Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease.

This evidence-based clinical practice guideline for the prevention, diagnosis, and treatment of Lyme disease was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR). The scope of this guideline includes prevention of Lyme disease, and the diagnosis and treatment of Lyme disease presenting as erythema migrans, Lyme disease complicated by neurologic, cardiac, and rheumatologic manifestations, Eurasian manifestations of Lyme disease, and Lyme disease complicated by coinfection with other tick-borne pathogens. This guideline does not include comprehensive recommendations for babesiosis and tick-borne rickettsial infections, which are published in separate guidelines. The target audience for this guideline includes primary care physicians and specialists caring for this condition such as infectious diseases specialists, emergency physicians, internists, pediatricians, family physicians, neurologists, rheumatologists, cardiologists and dermatologists in North America.

Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease.

This evidence-based clinical practice guideline for the prevention, diagnosis, and treatment of Lyme disease was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR). The scope of this guideline includes prevention of Lyme disease, and the diagnosis and treatment of Lyme disease presenting as erythema migrans, Lyme disease complicated by neurologic, cardiac, and rheumatologic manifestations, Eurasian manifestations of Lyme disease, and Lyme disease complicated by coinfection with other tick-borne pathogens. This guideline does not include comprehensive recommendations for babesiosis and tick-borne rickettsial infections, which are published in separate guidelines. The target audience for this guideline includes primary care physicians and specialists caring for this condition such as infectious diseases specialists, emergency physicians, internists, pediatricians, family physicians, neurologists, rheumatologists, cardiologists and dermatologists in North America.

Central Nervous System Infections in Immunocompromised Patients.

PURPOSE OF REVIEW: This article reviews current epidemiologic trends, clinical presentations, and diagnostic strategies for central nervous system (CNS) infections in human immunodeficiency virus-negative (HIV) patients immunocompromised by their underlying disease or by receipt of immunosuppressive or immunomodulating therapies. Three patient groups are considered: (1) cancer patients; (2) hematopoietic or solid organ transplantation recipients; and (3) patients with autoimmune or inflammatory conditions requiring therapies that alter the host immune response. RECENT FINDINGS: Clinical presentations, associated neuroimaging, and cerebrospinal fluid (CSF) abnormalities differ between immunocompromised and immunocompetent patients. Infections can trigger the emergence of neurotropic antibodies or inflammatory conditions due to treatment with cancer immunotherapies. Unbiased metagenomic assays to identify obscure pathogens help clinicians navigate the increasing range of conditions affecting the growing population of patients with altered immunity. Awareness of clinical presentations and disease and drug-specific risks is important for early diagnosis and intervention in these often life-threatening infections and their noninfectious mimes.

Severe Neuroinvasive West Nile Virus in Association With Anti-CD20 Monotherapy for Multiple Sclerosis.

OBJECTIVES: The objective of this study was to report on the development of neuroinvasive West Nile virus (WNV) infection in the context of anti-CD20 monotherapy for multiple sclerosis (MS). METHODS: This is a case series study. RESULTS: In 2021-2022, we observed 4 cases of neuroinvasive WNV infection in our patient population of 2009 patients with MS on ocrelizumab, compared with a total of 46 cases of neuroinvasive WNV infection reported in Pennsylvania and 40 in New Jersey. Odds were 258 times that of the general population (95% confidence interval 97-691), χ2 p < 0.0001). All were women aged 41-61 years with variable disease duration, level of disability, and duration of anti-CD20 therapy. All presented in summer/early fall with fever, headache, and encephalopathy consistent with meningoencephalitis. Three patients had acute cerebellitis. Two had anterior nerve root involvement progressing to quadriparesis, and 1 developed refractory nonconvulsive status epilepticus. All required intubation and experienced significant morbidity. All had CSF pleocytosis. Two patients were WNV IgM positive in both the serum and CSF, 1 patient had positive serum IgM and CSF metagenomic next-generation sequencing (mNGS), while 1 had positive CSF mNGS with negative serum and CSF antibodies. DISCUSSION: Neuroinvasive WNV infection can develop with anti-CD20 monotherapy in the absence of additional immunosuppression. WNV serologies may be negative in the setting of anti-CD20 treatment; in the appropriate clinical context, one should consider direct detection methods such as PCR or mNGS-based testing.

Immune-mediated encephalopathies with an emphasis on paraneoplastic encephalopathies.

