MRI negative myelopathy post mild SARS-CoV-2 infection: vasculopathy or inflammatory myelitis?

Journal of NeuroVirology - Since the onset of the COVID-19 pandemic, there have been rare reports of spinal cord pathology diagnosed as inflammatory myelopathy and suspected spinal cord ischemia...     

Cognitive and behavioral manifestations in SARS-CoV-2 infection: not specific or distinctive features?

Neurological Sciences - Patients with COVID-19 are increasingly reported to suffer from a wide range of neurological complications, affecting both the central and peripheral nervous system. Among...     

Fabry's disease and psychosis: causality or coincidence?

A 21-year-old female with Fabry's disease (FD) presented acute psychotic symptoms such as delusions, auditory hallucinations and formal thought disorders. Since the age of 14, she had suffered from various psychiatric symptoms increasing in frequency and intensity. We considered the differential diagnoses of prodromal symptoms of schizophrenia and organic schizophrenia-like disorder. Routine examinations including cognitive testing, electroencephalography and structural magnetic resonance imaging revealed no pathological findings. Additional structural and functional imaging demonstrated a minor CNS involvement of FD, yet without functional limitations. In summary our examination results support the thesis that in the case of our patient a mere coincidence of FD and psychotic symptoms is more likely than a causal connection.     

Neural activation during an explicit categorization task: category- or feature-specific effects?

Previous lesion-deficit and functional imaging studies have suggested that there are distinct category-specific regions within the human brain. Using functional magnetic resonance imaging, we tested this claim with a task in which participants decided if two items, represented by words, were members of the same category. Signal changes detected for all pairs of items that were from the same category and for tool pairs were found in rostromedial BA 6, rostral cingulate, and at the BA 6/44 and BA 45/46 junctions. Activation was seen in BA 6 and the left BA 6/44 junction for fruits and vegetables pairs and only in rostromedial BA 6 for animal pairs. The common signal changes in the frontal lobes (BA 6/44) for the categories of fruits and vegetables and tools suggest that this region may be organized in a feature-specific, as opposed to a category-specific, manner.     

Malignant melanoma and levodopa in Parkinson's disease: causality or coincidence?

Levodopa is the major drug used in the treatment of patients with Parkinson's disease. However, levodopa continues to be ‘contra-indicated’ for patients with Parkinson's disease associated with malignant melanoma. Case reports have suggested that levodopa has a causal relationship with malignant melanoma due to their shared dopamine biochemical pathway. Clinical characteristics of 54 patients with both Parkinson's disease and melanoma were analyzed (43 cases from the literature and 11 from our institution). The results suggest that the occurrence of both Parkinson's disease and melanoma in these patients is coincidental rather than causal. It did not appear that the Parkinson's disease patients on levodopa therapy were predisposed to melanoma, nor did levodopa therapy appear to exaggerate melanoma if it were previously present.     

Neurobiology of placebo effects: expectations or learning?

Contemporary learning theories suggest that conditioning is heavily dependent on the processing of prediction errors, which signal a discrepancy between expected and observed outcomes. This line of research provides a framework through which classical theories of placebo effects, expectations and conditioning, can be reconciled. Brain regions related to prediction error processing [anterior cingulate cortex (ACC), orbitofrontal cortex or the nucleus accumbens] overlap with those involved in placebo effects. Here we examined the possibility that the magnitude of objective neurochemical responses to placebo administration would depend on individual expectation-effectiveness comparisons. We show that such comparisons and not expectations per se predict behavioral placebo responses and placebo-induced activation of µ-opioid receptor-mediated neurotransmission in regions relevant to error detection (e.g. ACC). Expectations on the other hand were associated with greater µ-opioid system activation in the dorsolateral prefrontal cortex but not with greater behavioral placebo responses. The results presented aid the elucidation of molecular and neural mechanisms underlying the relationship between expectation-effectiveness associations and the formation of placebo responses, shedding light on the individual differences in learning and decision making. Expectation and outcome comparisons emerge as a cognitive mechanism that beyond reward associations appears to facilitate the formation and sustainability of placebo responses.     

Neurosarcoidosis Flare with Multifocal Restricted Diffusion: Stroke,Inflammation, or Both?

Sarcoidosis is a multisystem granulomatous disease that can cause a wide range of neurologic symptoms. Leptomeningeal enhancement is frequently described but reports of stroke-like symptoms or the appearance of ischemia on magnetic resonance imaging are rare. We present a case of a patient with both leptomeningeal enhancement and multifocal restricted diffusion in a patient with sarcoidosis.     

Clinically definite ALS presenting weeks after mild electric injury: causality or coincidence?

