Cancers doi: 10.20517/2347-8659.2020.41

Authors: Valeria Mundula, Anna Stainer, Francesca Motta, Michele Ciccarelli

Coronavirus disease-19 (COVID-19) is caused by a severe acute respiratory syndrome coronavirus-2 and was declared a pandemic in March 2020. It mainly causes upper respiratory symptoms, but an interstitial viral pneumonia may occur, in severe cases complicated by acute respiratory distress syndrome. Neurological involvement has been reported but has not been well investigated. A 75-year old man presenting with severe COVID-19 related pneumonia developed a severe cognitive impairment and a right temporal hemianopsia, with focal microangiopathy and subacute ischemic alterations detected on brain imaging, interpreted as vasculitic-inflammatory injury. The neurological disorder was diagnosed only after he was extubated. A rehabilitation program was set up, so the patient had a complete cognitive recovery. Our case underlines how COVID-19 can lead to severe neurological sequelae, so neurological examination should be promptly performed when patients display signs of nervous system involvement, in order to prevent further damages.

Cancers doi: 10.20517/2347-8659.2020.43

Authors: Zahraa I. Khamis, Nancy Al-Akkary, Timothy Hua, Sophia A. Draughon, Yan Li, Qing-Xiang Amy Sang

Human primary brain cancer is one of the most lethal and clinically challenging malignancies. The failure of conventional therapies to alleviate its poor outcome has prompted efforts to find innovative treatments. Recent breakthroughs in immunotherapy across a variety of solid tumors have set immune-based therapeutics as a pillar for brain cancer treatment. However, the unique features of brain malignancies including intratumoral heterogeneity, immunosuppressive microenvironment, and impervious blood-brain barrier, thwart the success of immunotherapeutic approaches. Yet, seminal findings regarding tumor-driven enrichment of specific immune cells granted the field novel insights to harness the immune cells to fight cancer. This review discusses the anatomical, microenvironmental, and immunobiological features of the human brain and presents an overview of immunotherapies tested for primary brain cancer patients with a special emphasis on registered phase 2, 3, and combinatorial clinical trials. Immune checkpoint inhibitors, immune cell-based therapies, cancer vaccines, oncolytic viral therapy, and combination therapies are investigated in clinical settings for the treatment of human brain tumors. Despite their occasional adverse effects, immune-targeted therapies provide a promising opportunity for primary brain cancer patients to enhance survival and improve prognosis.

Cancers doi: 10.20517/2347-8659.2020.47

Authors: Berenice Anabel Silva, Esteban Miglietta, Carina Cintia Ferrari

Multiple sclerosis (MS) is a neurodegenerative and inflammatory disease usually presenting with acute demyelinating events that can start as, or progress to, chronic damage. The development of animal experimental models, specific for each stage of MS will aid in the design of new drugs specific for the different forms of the disease. Animal models of experimental autoimmune encephalomyelitis successfully reflect the pathophysiological mechanisms of the early phases of MS. However, few models resemble the features of the progressive forms of MS such as cortical demyelination and meningeal inflammation. Recently, a few auspicious animal models recapitulating many of the characteristics of progressive MS, aimed at a better understanding of the pathology of these forms of the disease, have been developed. In this review, we will summarize the latest developments in animal models reflecting the cortical and meningeal pathological features of progressive MS, as well as their response to drugs specifically targeting these forms.

Cancers doi: 10.20517/2347-8659.2020.49

Authors: Liesa Regner, Bendix Labeit, Paul Muhle, Tobias Ruck, Rainer Dziewas, Tobias Warnecke, Sonja Suntrup-Krueger

Cranial nerve involvement is rarely seen in chronic inflammatory demyelinating polyneuropathy (CIDP). We present a patient diagnosed with CIDP who was in a stable medical condition under long-term treatment with intravenous immunoglobulin (IVIG) every five weeks for more than seven years. Following a 12-day delay in the patient’s regular IVIG therapy, he developed acute bilateral vocal cord palsy. The patient had to be intubated and tracheostomized because of acute respiratory distress. Weaning from mechanical ventilation was complicated due to pneumonia. After antibiotic treatment and restarting IVIG therapy vocal cord palsy rapidly improved allowing for subsequent decannulation. Although coincidence between treatment delay and symptom development does not prove definitive causality this case report may serve as a reminder how time critical IVIG therapy can be for sufficient symptom control. Moreover, it provides evidence that IVIG therapy may be effective for the treatment of cranial nerve symptoms in CIDP.

