Tracey A. Cho

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.

T-cell activation and memory phenotypes in cerebrospinal fluid during HIV infection.

We characterized T cell phenotypes in 74 paired blood and cerebrospinal fluid (CSF) samples of HIV-infected and uninfected persons using four-color flow cytometry. CD4+ and CD8+ T cells subsets were further characterized by identifying activated/resting and memory/naive subsets in CSF and blood using the markers CD38/HLA-DR and CD45RA/CD62L, respectively. With and without HIV-infection, the proportion of CD4+ T cells and memory T cells among T cells in CSF was higher compared to blood. In HIV-infection, activated CD4+ and CD8+ T cells in CSF were more abundant than in uninfected controls. As expected, combination antiretroviral therapy (ART) reduced T cell activation in CSF and blood.

Infliximab for the treatment of CNS sarcoidosis: A multi-institutional series

Objective: To describe clinical and imaging responses in neurosarcoidosis to infliximab, a monoclonal antibody against tumor necrosis factor–α. Methods: Investigators at 6 US centers retrospectively identified patients with CNS sarcoidosis treated with infliximab, including only patients with definite or probable neurosarcoidosis following rigorous exclusion of other causes. Results: Of 66 patients with CNS sarcoidosis (27 definite, 39 probable) treated with infliximab for a median of 1.5 years, the mean age was 47.5 years at infliximab initiation (SD 11.7, range 24–71 years); 56.1% were female; 62.1% were white, 37.0% African American, and 3% Hispanic. Sarcoidosis was isolated to the CNS in 19.7%. Using infliximab doses ranging from 3 to 7 mg/kg every 4–8 weeks, MRI evidence of a favorable treatment response was observed in 82.1% of patients with imaging follow-up (n = 56), with complete remission of active disease in 51.8% and partial MRI improvement in 30.1%; MRI worsened in 1 patient (1.8%). There was clinical improvement in 77.3% of patients, with complete neurologic recovery in 28.8%, partial improvement in 48.5%, clinical stability in 18.2%, worsening in 3%, and 1 lost to follow-up. In 16 patients in remission when infliximab was discontinued, the disease recurred in 9 (56%), typically in the same neuroanatomic location. Conclusions: Most patients with CNS sarcoidosis treated with infliximab exhibit favorable imaging and clinical treatment responses, including some previously refractory to other immunosuppressive treatments. Classification of evidence: This study provides Class IV evidence that for patients with CNS sarcoidosis infliximab is associated with favorable imaging and clinical responses.

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.

Clinical Aspects of Headache in HIV

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.

Case records of the Massachusetts General Hospital. Case 30-2013. A 19-year-old man with otalgia, slurred speech, and ataxia.

Dr. Isaac I. Bogoch (Infectious Diseases): A 19-year-old man was admitted to this hospital in early spring because of otalgia, slurred speech, and ataxia. The patient had been well until approximately 1 month before admission, when fatigue, fever, pharyngitis, and lymphadenopathy developed. Twenty-five days before admission, he went to another medical facility, where a test for streptococcal pharyngitis was negative. Eight days later, a heterophile antibody test was positive and the hematocrit, hemoglobin, and blood levels of total protein, albumin, and total and direct bilirubin were normal; other test results are shown in Table 1. A diagnosis of infectious mononucleosis due to Epstein–Barr virus (EBV) infection was made. Two weeks before admission, dysphagia developed and pain and decreased hearing occurred in the right ear. On repeat evaluation, a diagnosis of otitis media was made, and prednisone (45 mg daily, for 5 days) and amoxicillin (for 2 days) were administered, followed by azithromycin (for 3 days). Eight days before admission, severe otalgia developed. On examination by an otolaryngologist, there was perforation of the right tympanic membrane, with bloody purulent material in the external ear canal. Oral cefuroxime (500 mg twice daily) and an otic suspension of topical ciprofloxacin and dexamethasone were prescribed. Two days later, increasing unsteadiness developed; the patient fell several times during the next 5 days. The day before admission, he returned to the otolaryngologist; on examination, there was an effusion in the right middle ear. Myringotomy, with fluid aspiration, was performed. After the procedure, transient unsteadiness occurred, with vomiting; ear pain lessened, and hearing partially improved. After returning home, the patient noted slurred speech, clumsiness with movements, and increasing gait imbalance. Later that night, he went to the emergency department at another hospital. Ceftriaxone (1 g) was administered, and he was transferred to the emergency department at this hospital. The patient reported fullness and decreased hearing in the right ear, weight loss of 4.5 kg, and persistent fatigue during the previous month, without neck stiffness, headache, photophobia, changes in vision, tinnitus, vertigo, sensory abnormalities, or difficulty with comprehension. He had a history of acne, asthma, and otitis media

Case 30-2013

Dr. Isaac I. Bogoch (Infectious Diseases): A 19-year-old man was admitted to this hospital in early spring because of otalgia, slurred speech, and ataxia. The patient had been well until approximately 1 month before admission, when fatigue, fever, pharyngitis, and lymphadenopathy developed. Twenty-five days before admission, he went to another medical facility, where a test for streptococcal pharyngitis was negative. Eight days later, a heterophile antibody test was positive and the hematocrit, hemoglobin, and blood levels of total protein, albumin, and total and direct bilirubin were normal; other test results are shown in Table 1. A diagnosis of infectious mononucleosis due to Epstein–Barr virus (EBV) infection was made. Two weeks before admission, dysphagia developed and pain and decreased hearing occurred in the right ear. On repeat evaluation, a diagnosis of otitis media was made, and prednisone (45 mg daily, for 5 days) and amoxicillin (for 2 days) were administered, followed by azithromycin (for 3 days). Eight days before admission, severe otalgia developed. On examination by an otolaryngologist, there was perforation of the right tympanic membrane, with bloody purulent material in the external ear canal. Oral cefuroxime (500 mg twice daily) and an otic suspension of topical ciprofloxacin and dexamethasone were prescribed. Two days later, increasing unsteadiness developed; the patient fell several times during the next 5 days. The day before admission, he returned to the otolaryngologist; on examination, there was an effusion in the right middle ear. Myringotomy, with fluid aspiration, was performed. After the procedure, transient unsteadiness occurred, with vomiting; ear pain lessened, and hearing partially improved. After returning home, the patient noted slurred speech, clumsiness with movements, and increasing gait imbalance. Later that night, he went to the emergency department at another hospital. Ceftriaxone (1 g) was administered, and he was transferred to the emergency department at this hospital. The patient reported fullness and decreased hearing in the right ear, weight loss of 4.5 kg, and persistent fatigue during the previous month, without neck stiffness, headache, photophobia, changes in vision, tinnitus, vertigo, sensory abnormalities, or difficulty with comprehension. He had a history of acne, asthma, and otitis media

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.

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.

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).