Recent identification of syndromes encompassing psychiatric symptoms, seizures, and movement disorders has led to effective treatments for several previously obscure conditions now known to be immune-mediated encephalopathies. In contrast to long-recognized paraneoplastic neurologic syndromes associated with antibodies to intracellular antigens, these more recently described disorders are not always paraneoplastic, are associated with cell surface antibodies, and may respond to immunosuppressive therapies. In this review, the author discusses clinical presentations, differential diagnosis, immunologic evaluation, and therapeutic options for both groups of disorders.

Medical management of patients with brain tumors.

OPINION STATEMENT: Patients with brain tumors require meticulous attention to medical issues resulting from their disease or its therapy. The following specific issues are the ones most frequently arising in the purview of neurologists: (1) Vasogenic edema: Corticosteroids should be used in divided doses in the minimum amount required to control symptoms and should be tapered as quickly as possible. Some patients may require long-term steroid supplementation, and symptoms of adrenal insufficiency should be investigated with 8 AM: cortisol measurement and treated with appropriate repletion. (2) Seizures: Patients with brain tumors should receive antiepileptic drugs only if they have had seizures, and the drugs should be chosen to minimize cognitive effects and interactions with concurrently administered chemotherapy. Levetiracetam is an excellent choice for patients with partial seizures and is available both orally and parenterally. Lamotrigine is another reasonable choice but requires slow titration. (3) Venous thromboembolism: All brain tumor patients should receive perioperative venous thrombosis prophylaxis with compression boots and enoxaparin or dalteparin. Lifelong treatment with low molecular weight heparinoids or warfarin is required for those developing venous thromboembolism. (4) Other problems: Long-term survivors of brain tumors should be monitored indefinitely for cognitive problems, endocrine dysfunction, and development of secondary neoplasms. Modafinil can improve mood and attention impairments.

Neoplastic Myelopathies.

PURPOSE OF REVIEW: This article reviews the current classification system of primary spinal cord tumors and explores evolving diagnostic and therapeutic strategies for both primary tumors and metastatic tumors to various compartments of the spinal cord. RECENT FINDINGS: The 2016 World Health Organization classification system allows for more precise prognostication of and therapy for spinal cord tumors and has identified new entities, such as the diffuse midline glioma, H3 K27M mutant. Whole-exome sequencing reveals that the genetic background of primary glial spinal cord neoplasms differs from that of their intracranial histologic counterparts in ways that can potentially influence therapy. Targeted and immune checkpoint therapies have improved survival for patients with melanoma and lung cancer and have simultaneously produced novel complications by enhancing radiation toxicity in some cases and by facilitating the emergence of novel autoimmune and paraneoplastic syndromes involving the spinal cord, such as neuromyelitis optica spectrum disorder and syndromes associated with anti-Hu and collapsin response mediator protein-5 (CRMP-5) antibodies. These conditions must be distinguished from tumor or infection. Epidural spinal cord compression treatment paradigms have changed with the advent of robotic surgery and advances in radiation therapy. SUMMARY: Neoplastic myelopathies subsume a wide spectrum of pathologies. Neoplastic cord involvement may be primary or secondary and may be approached diagnostically by the particular spinal cord compartment localization. Primary spinal cord tumors account for only 2% to 4% of primary central nervous system tumors, ranging from low-grade glial neoplasms to malignant tumors. Metastatic malignancy to the epidural or leptomeningeal spaces is more common than primary cord tumors. Differential diagnoses arising in the course of evaluation for cord tumors include myelopathies related to radiation or chemotherapy and paraneoplastic syndromes, all of which are sources of significant morbidity. Knowledge of genetic syndromes and the biologic behavior of diverse histologies together with selective application of surgery, radiation, and targeted therapies can facilitate diagnosis, minimize surgical morbidity, and prolong quality of life.

Clinical Practice Guidelines by the Infectious Diseases Society of America, American Academy of Neurology, and American College of Rheumatology: 2020 Guidelines for the Prevention, Diagnosis, and Treatment of Lyme Disease.

