBJECTIVE: To describe the frequency of anti-AQP4 in ATM and analyze the influence in long-term prognosis. DESIGN: Cross-sectional and retrospective study. METHODS: Consecutive ATM cases in a multiple sclerosis center in Rio de Janeiro, Brazil, from 2000 through 2009 were reviewed. Recurrent cases tested for anti-AQP4 were selected. ATM with magnetic resonance imaging spinal cord lesions extending over three or more vertebral segments was classified as longitudinally extensive transverse myelitis (LETM); Kurtzke scale was applied at last evaluation. OUTCOME MEASURES: Frequency of anti-AQP4; severity of spinal cord dysfunction at last follow-up. RESULTS: Twenty six patients (21 female:5 male; 17 white:9 African descent) were studied. The first ATM occurred at 38.04 ± 12.7 years. The interval between the first and the second ATM was eight months (1-150) and the number of ATM varied from two to seven. After 40.5 months (12-192) of disease, the median Expanded Disability Status Scale (EDSS) score was three (0-9). Anti-AQP4 antibody was positive in 26.9%. LETM was found in 65.4%. LETM presented later onset, higher disability and higher positivity to anti-AQP4 (LETM 41.2% versus no-LETM 0%, P = 0.024). Dysfunction at long-term follow-up was similar in anti-AQP4 positive and negative cases. CONCLUSION: The frequency of anti-AQP4 in recurrent ATM was 26.9%, increasing to 41.2% among LETM. Presence of the antibody had no influence on morbidity.

Optic neuritis in Asian type opticospinal multiple sclerosis (OSMS-ON) in a non-Asian population: A functional-structural paradox.

BACKGROUND: Biomarkers have improved the classification of autoimmune inflammatory disorders, including optic neuritis (ON) as a frequent presentation of multiple sclerosis, neuromyelitis spectrum disorders, MOG antibody-related disease (MOGAD), and opticospinal multiple sclerosis (OSMS). The phenotype of OSMS in non-Asian populations is less well known. OBJECTIVE: We investigated the clinical features and prognosis of OSMS-ON in a Brazilian cohort. METHODS: This was a single-center cohort study of patients from Rio de Janeiro (Brazil) with OSMS. All individuals were MOG- and AQP4-seronegative, clinically diagnosed with ON, and had magnetic resonance imaging-confirmed transverse myelitis (TM). Subjects and healthy controls (HCs) were assessed for visual acuity (logMAR VA), automated perimetry mean deviation (MD), intraocular pressure, and spectral-domain optical coherence tomography (OCT), followed by automated retinal layer segmentation of the peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell and inner plexiform layer (mGCIPL). Receiver operator characteristic curves were plotted and the area under the curve (AUC) was calculated for group comparisons of retinal asymmetry of the pRNFL and mGCIPL. RESULTS: The 30 patients with OSMS were predominantly female and white. The mean age was 48 years (range 20-70 years). Unilateral ON was the index event in 83.3% of patients. Over the average 18-year follow-up period, there were 89 relapses of ON. In individuals with OSMS, the average VA was 0.07±0.14 in the right eye (RE) and 0.13±0.30 in the left eye (LE). The MD was -5.37±5.88 dB and -5.23±3.34 dB for the RE and LE, respectively. There was a significant cumulative loss of VA (p = 0.0003) and MD (p = 0.0001) with a higher number of recurrent episodes. Atrophy of the pRNFL thickness was significant in OSMS (RE, 78.62 ± 16.01 µm; LE, 79.86 ± 13.79 µm) relative to the HC group (RE, 98.87 ± 10.68 µm; LE, 97.87 ± 10.85 µm, p = 0.0001). Likewise, there was significant mGCIPL atrophy in patients with OSMS (RE, 74.96 ± 14.46 µm; LE, 73.88 ± 13.79 µm) relative to the HC group (RE, 90.50 ± 6.74 µm; LE, 90.41± 6.89 µm; p = 0.0001). Retinal asymmetry, inter-eye percentage, and absolute differences accurately separated patients with unilateral ON from HCs (AUC=0.89 and AUC=0.85, respectively). CONCLUSION: A structural-functional paradox was found in OSMS with a high diagnostic value for a novel metric based on retinal asymmetry. The functional visual outcome are excellent despite significant structural damage to the inner retinal layers in patients with a high ON relapse rate and long-term bilateral sequential involvement.

