Immune-Mediated Myelopathies: A Review of Etiologies, Diagnostic Approach, and Therapeutic Management.

Myelopathy is a broad term used to describe a heterogeneous group of disorders that affects the spinal cord; the focus of this article will be a subgroup of these disorders with an autoimmune and inflammatory-based pathology. Symptoms typically develop over hours or days and then worsen over a matter of days to weeks, but sometimes can have a more insidious or subacute presentation, which can make the diagnosis more puzzling. Despite relatively low incidence rates, almost a third of affected patients are left with severely disabling symptoms. Prompt recognition of the underlying etiology is essential so that a specific targeted therapy can be implemented for optimal outcomes. The authors discuss a systematic approach to immune-mediated myelopathies, with a focus on the unique characteristics of each that may aid in diagnosis.

Diagnostic Testing in Central Nervous System Infection.

Patients with central nervous system (CNS) infection experience very high levels of morbidity and mortality, in part because of the many challenges inherent to the diagnosis of CNS infection and identification of a causative pathogen. The clinical presentation of CNS infection is nonspecific, so clinicians must often order and interpret many diagnostic tests in parallel. This can be a daunting task given the large number of potential pathogens and the availability of different testing modalities. Here, we review traditional diagnostic techniques including Gram stain and culture, serology, and polymerase chain reaction (PCR). We highlight which of these are recommended for the pathogens most commonly tested among U.S. patients with suspected CNS infection. Finally, we describe the newer broad-range diagnostic approaches, multiplex PCR and metagenomic sequencing, which are increasingly used in clinical practice.

Bedside Teaching in Neurology.

The patient's bedside offers an ideal venue for teaching the art of clinical neurology and modeling humanism and professionalism. However, bedside teaching is underutilized in modern medical education, despite evidence that learners desire more. Logistical challenges and lack of teacher confidence are commonly cited reasons, but both can be mitigated with a deliberate approach and sufficient experience. Well-executed bedside teaching can provide lasting lessons for learners while enhancing the patient experience, without affecting the efficiency or quality care delivery. In this review, we discuss the theory and evidence to support the use of bedside teaching, and subsequently delineate a framework for designing and executing effective bedside teaching in neurology.

The Clinical Approach to Encephalitis.

Encephalitis has various etiologies, but viral infections and autoimmune disorders are the most commonly identified. Clinical signs, geographical clues, and diagnostic testing-including cerebrospinal fluid abnormalities and magnetic resonance imaging abnormalities-can be helpful in identifying the cause. Certain forms of encephalitis have specific treatments; hence, establishing a diagnosis rapidly and accurately is crucial. Here, we describe the clinical approach to diagnosing several common etiologies of encephalitis as well as treatment strategies.

Clinical approach to neurorheumatology.

Rheumatologic conditions are an important cause of both central and peripheral nervous system pathology. A thorough evaluation for an underlying rheumatologic process is an important component of a patient presenting with neurologic symptoms. In this review, the authors present an approach to evaluating rheumatologic conditions, focusing primarily on the history and physical examination. They focus on the most specific signs and symptoms that may help the neurologist assess whether an underlying rheumatologic process is present. In addition, they discuss the interpretation of such findings with an eye toward narrowing the differential diagnosis and directing further testing.

Neurosarcoidosis.

Sarcoidosis is an idiopathic multisystem granulomatous disorder. Neurologic manifestations in sarcoidosis are varied and making a diagnosis of neurosarcoidosis can be difficult as it mimics various other neurologic diseases. Knowledge of the syndromes associated with neurosarcoidosis can help guide the diagnostic evaluation. Definitive diagnosis requires neurologic tissue evidence of noncaseating granuloma, but in practice probable diagnosis is often made through nonneurologic biopsy and a characteristic syndrome and imaging. Treatment remains empiric, but new advances in immunologic therapy hold promise for effective and less-toxic regimens.

A neurologist's guide to safe use of immunomodulatory therapies.

Increased understanding of the pathogenesis of immune-mediated neurologic conditions with concomitant development of new therapeutic agents modulating various aspects of the immune system has resulted in the use of innovative therapies in the treatment of these diseases. These novel immunomodulatory therapeutic regimens also augment the potential for complications, including severe adverse effects.In this review, the authors address practical issues regarding management of patients with neuroimmunological conditions treated with immunomodulatory therapies, including glucocorticoids, methotrexate, azathioprine, mycophenolate, cyclophosphamide, rituximab, tumor necrosis factor-α inhibitors, and intravenous immunoglobulins. Particular focus is placed on their infectious and noninfectious adverse effects, contraindications, safety monitoring, risk surveillance, and preventive strategies in clinical practice.

