Magnetic resonance imaging features of COVID-19-related cranial nerve lesions.

The complete features of the neurological complications of coronavirus disease 2019 (COVID-19) still need to be elucidated, including associated cranial nerve involvement. In the present study we describe cranial nerve lesions seen in magnetic resonance imaging (MRI) of six cases of confirmed COVID-19, involving the olfactory bulb, optic nerve, abducens nerve, and facial nerve. Cranial nerve involvement was associated with COVID-19, but whether by direct viral invasion or autoimmunity needs to be clarified. The development of neurological symptoms after initial respiratory symptoms and the absence of the virus in the cerebrospinal fluid (CSF) suggest the possibility of autoimmunity.

Neurological implications of SARS-CoV-2 infection: review of literature / Implicações neurológicas da infecção por SARS-CoV-2: revisão da literatura

The infection caused by the new coronavirus had its first case described in December 2019, in Wuhan, China, and reached a pandemic status in March 2020. Since then, knowledge about the different aspects of this infection has evolved, as well as increased reports concerning related neurological manifestations. Thus, the neurologist assumes a fundamental role in the care of these patients, who may have a clinical phenotype that goes beyond respiratory aspects. In the present study, we highlight the data available in the literature so far regarding the main neurological implications related to COVID-19 infection, in addition to calling attention for some aspects related to patients with previous neurological diseases who contract this infection.

A infecção causada pelo novo Coronavírus teve seu primeiro caso descrito em dezembro de 2019, em Wuhan, China e alcançou o status de pandemia em março de 2020. Desde então, o conhecimento sobre os diferentes aspectos da referida infecção evolui assim como aumentam relatos de manifestações neurológicas relacionadas. Assim, o neurologista assume papel fundamental na assistência desses pacientes, que podem ter um fenótipo clínico que ultrapassa os aspectos respiratórios. No presente estudo, destacamos os dados disponíveis na literatura até o presente momento no tocante às principais implicações neurológicas relacionadas à infecção pelo COVID-19, além de destacar alguns aspectos relativos aos pacientes com doenças neurológicas prévias que contraem a referida infecção.

Applying an artificial neural network model for developing a severity score for patients with hereditary amyloid polyneuropathy.

Hereditary (familial) amyloid polyneuropathy (FAP) is a systemic disease that includes a sensorimotor polyneuropathy related to transthyretin (TTR) mutations. So far, a scale designed to classify the severity of this disease has not yet been validated. This work proposes the implementation of an artificial neural network (ANN) in order to develop a severity scale for monitoring the disease progression in FAP patients. In order to achieve this goal, relevant symptoms and laboratory findings were collected from 98 Brazilian patients included in THAOS - the Transthyretin Amyloidosis Outcomes Survey. Ninety-three percent of them bore Val30Met, the most prevalent variant of TTR worldwide; 63 were symptomatic and 35 were asymptomatic. These data were numerically codified for the purpose of constructing a Self-Organizing Map (SOM), which maps data onto a grid of artificial neurons. Mapped data could be clustered by similarity into five groups, based on increasing FAP severity (from Groups 1 to 5). Most symptoms were virtually absent from patients who mapped to Group 1, which also includes the asymptomatic patients. Group 2 encompasses the patients bearing symptoms considered to be initial markers of FAP, such as first signs of walking disabilities and lack of sensitivity to temperature and pain. Interestingly, the patients with cardiac symptoms, which also carry cardiac-associated mutations of the TTR gene (such as Val112Ile and Ala19Asp), were concentrated in Group 3. Symptoms such as urinary and fecal incontinence and diarrhea characterized particularly Groups 4 and 5. Renal impairment was found almost exclusively in Group 5. Model validation was accomplished by considering the symptoms from a sample with 48 additional Brazilian patients. The severity scores proposed here not only identify the current stage of a patient's disease but also offer to the physician an easy-to-read, 2D map that makes it possible to track disease progression.

Structure-based analysis of A19D, a variant of transthyretin involved in familial amyloid cardiomyopathy.

Transthyretin (TTR) is a tetrameric beta-sheet-rich protein. Its deposits have been implicated in four different amyloid diseases. Although aggregation of the wild-type sequence is responsible for the senile form of the disease, more than one hundred variants have been described thus far, most of which confer a more amyloidogenic character to TTR, mainly because they compromise the stability of the protein in relation to monomer formation, which upon misfolding is intrinsically aggregation-prone. We report the case of a Brazilian patient suffering from a severe cardiomyopathy who carries a rare mutation in exon 2 of the TTR gene that results in an Ala to Asp substitution at position 19 (A19D). The putative pathogenic mechanisms of this variant were analyzed in silico. We constructed a structural model for the A19D tetramer from which its thermodynamic stability was compared to that displayed by the V30M (more amyloidogenic than WT-TTR) and T119M (non-amyloidogenic) variants. The FoldX force field predicted that A19D and V30M are 10.88 and 8.07 kCal/mol less stable than the WT-TTR, while T119M is 5.15 kCal/mol more stable, which is consistent with the aggregation propensities exhibited by these variants. We analyzed the step in which the tetramer-dimer-monomer-unfolded monomer equilibrium might contribute the most to the increased or decreased amyloidogenicity in each variant. Our results suggest that the concentration of four non-native negative charges occur inside thyroxine-binding channels, and the loss of contacts at both the tetrameric and dimeric interfaces would account for an overall decreased stability of the tetramer and the consequent enhanced amyloidogenicity of the A19D variant. As far as we know, this is the first description of a non-V30M mutation in Brazil.