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Expert Opinion on Drug Safety Apr 2020: Immune checkpoint inhibitors (ICI) are associated with a wide spectrum of neurologic immune-related adverse events (irAEs) including meningo-encephalitis, myasthenia... (Review)
Review
: Immune checkpoint inhibitors (ICI) are associated with a wide spectrum of neurologic immune-related adverse events (irAEs) including meningo-encephalitis, myasthenia gravis and various neuropathies. Although relatively rare, they often present significant diagnostic complexity and may be under-recognized. Permanent neurologic deficits and/or fatality have been described but improvement is noted in most cases with ICI discontinuation and immunosuppressive therapy.: This review highlights the most frequently reported ICI-associated neurologic toxicities with a particular focus on those that may be more severe and/or fatal. Data from case series and pharmacovigilance studies is leveraged to provide an overview of associated clinical features, expected outcomes and appropriate management. Various immunobiologic triggers have been proposed to explain why certain patients might develop neurologic irAEs and are also briefly discussed.: All providers who care for patients with cancer should be made aware of common neurologic irAEs and able to recognize when prompt evaluation and consultation with appropriate specialists are indicated. Symptoms suggestive of encephalitis, myasthenia-gravis or an acute polyradiculopathy such as Guillain-Barre Syndrome (GBS) in patients exposed to these agents warrant immediate attention with a low threshold for hospitalization to expedite work-up and monitor for severe and/or life-threatening manifestations.
Topics: Animals; Antineoplastic Agents, Immunological; Humans; Immune Checkpoint Inhibitors; Neoplasms; Neurotoxicity Syndromes
PubMed: 32126176
DOI: 10.1080/14740338.2020.1738382 -
International Orthopaedics Feb 2022International uniformity of definition and classification are crucial for diagnosis and management of cauda equina syndrome (CES). They are also useful for clinicians... (Review)
Review
PURPOSE
International uniformity of definition and classification are crucial for diagnosis and management of cauda equina syndrome (CES). They are also useful for clinicians when discussing CES with patients and relatives, and for medicolegal purposes.
METHODS
We reviewed published literature using PubMed on definition and classification of cauda equina syndrome since 2000 (21 years). Using the search terms 'cauda equina' and 'definition' or 'classification', we found and reviewed 212 papers.
RESULTS
There were 17 different definitions of CES used in the literature. There were three well-defined methods of classification of CES. The two-stage system of incomplete CES (CESI) versus CES with retention (CESR) is the most commonly used classification, and has prognostic value although the details of this continue to be debated.
CONCLUSION
We used the existing literature to propose a clear definition of CES. We also drew on peer-reviewed published literature that has helped to amplify and expand the CESI/CESR dichotomy, adding categories that are both less severe than CESI, and more severe than CESR, and we propose clear definitions in a table form to assist current and future discussion and management of CES.
Topics: Cauda Equina Syndrome; Humans; Polyradiculopathy; Prognosis
PubMed: 34862914
DOI: 10.1007/s00264-021-05273-1 -
Journal of Neurology Apr 2021Since coronavirus disease-2019 (COVID-19) outbreak in January 2020, several pieces of evidence suggested an association between the spectrum of Guillain-Barré...