This evidence-based clinical practice guideline for the prevention, diagnosis, and treatment of Lyme disease was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR). The scope of this guideline includes prevention of Lyme disease, and the diagnosis and treatment of Lyme disease presenting as erythema migrans, Lyme disease complicated by neurologic, cardiac, and rheumatologic manifestations, Eurasian manifestations of Lyme disease, and Lyme disease complicated by coinfection with other tick-borne pathogens. This guideline does not include comprehensive recommendations for babesiosis and tick-borne rickettsial infections, which are published in separate guidelines. The target audience for this guideline includes primary care physicians and specialists caring for this condition such as infectious diseases specialists, emergency physicians, internists, pediatricians, family physicians, neurologists, rheumatologists, cardiologists and dermatologists in North America.

Central nervous system infections in cancer patients.

With improved treatments, patients with many types of cancer survive longer. However, both the acute adverse effects of more intensive therapies and the risks of chronic immunosuppression have led to a diverse and evolving spectrum of central nervous system (CNS) infections. The presentation and course of CNS infections in cancer patients may be different from those in patients without cancer, complicating and delaying accurate diagnosis. New syndromes related both to the underlying malignancies and to their treatment continue to emerge. Noninfectious disorders such as adverse drug effects, vascular lesions, and radiation effects can mimic CNS infections. The two major clinical presentations of CNS infections are meningoencephalitic syndromes and focal deficits due to mass lesions. The range of pathogens can be narrowed by considering the type of immune deficit present, local nosocomial trends, and the specific vulnerabilities created by the underlying disease and treatment regimen. Patients undergoing neurosurgical procedures and those receiving hematopoietic cell transplants (HCT) account for the majority of cancer patients with CNS infections. Significant recent changes reviewed here include evolving patterns of bacterial meningitis, current treatment recommendations for fungal infections, special infectious risks associated with immunomodulatory therapies, and neuroimaging techniques to distinguish infection from other intracranial processes.

A case series of PD-1 inhibitor-associated paraneoplastic neurologic syndromes.

Immune checkpoint inhibitors (ICIs) are highly efficacious for treating many solid tumor types. Because of their immune-activating mechanism of action, ICIs can trigger various immune-mediated toxicities. We present three cases: i) a woman with anti-Ri brainstem encephalitis; ii) a man with anti-Hu sensory neuronopathy; and iii) a woman with suspected combined anti-Hu and anti-NMDA paraneoplastic syndromes associated with the initiation of the ICIs pembrolizumab and nivolumab. These cases suggest that ICIs can induce both humoral and cell-mediated paraneoplastic neurologic syndromes. Identifying biomarkers that predict risk of developing ICI-associated paraneoplastic syndromes and the development of efficacious treatment strategies for neurologic ICI-toxicities are critical unmet needs.

Central Nervous System Infections Complicating Immunosuppression and Transplantation.

PURPOSE OF REVIEW: This article reviews infections associated with cancer treatments and immunosuppressive/immunomodulatory therapies used in both neoplastic and non-neoplastic conditions, including hematopoietic cell transplantation and solid organ transplantation. It provides a clinical approach to the most commonly affected patient groups based on clinicoanatomic presentation and disease-specific risks resulting from immune deficits and drugs received. RECENT FINDINGS: The clinical presentations, associated neuroimaging findings, and CSF abnormalities of patients with central nervous system infections who are immunocompromised may differ from those of patients with central nervous system infections who are immunocompetent and may be confused with noninfectious processes. Triggering of brain autoimmunity with emergence of neurotropic antibodies has emerged as a recognized parainfectious complication. New unbiased metagenomic assays to identify obscure pathogens help clinicians navigate the increasing range of conditions affecting the growing population of patients with altered immunity. SUMMARY: Despite evidence-based prophylactic regimens and organism-specific antimicrobials, central nervous system infections continue to cause significant morbidity and mortality in an increasing range of patients who are immunocompromised by their conditions and therapies. Multiple new drugs put patients at risk for progressive multifocal leukoencephalopathy, which has numerous imaging and clinical manifestations; patients at risk include those with multiple sclerosis, for whom infection risk is becoming one of the most important factors in therapeutic decision making. Efficient, early diagnosis is essential to improve outcomes in these often-devastating diseases.

Epidemiology, Treatment, and Complications of Central Nervous System Metastases.