Phantom limb phenomena in cancer amputees.

PURPOSE: The objective of this study was to determine the prevalence of phantom pain and correlated conditions such as phantom sensations and stump pain in a population of cancer patients who had undergone limb amputation. METHOD: A cross-sectional study was carried out in adult patients submitted to limb amputation, who were being followed up at the Physiotherapy Department between April 3 and November 30, 2006. The presence of phantom pain and associated conditions was quantified using a verbal numerical scale. The data obtained were analyzed for means, medians, and proportions with their respective confidence intervals, as appropriate. RESULTS: Seventy-five patients participated in this study, 50 men (66.7%) and 25 women (33.3%). Mean age was 54.4 years (SD +/- 18.5); range 19 to 88 years. The prevalence of phantom pain was 46.7% (95%CI: 35.1 to 58.6), phantom sensation 90.7% (95%CI: 81.7 to 96.2), and surgical stump pain 32.0% (95%CI: 21.7 to 43.8). CONCLUSION: Phantom pain and phantom sensations are highly prevalent among cancer patients. Further studies should be carried out to determine the main factors associated with their onset.

CLINICAL course of acute disseminated encephalomyelitis in adults from Rio de Janeiro: Retrospective study of 23 cases and literature review.

BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is a rare inflammatory demyelinating disorder. Most studies involve white children in developed countries in the northern hemisphere. The authors aimed to describe the clinical course and prognostic of a cohort of adult patients with ADEM from Rio de Janeiro city, where most of the population is Afro-descendant. METHODS: We performed a longitudinal study with retrospective data collection of patients with ADEM seen from 1999 to 2016 at a reference center for demyelinating diseases, identifying demographic, clinical, and laboratory data. Then we compared our findings with data from an extensive review of previously published reports. The literature review was carried out using Google Scholar, PubMed, and the reference lists of included studies. Searches were limited to English language original manuscripts published between 2000 and 2019. RESULTS: Among 1396 registers, we identified 23 cases of ADEM, mostly women (78.3%), Afro-descendant (52.4%) with a mean age of 30.8 ± 11.9 years at onset. One quarter had a previous viral infection and, 4.3% vaccination. The presentation was polyfocal, characterized by the association of pyramidal 82.6%, brainstem 69.6%, mental 65.2%, cerebellar 39.1%, sensory 39.1%, sphincter 43.5%, and visual 34.8% syndromes with severe disability in 86.6%. The breakdown of the blood-brain barrier occurred at 60%. MRI was suggestive of ADEM in 87%, with good radiological evolution. A majority had a significant recovery after treatment. CONCLUSIONS: ADEM in adults is a rare, severe, polyfocal disease with a favorable prognosis. The absence of encephalopathy does not exclude the diagnosis.

Author Correction: A systematic literature review on the European, African and Amerindian genetic ancestry components on Brazilian health outcomes.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Neuromyelitis optica and pregnancy-puerperal cycle.

INTRODUCTION: Since neuromyelitis optic is a disease associated with humoral immunity (Th2), it is speculated that the pregnancy period is associated with increased relapses of the disease, as well as the presence of aquaporin 4 in the placental tissue, could lead to gestational loss. The aim of this study is to evaluate the influence of the puerperal pregnancy cycle on the course of NMO. METHODS: Interviewed women with gestation after diagnosis of optic neuromyelitis and submitted to questionnaires with data on the disease, such as annualized rate of relapses and EDSS score before, during and after gestation. Gestational complications were also investigated. RESULTS AND DISCUSSION: 19 women with 30 pregnancies. In only 8 pregnancies, there were no relapses up to 1 year postpartum, some associated with the use of immunosuppressants and/or human immunoglobulin in immediate delivery. Annualized relapses rates stood out in the puerperal period, especially in the first 3 months postpartum, in relation to before- pregnancy ARR. It was observed that pregnancy also increased functional disability in these women. Gestational complications such as miscarriage have not been shown to be more frequent in pregnant women with NMO than in the general population.