Since coronavirus disease-2019 (COVID-19) outbreak in January 2020, several pieces of evidence suggested an association between the spectrum of Guillain-Barré syndrome (GBS) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Most findings were reported in the form of case reports or case series, whereas a comprehensive overview is still lacking. We conducted a systematic review and searched for all published cases until July 20th 2020. We included 73 patients reported in 52 publications. A broad age range was affected (mean 55, min 11-max 94 years) with male predominance (68.5%). Most patients showed respiratory and/or systemic symptoms, and developed GBS manifestations after COVID-19. However, asymptomatic cases for COVID-19 were also described. The distributions of clinical variants and electrophysiological subtypes resemble those of classic GBS, with a higher prevalence of the classic sensorimotor form and the acute inflammatory demyelinating polyneuropathy, although rare variants like Miller Fisher syndrome were also reported. Cerebrospinal fluid (CSF) albuminocytological dissociation was present in around 71% cases, and CSF SARS-CoV-2 RNA was absent in all tested cases. More than 70% of patients showed a good prognosis, mostly after treatment with intravenous immunoglobulin. Patients with less favorable outcome were associated with a significantly older age in accordance with previous findings regarding both classic GBS and COVID-19. COVID-19-associated GBS seems to share most features of classic post-infectious GBS and possibly the same immune-mediated pathogenetic mechanisms. Nevertheless, more extensive epidemiological studies are needed to clarify these issues.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; COVID-19; Child; Female; Guillain-Barre Syndrome; Humans; Male; Middle Aged; SARS-CoV-2; Young Adult
PubMed: 32840686
DOI: 10.1007/s00415-020-10124-x -
Journal of Clinical Medicine Nov 2022POEMS is a rare clonal plasma cell disorder characterized by multi-systemic features that include demyelinating peripheral neuropathy, organomegaly, endocrinopathy,... (Review)
Review
POEMS is a rare clonal plasma cell disorder characterized by multi-systemic features that include demyelinating peripheral neuropathy, organomegaly, endocrinopathy, presence of monoclonal proteins (M-protein), and skin changes. Even though the pathophysiology is poorly understood, recent studies suggest that both clonal and polyclonal plasmacytosis leading to the production of pro-inflammatory cytokines and angiogenic mediators play the central role. These mediators including vascular endothelial growth factor (VEGF) are the driving forces of the syndrome. The diagnosis of POEMS is not always straight forward and often the diagnosis is delayed. It is based on fulfilling mandatory criteria of polyradiculoneuropathy and monoclonal protein and the presence of one major criterion (Castleman disease, sclerotic bone lesions, or elevated VEGF), and at least one minor criterion. Due to the presence of neuropathy, it can be confused with chronic inflammatory demyelinating polyradiculopathy (CIDP), and if thrombocytosis and splenomegaly are present, it can be confused with myeloproliferative neoplasms. Due to the rarity of the syndrome, clear guidelines for treatment are still lacking. Immediate treatment targeting the underlying plasma cell proliferation results in a dramatic response in most patients. The key is early diagnosis and immediate anti-plasma cell directed therapy for the best clinical outcomes. For patients with disseminated disease as defined by bone marrow involvement or more than three osteosclerotic bone lesions, high-dose chemotherapy with autologous hematopoietic stem cell transplant (ASCT) yields durable responses and is the preferred treatment in eligible patients. For patients with localized bony disease, radiotherapy has proven to be very effective. Lenalidomide and dexamethasone is a proven therapy in patients ineligible for ASCT. In this review article, we tackle the diagnostic approach and discuss the latest treatment modalities of this rare debilitating disease.
PubMed: 36498588
DOI: 10.3390/jcm11237011 -
World Journal of Oncology Apr 2023Immune checkpoint inhibitors (ICPIs) and chimeric antigen receptor (CAR) T-cell constitute recently approved novel therapies targeted to treat a wide number of... (Review)
Review
Immune checkpoint inhibitors (ICPIs) and chimeric antigen receptor (CAR) T-cell constitute recently approved novel therapies targeted to treat a wide number of malignancies. Both the treatments modulate the immune system and can cause a number of immune-related adverse events (irAEs), including polyendocrinopathies, gastrointestinal and neurological complications. This literature review focuses on the neurological side effects of these therapies as these are uncommon and alter the course of the treatment. Neurological complications involve the peripheral and central nervous system, including polyneuropathy, myositis, myasthenia gravis, demyelinating polyradiculopathy, myelitis, and encephalitis. If early recognized, the neurological complications can be treated effectively with steroids to reduce the potential of short-term and long-term complications. Therefore, early identification and treatment of irAEs are needed to optimize the outcomes associated with ICPI and CAR T-cell therapies.