PURPOSE OF REVIEW: Neurologic problems resulting from systemic cancer metastases to brain parenchyma, dura, spinal cord, and leptomeninges are among the most common types of consultations addressed by neurologists. With patients surviving longer from systemic cancer, along with the rapidly evolving therapeutic options, the treatment of these devastating complications has become both more effective and more complicated. This article reviews current patterns of metastatic disease and the increasingly nuanced landscape of evolving therapies, their complications, and their impact on quality of survival. RECENT FINDINGS: Targeted therapies with tyrosine kinase inhibitors and immune checkpoint inhibitors and cytotoxic therapies directed at disease-specific chemosensitivity patterns have dramatically improved the prognosis of non-small cell lung cancer, melanoma, and breast cancer, but have led to some novel complications and altered recurrence patterns. Clinical trials suggest the superiority of hippocampal-avoidance radiation fields and the use of stereotactic radiosurgery over whole-brain radiation therapy to minimize long-term cognitive consequences of radiation therapy. Emerging data document tolerable safety when brain radiation is combined with immunotherapy. Chemotherapy can be a first-line treatment for some inoperable brain metastases, eliminating or deferring whole-brain radiation therapy. Stereotactic body radiation therapy is a new technique of radiation used for spinal and epidural metastases that spares spinal cord tissue while ablating tumors. SUMMARY: Metastases to the nervous system remain devastating, but their prognosis and therapies are more heterogeneous than previously appreciated. Neurologists now can offer more personalized prognostic information based on new stratification criteria, can predict drug complications relevant to the nervous system, and can provide critical partnership in the multidisciplinary effort to balance effective longer-term disease control with treatment-related adverse consequences.

Neurologic Complications of Transplantation.

PURPOSE OF REVIEW: This article describes the diagnosis and management of neurologic problems during hematopoietic cell and solid organ transplantation using time elapsed since transplantation as a guide to expected complications, including drug toxicities, infections, strokes, autoimmune phenomena, disease recurrence, and secondary neoplasms. RECENT FINDINGS: Growing clinical experience in the neurology of transplantation has led to appreciation of the diverse clinical and radiographic spectrum of calcineurin inhibitor-related posterior reversible encephalopathy syndrome (PRES) and progressive multifocal leukoencephalopathy. Novel autoimmune phenomena illustrate the delicate balance between adequate immunosuppression and necessary host inflammatory defenses that can lead to organ rejection. The spectrum of infectious complications has changed with the evolution of new conditioning regimens. SUMMARY: Neurologic problems remain an important source of morbidity and mortality, both in the immediate transplantation period and for years after the procedure. As perioperative management has reduced the incidence of acute infections, graft versus host disease, and organ rejection, problems of long-term survivors require neurologic input into multidisciplinary management of chronic neurologic conditions impacting quality of life.

Medical management of patients with brain tumors.

PURPOSE OF REVIEW: This review provides management recommendations for medical and neurologic problems in patients with brain tumors, including vasogenic edema, infections, seizures, prophylaxis and treatment of venous thromboembolism, drug interactions, cognitive and emotional problems, palliative symptom management, and long-term sequelae of brain tumors and their therapy. RECENT FINDINGS: Non-enzyme-inducing antiepileptic drugs are the preferred category of seizure medication for patients with brain tumors, and levetiracetam is emerging as the drug of choice. Select groups of patients, such as those with cortically based hemorrhagic melanoma metastases, may benefit from prophylactic antiepileptic drug use. Antiangiogenic agents can reduce the steroid requirement of patients with vasogenic edema. Patients with brain tumors remain at risk for infections from the perioperative period through many months after treatment, and steroids may mask signs of infection. Few studies have been done on management of common cognitive issues such as short-term memory deficits and fatigue, but memantine may help delay cognitive deficits in patients receiving whole-brain radiation therapy. Palliative care conversations should begin early in the course of treatment. SUMMARY: Meticulous medical management begins at diagnosis of brain tumors and continues through the active treatment course and into either palliative care strategies or management of long-term sequelae of treatment. During the active treatment phase, problems such as vasogenic edema, seizures, and venous thromboembolism predominate, whereas late complications include the continuing risk of infections; sequelae of radiation such as vascular disease, cavernous angiomas, and cognitive decline; and secondary tumors. Attention to symptom palliation is an important part of the neurologist's role throughout the course of a brain tumor patient's illness.

Nervous system infections in patients with cancer.