Motor neuron syndromes including typical ALS develop very rarely after electrotrauma, with possible causality discussed but not confirmed. We report on a 44-year-old male who developed clinically definite ALS by the revised El Escorial criteria with onset weeks after mild electric injury. He presented with asymmetric upper limb amyotrophy and weakness beginning around the entry point of the current. Over 1?year he developed generalized wasting, weakness and fasciculations, including the bulbar and thoracic muscles, with prominent spasticity and pyramidal tract signs. Electrodiagnostic studies confirmed widespread denervation, very unstable neurogenic motor units in the bulbar, cervical, thoracic and lumbosacral segments with normal motor velocities and normal sensory parameters. This is a well-documented case of fast-progressive ALS that seems related to electric injury.     

Blood-brain barrier breakdown during cerebral malaria: suicide or murder?

Cerebral malaria, one of the most serious complications of Plasmodium falciparum infection, is characterized by the sequestration of parasitized red blood cells (PRBCs) in cerebral microvascular beds. The precise mechanisms involved in the onset of neuropathology remain unknown, but parasite sequestration in the brain, metabolic disturbances, and host immune responses all play a role. Sequestration of PRBCs is mediated by different endothelial cell surface receptors, mainly ICAM-1 and CD36. In vitro studies demonstrated that PRBC adhesion to endothelial cells induces over-expression of various adhesion molecules including ICAM-1, expression of iNOS, oxidative stress and finally apoptosis in endothelial cells. In vivo studies, in humans and in mice models of cerebral malaria brought striking evidence of the implication of brain infiltrating cytotoxic effector CD8T lymphocytes in the development of murine cerebral malaria pathogenesis. These cells probably act by direct cytotoxicity against endothelial cells. Cytotoxicity and apoptosis potentially lead blood-brain-barrier disruption and could contribute to the development of cerebral malaria. We propose a key role for endothelial cells in the pathogenesis of cerebral malaria, both by suicide / apoptosis, and / or by murder / cytotoxicity.     

Cytoskeletal abnormalities in amyotrophic lateral sclerosis: beneficial or detrimental effects?

Cytoskeletal abnormalities have been reported in cases of amyotrophic lateral sclerosis (ALS) including abnormal inclusions containing neurofilaments (NFs) and/or peripherin, reduced mRNA levels for the NF light (NF-L) protein and mutations in the NF heavy (NF-H) gene. Recently, transgenic mouse approaches have been used to address whether cytoskeletal changes may contribute to motor neuron disease. Mice lacking one of the three NF subunits are viable and do not develop motor neuron disease. Nonetheless, mice with null mutations for NF-L or for both NF-M and NF-H genes developed severe atrophy of ventral and dorsal root axons. The atrophic process is associated with hind limb paralysis during aging in mice deficient for both NF-M and NF-H proteins. The overexpression in mice of transgenes coding for wild-type or mutant NF proteins can provoke abnormal NF accumulations, axonal atrophy and sometimes motor dysfunction. However, the perikaryal NF accumulations are generally well tolerated by motor neurons and, except for expression of a mutant NF-L transgene, they did not provoke massive motor neuron death. Increasing the levels of perikaryal NF proteins may even confer protection in motor neuron disease caused by ALS-linked mutations in the superoxide dismutase (SOD1). In contrast, the overexpression of wild-type peripherin, a type of IF gene upregulated by inflammatory cytokines, provoked the formation of toxic IF inclusions with the high-molecular-weight NF proteins resulting in the death of motor neurons during aging. These results together with the detection of peripherin inclusions at early stage of disease in mice expressing mutant SOD1 suggest that IF inclusions containing peripherin may play a contributory role in ALS pathogenesis.     

Guillain–Barré syndrome as a parainfectious manifestation of SARS-CoV-2 infection: A case series

The global SARS-CoV-2 pandemic posed an unprecedented challenge to almost all fields of medicine and Neurology is not an exception. Collecting information about its complications and related conditions will help clinicians to become more confident in managing this disease. Guillain-Barre Syndrome (GBS) is mostly described as a post-infectious phenomenon and its occurrence during acute phase of illness is of interest. GBS has recently been reported during the active phase of COVID-19 for the first time. Severity and fast progression of GBS associated with COVID-19 have also been shown in recent studies. Here we report three cases of GBS during the active phase of COVID-19 with severe symptoms and fast progression to quadriplegia and facial diplegia over 2 days, which led to death in one case due to severe autonomic dysfunction. We suggest SARS-CoV-2 might be associated with rather a severe, rapidly progressive and life-threatening phenotype of GBS.     

Fate of microglia during HIV‐1 infection: From activation to senescence?