A systematic literature review on the European, African and Amerindian genetic ancestry components on Brazilian health outcomes.

The variables such as race, skin colour and ethnicity have become intensely discussed in medicine research, as a response to the rising debate over the importance of the ethnic-racial dimension in the scope of health-disease processes. The aim of this study was to identify the European (EUR), African (AFR) and Amerindian (AMR) ancestries on Brazilian health outcomes through a systematic literature review. This study was carried out by searching in three electronic databases, for studies published between 2005 and 2017. A total of 13 papers were eligible. The search identified the following health outcomes: visceral leishmaniosis, malaria, Alzheimer's disease, neuromyelitis optica, multiple sclerosis, prostate cancer, non-syndromic cleft lip/palate, chronic heart failure, sickle cell disease, primary congenital glaucoma, preterm labour, preterm premature rupture of membranes, systemic lupus erythematosus and type 1 diabetes mellitus. Research paper assessments were guided by the STROBE instrument, and agreements between results were determined by comparing the points attributed by two authors. Increased EUR ancestry was identified from preterm labour (PTL), type 1 diabetes (T1D) and non-syndromic cleft lip with or without cleft palate (NSCL), as well as in patients presenting aggressive prostate cancer prognoses. On the other hand, the highest AFR ancestral component was verified from systemic lupus erythematosus (SLE) and primary congenital glaucoma (PCG) cases, presenting worse prognoses. AMR ancestry may be a protective factor in the development of Alzheimer's disease (AD). The worst hemodynamic parameters in cases of heart failure (HF) were identified among individuals with greater AMR and AFR ancestry indices.

Benign multiple sclerosis: aspects of cognition and neuroimaging.

The existence of a benign multiple sclerosis (BMS) form is a controversial subject. Recent studies of these patients reveal different levels of cognitive impairment, despite the apparent preservation of motor function. The objective of this study was to review and analyze a number of publications that discuss the general aspects of this disease form, such as the definition criteria, prevalence, and clinical and neuroimaging markers. A systematic review of published data on BMS up to October 2015 was performed. Thirty-one published articles were analyzed. The estimated frequency of BMS varied between 6% and 73%. Cognitive impairment was recognized as affecting 17% to 47% of the subjects and presented significant correlation with neuroimaging, such as brain atrophy, increased lesion volume in T2 magnetic resonance assay, and regional grey matter atrophy. The current criteria overestimated the frequency of BMS and, for that reason, this highlights the importance of validating the diagnostic methods practiced.

Malignant multiple sclerosis: clinical and demographic prognostic factors.

Patients with malignant multiple sclerosis (MMS) reach a significant level of disability within a short period of time (Expanded Disability Status Scale score of 6 within five years). The clinical profile and progression of the disease were analyzed in a Brazilian cohort of 293 patients. Twenty-five (8,53%) patients were found to have MMS and were compared with the remaining 268 (91,47%). Women, non-white patients, older age at disease onset, shorter intervals between the first attacks, and more attacks in the first two years of the disease were all more common in the MMS group. These findings could serve as prognostic factors when making therapeutic decisions.

Fatigue favors in vitro Th1 and Th17-like cell expansion and reduces corticoid sensitivity in MS patients.