The diagnostic approach to the patient with cancer with suspected CNS infection depends on an analysis of the patient's immune defect, the time course of development of manifestations of infection, and the type of clinical syndrome with supportive evidence for a specific diagnosis coming from laboratory and neuroradiographic data. Most patients with CNS infections can be grouped into those with signs of meningitis or meningoencephalitis and those with focal mass lesions. A smaller group presents with stroke-like onset. Except for the group with strokes, those with focal deficits usually present in a more indolent fashion, whereas those with meningitis and encephalitis present more acutely [63]. Patients with B-lymphocyte dysfunction are susceptible to encapsulated bacterial pathogens. Patients with T-lymphocyte impairment develop CNS infections that are caused by intracellular pathogens, particularly viruses (HSV, JC, CMV, HHV-6), Nocardia, Aspergillus, and Toxoplasma. Many noninfectious entities, such as drug treatment complications, radiation effects, recurrent tumor, and paraneoplastic syndromes, can mimic CNS infections. Although cryptococcosis, bacterial meningitis, and some viral infections are easily diagnosed from Gram's stain, culture, or PCR, patients with mass lesions may require tissue biopsy to confirm diagnosis. Patients with cancer differ from normal hosts in the distribution of pathogens, and there is a wider range of differential diagnostic issues, both infectious and noninfectious, for the relatively few clinical syndromes that present as potential CNS infections.

Infections of the cerebellum.

Although the cerebellum can be affected by any infection that also involves other parts of the brain parenchyma, cerebrospinal fluid, or nerve roots, a limited range of infections targets cerebellar structures preferentially. Thus, a primarily cerebellar syndrome narrows infectious differential diagnostic considerations. The differential diagnosis of rapidly evolving cerebellar signs suggesting infection includes prescription or illicit drug intoxications or adverse reactions, inflammatory pseudotumor, paraneoplastic processes, and acute postinfectious cerebellitis. This article discusses the diagnosis and differential diagnosis of viral, bacterial, fungal, and prion pathogens affecting the cerebellum in patterns predictable by pace of illness and by involved neuroanatomic structures.

Neurologic complications of infective endocarditis.

OPINION STATEMENT: Symptomatic neurologic complications of IE are frequent, and asymptomatic cerebral embolism diagnosed by magnetic resonance imaging (MRI) occurs in many more patients. Neurologic complications increase mortality and complicate surgical decision-making. The most common neurologic complication is stroke due to septic embolism. Other complications include micro- and macro-abscesses, infectious aneurysms, and more general toxic-metabolic encephalopathies, cerebrospinal fluid (CSF) pleocytosis, and seizures. Neurologic complications influence diagnosis, management, and prognosis. MRI should be obtained in all patients with suspected IE and may identify cerebral abnormalities in many IE patients who do not have neurologic symptoms. MRI sequences should include diffusion weighted imaging (DWI) and gradient echo (GRE) to detect ischemic and hemorrhagic infarction. The detection of clinically silent ischemic or hemorrhagic brain lesions may affect performance or timing of surgery, choice of valve prosthesis, and antimicrobial or anticoagulant therapeutic planning. Neurologists should recommend urgent cerebral angiography in the setting of intracranial hemorrhage so that endovascular treatment of mycotic (infectious) aneurysms can be planned. Patients with large vegetations by echocardiography should be considered for surgery before embolism occurs. They should be referred to centers with extensive surgical experience in debridement of infected tissue and infectious disease expertise in antibiotic choice. Additional indications for surgery to replace the affected valve include heart failure, difficult-to-treat pathogens (such as fungi), elevated left ventricular or atrial pressure due to valvular regurgitation, and perivalvular abscess. Patients with cerebral embolism due to IE should not be anticoagulated. Anticoagulation should be stopped as soon as a diagnosis of IE is suspected, particularly if S. aureus infection is likely. Early surgery is recommended for those with transient ischemic attacks and small infarctions. Neurologists can assist the surgical team by providing neurological preoperative clearance for surgical intervention. Contraindications to early valve replacement include coma, large cerebral infarctions and intracranial hemorrhage.

The spinal cord: a review of functional neuroanatomy.

The spinal cord controls the voluntary muscles of the trunk and limbs and receives sensory input from these areas. It extends from the medulla oblongata to the lower border of the first lumbar vertebra. A basic knowledge of spinal cord anatomy is essential for interpretation of clinical signs and symptoms and for understanding of pathologic processes involving the spinal cord. In this article, anatomic structures are correlated with relevant clinical signs and symptoms and a step-wise approach to spinal cord diagnosis is outlined.