Pathophysiological mechanisms of headache in patients with HIV.

BACKGROUND: The pathophysiology of human immunodeficiency virus (HIV) is complex. The etiology of headache in the HIV population is often multifactorial, and attributing causality to specific pathophysiological mechanisms is challenging. Headaches can occur any time during the infection and may be primary (as in non-HIV-infected patients) or secondary (either from HIV directly or due to opportunistic disease). DISCUSSION: Direct HIV related headaches are due to the underlying viral pathophysiology. For example, acute meningitis can be seen during HIV-1 seroconversion. Headaches can occur during symptomatic HIV and also after an AIDS-defining illness. Late-stage HIV headache can occur without any pleocytosis. A correlation between viral load and neurological symptoms including headache has been suggested. There may be similar mechanisms involving migraine, tension-type headache, and HIV infection. CONCLUSION: Secondary HIV headaches can be related to opportunistic infections, malignancy, medications used to treat HIV, and immune restoration inflammatory syndrome.

Clinical aspects of headache in HIV.

BACKGROUND: Headaches are commonly seen in those patients with human immunodeficiency virus (HIV) and are the most common form of pain reported among HIV patients. There have been relatively few studies attempting to determine the rates and phenotypes of the headaches that occur in patients with HIV. DISCUSSION: Patients with HIV are susceptible to a much broader array of secondary headache causes, sometimes with atypical manifestations due to a dampened inflammatory response. The investigation of a headache in the HIV patient should be thorough and focused on making sure that secondary and HIV-specific causes are either ruled out or treated if present. CONCLUSION: An effective treatment plan should incorporate the use of appropriate pharmacological agents along with the integration of non-pharmacological therapies, such as relaxation and lifestyle regulation. When treating for headaches in patients with HIV, it is important to keep in mind comorbidities and other medications, especially combination antiretroviral therapy. For those with complicated headache histories, referral to a specialized headache center may be appropriate.

Imaging of Central Nervous System Autoimmune, Paraneoplastic, and Neuro-rheumatologic Disorders.

OBJECTIVE: This article provides an overview of the imaging modalities used in the evaluation of central nervous system (CNS) autoimmune, paraneoplastic, and neuro-rheumatologic disorders. An approach is outlined for interpreting imaging findings in this context, synthesizing a differential diagnosis based on certain imaging patterns, and choosing further imaging for specific diseases. LATEST DEVELOPMENTS: The rapid discovery of new neuronal and glial autoantibodies has revolutionized the autoimmune neurology field and has elucidated imaging patterns characteristic of certain antibody-associated diseases. Many CNS inflammatory diseases, however, lack a definitive biomarker. Clinicians should recognize neuroimaging patterns suggestive of inflammatory disorders, as well as the limitations of imaging. CT, MRI, and positron emission tomography (PET) modalities all play a role in diagnosing autoimmune, paraneoplastic, and neuro-rheumatologic disorders. Additional imaging modalities such as conventional angiography and ultrasonography can be helpful for further evaluation in select situations. ESSENTIAL POINTS: Knowledge of imaging modalities, both structural and functional, is critical in identifying CNS inflammatory diseases quickly and can help avoid invasive testing such as brain biopsy in certain clinical scenarios. Recognizing imaging patterns suggestive of CNS inflammatory diseases can also facilitate the early initiation of appropriate treatments to diminish morbidity and future disability.

Neurologic Complications of COVID-19.

OBJECTIVE: This article describes the spectrum of neurologic complications occurring in acute or postacute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as the neurologic risks and benefits of vaccination against SARS-CoV-2. LATEST DEVELOPMENTS: Early in the COVID-19 pandemic, reports of neurologic complications of COVID-19 began to surface. A variety of neurologic conditions have since been reported in association with COVID-19. Understanding of the underlying mechanism of COVID-19 neurologic involvement continues to evolve; however, the evidence seems to suggest that aberrant inflammatory responses may play a role. In addition to neurologic symptoms in acute COVID-19, neurologic post-COVID-19 conditions are increasingly recognized. The development of COVID-19 vaccines has been essential in preventing the spread of COVID-19. With increasing numbers of vaccine doses administered, various neurologic adverse events have been reported. ESSENTIAL POINTS: Neurologists must be aware of the potential acute, postacute, and vaccine-associated neurologic complications associated with COVID-19 and be poised to serve as integral members of multidisciplinary care teams for patients with COVID-19-related conditions.

Palato-Pharyngo-Laryngeal Rhythmic Myoclonus in Neuro-Behcet Syndrome: A Case Report.