Microglia support productive human immunodeficiency virus type 1 (HIV‐1) infection and disturbed microglial function could contribute to the development of HIV‐associated neurocognitive disorders (HAND). Better understanding of how HIV‐1 infection and viral protein exposure modulate microglial function during the course of infection could lead to the identification of novel therapeutic targets for both the eradication of HIV‐1 reservoir and treatment of neurocognitive deficits. This review first describes microglial origins and function in the normal central nervous system (CNS), and the changes that occur during aging. We then critically discuss how HIV‐1 infection and exposure to viral proteins such as Tat and gp120 affect various aspects of microglial homeostasis including activation, cellular metabolism and cell cycle regulation, through pathways implicated in cellular stress responses including p38 mitogen‐activated protein kinase (MAPK) and nuclear factor κB (NF‐κB). We thus propose that the functions of human microglia evolve during both healthy and pathological aging. Aging‐associated dysfunction of microglia comprises phenotypes resembling cellular senescence, which could contribute to cognitive impairments observed in various neurodegenerative diseases. In addition, microglia seems to develop characteristics that could be related to cellular senescence post‐HIV‐1 infection and after exposure to HIV‐1 viral proteins. However, despite its potential role as a component of HAND and likely other neurocognitive disorders, microglia senescence has not been well characterized and should be the focus of future studies, which could have high translational relevance. GLIA 2017;65:431–446     

Social networks and immunosuppression during stress: relationship conflict or energy conservation?

Despite the apparent health benefits of social relationships, some studies indicate that larger social networks can be associated with greater vulnerability to infectious disease, particularly if stressors are also present. Two possibilities for such effects are, first, that more social contacts lead to more negative affect and social conflict during stressors, or second, that maintaining more social contacts is an energetically costly activity, and ecologically motivated immunosuppression is one means of providing energy to maintain social resources. First-year law students (N=76) completed questionnaires and had delayed-type hypersensitivity skin tests at five time points during their first 6 months of law school. Both moving away from home and a smaller social network associated with larger DTH responses (both p<0.05) across all time points. However, negative affect, either broadly defined or as specific affects (hostility, sadness, guilt), did not mediate social network effects, suggesting that negative affect and social conflict are less plausible explanations than ecological immunosuppression. Ecological models would predict that temporary immunosuppression is less harmful to health in the long run than loss of social resources.     

Long-term biobehavioral effects of maternal separation in the rat: consistent or confusing?

Over the last decades of research there has been increasing interest in endocrine and behavioral effects of postnatal environmental manipulations. A manipulation procedure that has been widely used to date is that of maternal separation. Many studies have demonstrated that, in the rat, a single or repeated separation of the pups from the mother leads to acute as well as long-term effects on endocrinology and behavior. However, reviewing the literature shows that contrary findings for almost all parameters investigated can be found. A possible explanation for this inconsistency may be the fact that maternal separation has become a collective term for a variety of extremely different experimental manipulations. Therefore, this review aims at evaluating typical effects of maternal separation in the laboratory rat by categorizing different experimental procedures. We concentrate in particular on longterm behavioral effects, although a brief summary of neuroendocrine effects is also provided. In addition, important methodological issues of maternal separation studies are discussed as a possible source for inconsistent findings.     

A dynamic causal modeling study on category effects: bottom-up or top-down mediation?

In this study, we combined functional magnetic resonance imaging (fMRI) and dynamic causal modeling (DCM) to investigate whether object category effects in the occipital anti temporal cortex are mediated by inputs from early visual cortex or parietal regions. Resolving this issue may provide anatomical constraints on theories of category specificity--which make different assumptions about the underlying neurophysiology. The data were acquired by Ishai, Ungerleider, Martin, Schouten, and Haxby (1999, 2000) and provided by the National fiNRI Data Center (http://www.fmridcc.org). The original authors used a conventional analysis to estimate differential effects in the occipital anti temporal cortex in response to pictures of chairs, faces, and houses. We extended this approach by estimating neuronal interactions that mediate category effects using DCM. DCM uses a Bayesian framework to estimate and make inferences about the influence that one region exerts over another and how this is affected by experimental changes. DCM differs from previous approaches to brain connectivity, such as multivariate autoregressive models and structural equation modeling, as it assumes that the observed hemodynamic responses are driven by experimental changes rather than endogenous noise. DCM therefore brings the analysis of brain connectivity much closer to the analysis of regionally specific effects usually applied to functional imaging data. We used DCM to estimate the influence that V3 and the superior/inferior parietal cortex exerted over category-responsive regions and how this was affected by the presentation of houses, faces, and chairs. We found that category effects in occipital and temporal cortex were mediated by inputs from early visual cortex. In contrast,the connectivity from the superior/inferior parietal area to the category-responsive areas was unaffected by the presentation of chairs, faces, or houses. These findings indicate that category effects in the occipital and temporal cortex can be mediated by bottom-up mechanisms-a finding that needs to be embraced by models of category specificity.