Prion Disease.

Prion diseases are a phenotypically diverse set of disorders characterized by protease-resistant abnormally shaped proteins known as prions. There are three main groups of prion diseases, termed sporadic (Creutzfeldt-Jakob disease [CJD], sporadic fatal insomnia, and variably protease-sensitive prionopathy), genetic (genetic CJD, fatal familial insomnia, and Gerstmann-Straussler-Scheinker syndrome), and acquired (kuru, variant CJD, and iatrogenic CJD). This article will review the pathophysiology, genetics, clinical presentations, and diagnostic challenges in patients with prion disease. Case discussions, images, and tables will be used to highlight important characteristics of prion disease and prion mimics.

Human Chronic Necrotizing Granulomatous Meningoencephalitis: A Novel Case Report.

Necrotizing and granulomatous meningoencephalitis are common central nervous system diseases known to affect canines. To date, necrotizing granulomatous meningoencephalitis has yet to be described in humans. Current studies of presumed pathogenesis and possible treatment options have only been described in canines. This is a case report of a 55-year-old female patient who was diagnosed with necrotizing granulomatous meningoencephalitis in the setting of new-onset neurological symptoms without any infectious or malignant source.

Herpesvirus Infections of the Nervous System.

PURPOSE OF REVIEW: This article reviews the spectrum of neurologic disease associated with human herpesvirus infections. RECENT FINDINGS: As more patients are becoming therapeutically immunosuppressed, human herpesvirus infections are increasingly common. Historically, infections with human herpesviruses were described as temporal lobe encephalitis caused by herpes simplex virus type 1 or type 2. More recently, however, additional pathogens, such as varicella-zoster virus, Epstein-Barr virus, cytomegalovirus, and human herpesvirus 6 have been identified to cause serious neurologic infections. As literature emerges, clinical presentations of herpesvirus infections have taken on many new forms, becoming heterogeneous and involving nearly every location along the neuraxis. Advanced diagnostic methods are now available for each specific pathogen in the herpesvirus family. As data emerge on viral resistance to conventional therapies, newer antiviral medications must be considered. SUMMARY: Infections from the herpesvirus family can have devastating neurologic outcomes without prompt and appropriate treatment. Clinical recognition of symptoms and appropriate advanced testing are necessary to correctly identify the infectious etiology. Knowledge of secondary neurologic complications of disease is equally important to prevent additional morbidity and mortality. This article discusses infections of the central and peripheral nervous systems caused by herpes simplex virus type 1 and type 2, varicella-zoster virus, Epstein-Barr virus, cytomegalovirus, and human herpesvirus 6. The pathophysiology, epidemiology, clinical presentations of disease, diagnostic investigations, imaging characteristics, and treatment for each infectious etiology are discussed in detail.

Diagnostic Approach to Chronic Meningitis.

Chronic meningitis is defined as cerebrospinal fluid pleocytosis that persists for at least 4 weeks without spontaneous resolution. The differential diagnosis of chronic meningitis is broad, encompassing 4 main categories, including infectious, autoimmune, neoplastic, and idiopathic. Up to one-third of cases have no discernible cause, making chronic meningitis a diagnostic dilemma for many clinicians. This article suggests a diagnostic approach to chronic meningitis using clinical history, key examination findings, selective advanced testing, and neuroimaging. Case presentations demonstrate application of a diagnostic algorithm, followed by a brief discussion on common infectious pathogens, autoimmune conditions, and neoplastic disease with selected treatment regimens.

Chronic Autoimmune Meningoencephalitis and Periodic Fever Syndrome Treated with Anakinra.

We report the case of a 63-year-old male diagnosed with chronic autoimmune mediated meningoencephalitis and periodic cyclical fever syndrome. After 2 years of failed conventional treatment and recurrent hospitalizations, anakinra treatment (an interleukin-1 [IL-1] receptor antagonist) was trialed which resulted in full recovery. As evidenced by this case, anakinra can be used to treat chronic autoimmune meningitis, which can often be refractory to treatment.

A rare case of rapidly progressive dementia with elevated RT-QuIC and negative 14-3-3 and tau proteins.