PubMed: 37188042
DOI: 10.14740/wjon1575 -
The Canadian Journal of Neurological... Jan 2021Albeit primarily a disease of respiratory tract, the 2019 coronavirus infectious disease (COVID-19) has been found to have causal association with a plethora of... (Review)
Review
BACKGROUND
Albeit primarily a disease of respiratory tract, the 2019 coronavirus infectious disease (COVID-19) has been found to have causal association with a plethora of neurological, neuropsychiatric and psychological effects. This review aims to analyze them with a discussion of evolving therapeutic recommendations.
METHODS
PubMed and Google Scholar were searched from 1 January 2020 to 30 May 2020 with the following key terms: "COVID-19", "SARS-CoV-2", "pandemic", "neuro-COVID", "stroke-COVID", "epilepsy-COVID", "COVID-encephalopathy", "SARS-CoV-2-encephalitis", "SARS-CoV-2-rhabdomyolysis", "COVID-demyelinating disease", "neurological manifestations", "psychosocial manifestations", "treatment recommendations", "COVID-19 and therapeutic changes", "psychiatry", "marginalised", "telemedicine", "mental health", "quarantine", "infodemic" and "social media". A few newspaper reports related to COVID-19 and psychosocial impacts have also been added as per context.
RESULTS
Neurological and neuropsychiatric manifestations of COVID-19 are abundant. Clinical features of both central and peripheral nervous system involvement are evident. These have been categorically analyzed briefly with literature support. Most of the psychological effects are secondary to pandemic-associated regulatory, socioeconomic and psychosocial changes.
CONCLUSION
Neurological and neuropsychiatric manifestations of this disease are only beginning to unravel. This demands a wide index of suspicion for prompt diagnosis of SARS-CoV-2 to prevent further complications and mortality.
Topics: Ageusia; Alzheimer Disease; Angiotensin-Converting Enzyme 2; Anosmia; Brain Diseases; COVID-19; Cerebellar Ataxia; Cerebrovascular Disorders; Comorbidity; Delivery of Health Care; Demyelinating Diseases; Disease Management; Dizziness; Epilepsy; Guillain-Barre Syndrome; Headache; Humans; Hypoxia, Brain; Inflammation; Meningoencephalitis; Muscular Diseases; Myelitis, Transverse; Myoclonus; Nervous System Diseases; Parkinson Disease; Polyneuropathies; SARS-CoV-2; Seizures; Stroke; Viral Tropism
PubMed: 32753076
DOI: 10.1017/cjn.2020.173 -
Neurology India 2022Malignant atrophic papulosis (MAP), or systemic Degos disease, is an obliterative vasculopathy of unknown origin, characterized by erythematous papules found on the... (Review)
Review
Malignant atrophic papulosis (MAP), or systemic Degos disease, is an obliterative vasculopathy of unknown origin, characterized by erythematous papules found on the skin, central nervous system (Neuro-MAP) and gastrointestinal tract. Neurological involvement occurs in approximately 20% of systemic cases, is progressive and largely fatal. It can be described in two forms: 1) the parenchymal presenting with meningoencephalitis and meningomyelitis and 2) the neurovascular presenting with large cerebral infarcts, intracranial and subarachnoid hemorrhage, subdural hematoma and venous sinus thrombosis. Predilection to subdural hematoma or hygroma is characteristic for neurological involvement in MAP in comparison to other vasculpathies and vasculitides. Peripheral nervous system manifestations are less common and include polyradiculopathy, neuropathy, and myopathy. CSF analysis usually shows mild to moderate pleocytosis, increased protein content, and normal glucose. Brain MRI may reveal cortical, subcortical and deep white matter ischemic lesions with possible nodular, leptomeningeal, dural, or ependymal enhancement. Spinal cord MRI may reveal patchy lesions from the periphery to the center or cord atrophy in progressive course. Neurological involvement in MAP has a grave prognosis. The interval from onset of papulosis to death averages two years in patients with neurological involvement. There is no confirmed treatment for MAP but there are promising reports with eculizumab and treprostinil.
Topics: Atrophy; Hematoma, Subdural; Humans; Malignant Atrophic Papulosis; Prognosis; Skin
PubMed: 35263846
DOI: 10.4103/0028-3886.338719