Cancers doi: 10.20517/2347-8659.2020.54

Authors: Christian Cordano, Claudia Ramos, Sam Arnow, Andrés Cruz-Herranz, Caroline Guglielmetti, Michele Iester, Fabio Bandini

A provocative and overly reductive mantra is that “the back of the eye is the front of the brain”. Retinal imaging techniques that take advantage of this “window” to the central nervous system can provide valuable information regarding injury to the nervous system with relative ease and with a limited burden to patients. The retina develops embryonically as part of the neuroectoderm, is made up principally of neurons and their supporting cells, and is synaptically tied to the central nervous system (CNS). This has led to significant interest in using retinal health as a biomarker for brain health - given the relatively limited accessibility of brain tissue in chronic neurodegenerative diseases that progress over decades. The retina is not truly part of the CNS, and as with much of brain imaging - the grounds for asserting the pathological specificity of retinal imaging is limited. Biophotonics-based methods such as optical coherence tomography indirectly provide an opportunity to evaluate retinal neurodegeneration, while autopsy studies, histology and immunohistochemistry predominate as the methods that collect direct pathological data. Our understanding of pathological retinal lesions characteristic of demyelinating diseases, specifically diseases showing anterior visual pathway involvement, has grown significantly in recent years. However, much of the underlying pathobiology of injury remain unexplored. This review aims to highlight the major pathological features of the retina in multiple sclerosis, and its most used animal models (experimental autoimmune encephalomyelitis and cuprizone), with a particular focus on n the role of inflammation.

Cancers doi: 10.20517/2347-8659.2020.41

Authors: Valeria Mundula,Anna Stainer,Francesca Motta,Michele Ciccarelli

Coronavirus disease-19 (COVID-19) is caused by a severe acute respiratory syndrome coronavirus-2 and was declared a pandemic in March 2020. It mainly causes upper respiratory symptoms, but an interstitial viral pneumonia may occur, in severe cases complicated by acute respiratory distress syndrome. Neurological involvement has been reported but has not been well investigated. A 75-year old man presenting with severe COVID-19 related pneumonia developed a severe cognitive impairment and a right temporal hemianopsia, with focal microangiopathy and subacute ischemic alterations detected on brain imaging, interpreted as vasculitic-inflammatory injury. The neurological disorder was diagnosed only after he was extubated. A rehabilitation program was set up, so the patient had a complete cognitive recovery. Our case underlines how COVID-19 can lead to severe neurological sequelae, so neurological examination should be promptly performed when patients display signs of nervous system involvement, in order to prevent further damages.

Cancers doi: 10.20517/2347-8659.2020.43

Authors: Zahraa I. Khamis,Nancy Al-Akkary,Timothy Hua,Sophia A. Draughon,Yan Li,Qing-Xiang Amy Sang

Human primary brain cancer is one of the most lethal and clinically challenging malignancies. The failure of conventional therapies to alleviate its poor outcome has prompted efforts to find innovative treatments. Recent breakthroughs in immunotherapy across a variety of solid tumors have set immune-based therapeutics as a pillar for brain cancer treatment. However, the unique features of brain malignancies including intratumoral heterogeneity, immunosuppressive microenvironment, and impervious blood-brain barrier, thwart the success of immunotherapeutic approaches. Yet, seminal findings regarding tumor-driven enrichment of specific immune cells granted the field novel insights to harness the immune cells to fight cancer. This review discusses the anatomical, microenvironmental, and immunobiological features of the human brain and presents an overview of immunotherapies tested for primary brain cancer patients with a special emphasis on registered phase 2, 3, and combinatorial clinical trials. Immune checkpoint inhibitors, immune cell-based therapies, cancer vaccines, oncolytic viral therapy, and combination therapies are investigated in clinical settings for the treatment of human brain tumors. Despite their occasional adverse effects, immune-targeted therapies provide a promising opportunity for primary brain cancer patients to enhance survival and improve prognosis.