Creutzfeldt-Jakob disease (CJD) is characterized by rapidly progressing dementia with death usually occurring within 6 months. There is no verified disease-specific pre-mortem diagnostic test besides brain biopsy. We describe a 66 y old previously high functioning male who presented with a 5 month history of rapidly progressive dementia. Neurological examination revealed a score of 19/30 on MOCA testing. An extensive workup into various causes of dementia including electroencephalography and imaging studies was unremarkable. The cerebrospinal fluid was sent to National Prion Disease Center and it revealed elevated RT-QuIC levels with negative 14-3-3 and T tau proteins. Based on literature review, our case is one of few living subjects with elevated RT-QuIC levels and negative 14-3-3 and tau proteins.

Evaluation and treatment of chronic meningitis.

Chronic meningitis is defined as an inflammatory cerebrospinal fluid (CSF) profile that persists for at least 1 month. The presentation often includes headache, nausea, vomiting, cranial neuropathies, symptoms of elevated intracranial pressure, or focal neurologic deficits. The most common etiologies of chronic meningitis fall into 3 broad categories: infectious, autoimmune, and neoplastic. Evaluation of the patient with suspected chronic meningitis should include a detailed history and physical examination as well as repeated CSF diagnostics, serologic studies, and biopsy of the brain or other abnormal tissue (eg, lymph node or lung), when indicated. Early identification of the etiology and rapid treatment are crucial for improving morbidity and mortality, but potential infectious and neoplastic conditions should be excluded prior to empirically starting steroids or immunosuppressive medications.

Progressive multifocal leukoencephalopathy in patients with multiple sclerosis.

PURPOSE OF REVIEW: Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic infection of the central nervous system. It has been recently associated with selective immunosuppression in patients with multiple sclerosis. This review describes the pathogenesis, clinical presentation, diagnosis, and treatment of natalizumab-associated PML. RECENT FINDINGS: Treatment of multiple sclerosis with natalizumab first involves risk stratifying patients. Clinicians can employ new tools for risk stratification including JC-virus antibody status, prior immunosuppression, and length of natalizumab treatment. These tools can help minimize the risk of developing PML. Identifying patients with natalizumab-associated PML poses a diagnostic challenge for clinicians. Unique clinical features, sensitive laboratory analyses, and advanced MRI techniques have been identified that aid in the diagnosis of natalizumab-associated PML. SUMMARY: There continues to be significant gaps in our understanding of PML pathogenesis and its relationship with therapeutic immunosuppression. There have been advances made in our ability to treat multiple sclerosis, although these have come with the unintended risk of PML. Fortunately, natalizumab-associated PML remains a rare entity compared to multiple sclerosis-associated disability, and the risk may be mitigated with appropriate patient selection, accurate and rapid diagnosis, and aggressive treatment strategies.

Chronic and subacute meningitis.

PURPOSE OF REVIEW: This article describes the background, clinical presentation, diagnosis, and treatment of selected etiologies of subacute and chronic meningitis. Key diagnostic considerations when evaluating a patient presenting with chronic inflammation of the CNS are discussed, and several specific infectious, neoplastic, and autoimmune etiologies are reviewed in detail. RECENT FINDINGS: With recent advancement in serologic and CSF diagnostic testing, specific infectious, neoplastic, or autoimmune etiologies of chronic meningitis can be identified. Eliminating previous diagnostic uncertainty of chronic inflammation in the CNS has led to rapid and specific treatment regimens that ultimately improve patient outcomes. Recent advances in imaging have also aided clinicians in both their diagnostic approach and the detection of inflammatory complications such as hydrocephalus, hemorrhage, and ischemic stroke. SUMMARY: Meningitis is defined as inflammation involving the meninges of the brain and spinal cord. Meningitis can be categorized as acute, subacute, or chronic based on duration of inflammation. This article focuses on the most common causes of subacute and chronic meningitis. Chronic meningitis is commonly defined as inflammation evolving during weeks to months without resolution of CSF abnormalities. Determining the time course of meningitis is important for creating a differential diagnosis. Most organisms causing acute meningitis rarely persist more than a few weeks. Although numerous etiologies of subacute and chronic meningitis have been identified, this article focuses on the most common etiologies: (1) infectious, (2) autoimmune, and (3) neoplastic.