Fatigue is a common "ghost" symptom in patients with multiple sclerosis (MS), an autoimmune disease mediated by T cells that target myelin antigens of the central nervous system. As fatigue has been associated with inflammatory states, its occurrence may negatively impact MS progression. The aim of this study was to evaluate the impact of fatigue on the cytokine profile of patients with relapsing-remitting (RR) MS. For our study, blood were collected from MS patients in clinical remission phase with (n=15) and without (n=15) fatigue. Cytokines were detected by ELISA in the plasma and supernatant collected from anti-CD3/anti-CD28-activated T cells or LPS-stimulated monocytes. In some wells, different doses of hydrocortisone (HC) were added at the beginning of the culture. Here, peripheral levels of IL-6 and TNF-α, as well as in vitro production of cytokines related to Th17 (IL-6, IL-17, IL-22, and GM-CSF) or Th1 (IFN-γ) phenotypes, were elevated in fatigued patients and their levels were associated with fatigue severity. The same phenomenon was observed between the production of IL-6, TNF-α, IL-1ß, and IL-23 by monocytes and fatigue. Moreover, HC was less efficient in inhibiting in vitro inflammatory cytokine production in patients with fatigue, mainly those produced by both CD8+ T cells and monocytes. Our data, although preliminary, suggests that the occurrence of fatigue, by favoring the in vitro production of Th1/Th17-related cytokines and corticoid resistance, may negatively impact the course of MS.

Disability and progression in Afro-descendant patients with multiple sclerosis.

Multiple sclerosis (MS) prevalence is higher in Caucasian (CA) populations, narrowing the analysis of the impact of Afro-descendant (AD) populations in disease outcomes. Even so, recent studies observed that AD patients have a more severe course. The main objective of this study is to confirm and discuss, through a systematic review, that being AD is a risk factor for disability accumulation and/or severe progression in patients with MS. A systematic review of published data in the last eleven years was performed, which evaluated clinical aspects and long term disability in patients with MS. Fourteen studies were included. Of these fourteen articles, thirteen observed a relationship between ancestry and poorer outcome of MS. African ancestry is a condition inherent in the patient and should be considered as an initial clinical characteristic affecting prognosis, and influencing which therapeutic decision to make in initial phases.

Prognostic factors associated with long-term disability and secondary progression in patients with Multiple Sclerosis.

BACKGROUND: Predicting the long-term prognosis of patients with multiple sclerosis (MS) remains an uncertain and difficult task, with most data having been obtained exclusively from Caucasian cohorts. OBJECTIVE: To investigate clinical prognostic factors in a Brazilian mixed-race cohort. METHODS: Demographic, clinical and therapeutic factors were investigated in 303 patients with relapsing-remitting MS in relation to the following outcomes: time until reaching Expanded Disability Status Scale (EDSS) 3 and EDSS 6, and until secondary progression. RESULTS: Benign course was significantly more frequent among Caucasians when compared to Afrodescendants. Patients with a malignant course had more than one relapse in the first year of the disease and reached EDSS 3 faster if treatment was not started. In the multivariate analysis, the following factors were associated with a significantly shorter time until the established outcomes: male gender, being of African descent, non-recovery after the first relapse, two or more relapses during the first year, a short interval between initial relapses, initial polysymptomatic presentation of pyramidal and cerebellar dysfunction and no treatment prior to reaching EDSS 3. CONCLUSIONS: Being of African descent was found to be an unfavorable factor for all outcomes, reinforcing the need to take ethnicity into consideration when defining treatment, particularly in mixed MS populations.

Combined exercise training reduces fatigue and modulates the cytokine profile of T-cells from multiple sclerosis patients in response to neuromediators.

Fatigue is a common and disabling symptom of multiple sclerosis (MS), a classical Th1- and Th17-mediated autoimmune disease. There is no effective pharmacological treatment for fatigue, but some reports point towards beneficial effects of physical activity on management of the fatigue in MS patients. As both MS and fatigue have been associated with dysregulated cytokine network production, the objective of the present study was to evaluate the impact of a physical activity program consisting of a 12-week series of combining Pilates and aerobic exercises on fatigue severity, determined by FSS, and cytokine production, quantified by ELISA, by T cells from MS patients (n=08) with low disability (EDSS≤2). The results showed decrease in FSSs in all patients at the end of physical activity intervention. Regarding the cytokines, a significant reduction of IL-22 release was observed in polyclonally-activated T cells form MS patients post-training follow-up. Interestingly, while the physical activity attenuated the ability of dopamine in up-regulating Th17-related cytokines, it enhanced the anti-inflammatory effects of serotonin, evidenced by high IL-10 production. In summary, all results suggest that programmed physical activity has beneficial effects on management of fatigue in MS patients, and it could be related, at least in part, to its ability in regulating neuroimmune parameters into T cell compartment.