OBJECTIVE: Behcet's syndrome (BS) is a chronic, relapsing multisystemic inflammatory perivasculitis and can affect any tissue, including the nervous system. Neuro-Behcet's syndrome (NBS) most commonly affects the CNS parenchyma and presents with a subacute brainstem syndrome that includes cranial neuropathies. Here we describe a rare case of palato-pharyngo-laryngeal myoclonus as a manifestation of NBS and discuss it from a laryngology perspective. METHODS: Case report at tertiary care center. Informed consent was obtained from patient. IRB approved as non-human subjects research. RESULTS: A 52-year-old male presented with a progressive history of ataxia, fatigue, apathy, dysphagia, depressed mood, dizziness, poor appetite, subjective fever and recurrent orogenital lesions. He was diagnosed with NBS and treated with methylprednisolone, followed by infliximab and methotrexate. Despite treatment, his severe spastic dysarthria, dysphagia, and aspiration worsened over the next few months, necessitating a gastrotomy tube. With concern for laryngospasm, he was referred to otolaryngology and found to have synchronous and symmetric palatal, pharyngeal, and laryngeal rhythmic myoclonus bilaterally at a frequency of 2 Hz with inappropriate vocal cord closure. Treatment with baclofen and a scopolamine patch improved his breathing and reduced choking events. CONCLUSIONS: Palato-pharyngo-laryngeal rhythmic myoclonus can be a presentation of brainstem NBS in the otolaryngology clinic. We theorize perivascular disease in NBS results in a brainstem lesion in the denato-rubro-olivary tract, which results in hypertrophic olivary degeneration and subsequent activation of the inferior olives oscillatory activity, causing palato-pharyngo-laryngeal rhythmic myoclonus. Common symptoms include significant dysarthria, dysphonia, and dysphagia with concern for obstructive sleep apnea and airway compromise. Treatments include pharmacologic therapy, laryngeal botox, and tracheostomy in cases of significant airway compromise.

Atypical nervous system manifestations of HIV.

Despite the widespread success of combination antiretroviral therapy (cART) in reducing morbidity and mortality in human immunodeficiency virus 1 (HIV-1) infection, HIV-associated neurologic disease remains prevalent. Although the virus is unable to infect neurons or muscle fibers directly, it can still injure these structures by a variety of mechanisms, many of which are yet to be elucidated. Additionally, antiretroviral medications used to treat HIV infection can cause damage to the nervous system both by direct toxicity and via modulation of host-virus interactions. Some neurologic complications of HIV infection are rarely seen and are poorly understood; nevertheless, they are important to recognize. In this review article, the authors focus on the uncommon neurologic manifestations of HIV infection, including mononeuropathies, inflammatory demyelinating polyneuropathies, motor neuron disease, polymyositis, diffuse infiltrative lymphocytosis syndrome, mononeuritis multiplex, HIV-associated neuromuscular weakness syndrome, immune reconstitution inflammatory syndrome, and central nervous system HIV-escape meningoencephalomyelitis and myelitis.

Role of infection and neurologic dysfunction in chronic fatigue syndrome.

Chronic fatiguing illnesses following well-documented infections and acute "infectious-like" illnesses of uncertain cause have been reported for many decades. Chronic fatigue syndrome (CFS) was first formally defined in 1988. There is considerable evidence that CFS is associated with abnormalities of the central and autonomic nervous systems. There also is evidence linking several infectious agents with CFS, although no agent has been proven to be a cause of the illness. Most of the infectious agents that have been linked to CFS are able to produce a persistent, often life-long, infection and thus are a constant incitement to the immune system. Most also have been shown to be neuropathogens. The evidence is consistent with the hypothesis that CFS, in some cases, can be triggered and perpetuated by several chronic infections that directly or indirectly affect the nervous system, and that symptoms are a reflection of the immune response to the infection.

Cerebrovascular disease in central nervous system infections.

Cerebrovascular disease is a complication of a variety of infections affecting the central nervous system (CNS). Infection may cause vasculitis affecting primarily the vessels at the base of the brain in the setting of meningitis; an immune-mediated parainfectious process leading to vasospasm or thrombosis; or a hypercoagulable state in combination with endothelial dysfunction resulting from activation of inflammatory and procoagulant cascades. Although systemic signs and symptoms may be present to aid in the diagnosis, cerebral infarction secondary to infection may be indistinguishable from more typical causes of stroke. Confirmation of an infectious vasculitis may also be challenging, as brain biopsy, the gold standard for diagnosis, is rarely pursued. In many CNS infections, vascular complications portend a poor prognosis as they are often associated with devastating neurologic outcomes, including death, underscoring the importance of early recognition and appropriate therapy. In this review, we address bacterial, viral, fungal, and parasitic causes of cerebrovascular disease.