Cancers doi: 10.20517/2347-8659.2020.47

Authors: Berenice Anabel Silva,Esteban Miglietta,Carina Cintia Ferrari

Multiple sclerosis (MS) is a neurodegenerative and inflammatory disease usually presenting with acute demyelinating events that can start as, or progress to, chronic damage. The development of animal experimental models, specific for each stage of MS will aid in the design of new drugs specific for the different forms of the disease. Animal models of experimental autoimmune encephalomyelitis successfully reflect the pathophysiological mechanisms of the early phases of MS. However, few models resemble the features of the progressive forms of MS such as cortical demyelination and meningeal inflammation. Recently, a few auspicious animal models recapitulating many of the characteristics of progressive MS, aimed at a better understanding of the pathology of these forms of the disease, have been developed. In this review, we will summarize the latest developments in animal models reflecting the cortical and meningeal pathological features of progressive MS, as well as their response to drugs specifically targeting these forms.

Cancers doi: 10.20517/2347-8659.2020.49

Authors: Liesa Regner,Bendix Labeit,Paul Muhle,Tobias Ruck,Rainer Dziewas,Tobias Warnecke,Sonja Suntrup-Krueger

Cranial nerve involvement is rarely seen in chronic inflammatory demyelinating polyneuropathy (CIDP). We present a patient diagnosed with CIDP who was in a stable medical condition under long-term treatment with intravenous immunoglobulin (IVIG) every five weeks for more than seven years. Following a 12-day delay in the patient’s regular IVIG therapy, he developed acute bilateral vocal cord palsy. The patient had to be intubated and tracheostomized because of acute respiratory distress. Weaning from mechanical ventilation was complicated due to pneumonia. After antibiotic treatment and restarting IVIG therapy vocal cord palsy rapidly improved allowing for subsequent decannulation. Although coincidence between treatment delay and symptom development does not prove definitive causality this case report may serve as a reminder how time critical IVIG therapy can be for sufficient symptom control. Moreover, it provides evidence that IVIG therapy may be effective for the treatment of cranial nerve symptoms in CIDP.

Cancers doi: 10.20517/2347-8659.2020.54

Authors: Christian Cordano,Claudia Ramos,Sam Arnow,Andrés Cruz-Herranz,Caroline Guglielmetti,Michele Iester,Fabio Bandini

A provocative and overly reductive mantra is that “the back of the eye is the front of the brain”. Retinal imaging techniques that take advantage of this “window” to the central nervous system can provide valuable information regarding injury to the nervous system with relative ease and with a limited burden to patients. The retina develops embryonically as part of the neuroectoderm, is made up principally of neurons and their supporting cells, and is synaptically tied to the central nervous system (CNS). This has led to significant interest in using retinal health as a biomarker for brain health - given the relatively limited accessibility of brain tissue in chronic neurodegenerative diseases that progress over decades. The retina is not truly part of the CNS, and as with much of brain imaging - the grounds for asserting the pathological specificity of retinal imaging is limited. Biophotonics-based methods such as optical coherence tomography indirectly provide an opportunity to evaluate retinal neurodegeneration, while autopsy studies, histology and immunohistochemistry predominate as the methods that collect direct pathological data. Our understanding of pathological retinal lesions characteristic of demyelinating diseases, specifically diseases showing anterior visual pathway involvement, has grown significantly in recent years. However, much of the underlying pathobiology of injury remain unexplored. This review aims to highlight the major pathological features of the retina in multiple sclerosis, and its most used animal models (experimental autoimmune encephalomyelitis and cuprizone), with a particular focus on n the role of inflammation.