Personality factors in recently diagnosed multiple sclerosis patients: a preliminary investigation with the NEO-FFI scale.

This article describes some prevalent personality dimensions of recently diagnosed multiple sclerosis patients. A sample of 33 female recently diagnosed with relapsing-remitting multiple sclerosis (RRMS) was assessed with the NEO-FFI personality scale. Beck depression (BDI) and anxiety (BAI) scales were also used. No significant levels of anxiety or depression were identified in this group. As for personality factors, conscientiousness was the most common factor found, whereas openness to experience was the least observed. Literature on the relationship between personality and MS is scarce and there are no Brazilian studies on this subject. Some personality traits might complicate or facilitate the experience of living with a chronic, disabling and uncertain neurological condition such as MS.

CLIPPERS syndrome: Case report in a Brazilian patient with a long term disease evolution.

INTRODUCTION: Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids (CLIPPERS Syndrome) was first described in 2010. Since then, about 50 cases have been reported around the world, but none in Portuguese-speaking countries. We report a case of patient of the Neurological Rehabilitation ward of Sarah Hospital/Brasilia, with clinical and radiologic features compatible with CLIPPERS Syndrome. The diagnosis was made only after fourteen years of symptoms onset. CASE REPORT: 49-year-old male, presenting with progressive pancerebellar syndrome followed by spastic paraplegia with neurogenic bladder and progressive worsening over 14 years. The radiological response to steroid was suggestive of CLIPPERS Syndrome, however it was not accompanied by significant clinical improvement. CONCLUSION: This is the first described case in Brazil,and this pattern of progression suggests that CLIPPERS is a degenerative disease. Its relevance must be acknowledged for being an important differential diagnosis of multiple sclerosis and other demyelinating diseases. Early diagnosis may be critical to halt the progression and affect outcome of the disease.

A cluster of transverse myelitis following dengue virus infection in the brazilian Amazon region.

BACKGROUND AND PURPOSE: During the last two decades, clinical reports have begun to place increasing emphasis on the possible neurological complications related to dengue. However, reports of cases with myelitis post dengue are rare. This study describes an unprecedented cluster of transverse myelitis following a dengue virus infection. METHODS: 51 possible cases of neurological complications related to dengue were identified by the epidemiological surveillance of the State of Rondônia, Brazil and submitted to serial neurological examination, electromyography, vertebral MR and laboratory investigation to confirm the dengue diagnosis and rule out other arboviruses. RESULTS: The diagnosis of acute transverse myelitis post-dengue was established in 26 patients, the majority were women, young and white. Antibodies against virus IgM were present in all cases and DEN 3 virus was isolated by PCR in one patient. Treatment with IV steroids was useful. CONCLUSIONS: The cluster of transverse myelitis post-dengue with favorable clinical outcome here reported suggests an immune mediated mechanism for the spinal cord involvement. Whereas dengue epidemics are frequent in tropical and subtropical countries, the dengue fever should be part in the differential diagnosis of the infectious and post-infectious myelitis.

A short neuropsychological evaluation of patients with primary Sjögren's syndrome.

OBJECTIVE: To investigate cognitive deficits in patients with primary Sjögren's syndrome (PSS). METHOD: Eighteen patients with PSS, aged between 25 and 61 years, were subjected to a short neuropsychological battery and compared with 18 patients with multiple sclerosis and 18 healthy controls. RESULTS: The analysis of variance (ANOVA) revealed that the clinical groups had significantly worse performance than the control group on the Rey Auditory Verbal Learning Test 3; (F(2,53) =3.500, p=0.038) and 7 (F(2,53) =5.068, p=0.010). The clinical groups had elevated levels of depression on the Beck Depression Inventory (BDI); (p=0.003). The analysis of the data from the Trail Making Test B-A revealed a significant difference between the clinical and control groups (p=0.023). The analysis of covariance with BDI score as a covariate, did not change the outcome. CONCLUSION: Our study revealed cognitive deficits in patients with PSS detectable by a short neuropsychological battery.