Clinical management of infectious cerebral vasculitides

Cryptococcosis is a global invasive mycosis associated with significant morbidity and mortality. These guidelines for its management have been built on the previous Infectious Diseases Society of America guidelines from 2000 and include new sections. There is a discussion of the management of cryptococcal meningoencephalitis in 3 risk groups: (1) human immunodeficiency virus (HIV)-infected individuals, (2) organ transplant recipients, and (3) non-HIV-infected and nontransplant hosts. There are specific recommendations for other unique risk populations, such as children, pregnant women, persons in resource-limited environments, and those with Cryptococcus gattii infection. Recommendations for management also include other sites of infection, including strategies for pulmonary cryptococcosis. Emphasis has been placed on potential complications in management of cryptococcal infection, including increased intracranial pressure, immune reconstitution inflammatory syndrome (IRIS), drug resistance, and cryptococcomas. Three key management principles have been articulated: (1) induction therapy for meningoencephalitis using fungicidal regimens, such as a polyene and flucytosine, followed by suppressive regimens using fluconazole; (2) importance of early recognition and treatment of increased intracranial pressure and/or IRIS; and (3) the use of lipid formulations of amphotericin B regimens in patients with renal impairment. Cryptococcosis remains a challenging management issue, with little new drug development or recent definitive studies. However, if the diagnosis is made early, if clinicians adhere to the basic principles of these guidelines, and if the underlying disease is controlled, then cryptococcosis can be managed successfully in the vast majority of patients.

SUMMARY AND KEY RECOMMENDATIONS: The aim of these guidelines is to describe a practical but evidence-based approach to the diagnosis and treatment of central nervous system tuberculosis in children and adults. We have presented guidance on tuberculous meningitis (TBM), intra-cerebral tuberculoma without meningitis, and tuberculosis affecting the spinal cord. Our key recommendations are as follows: 1. TBM is a medical emergency. Treatment delay is strongly associated with death and empirical anti-tuberculosis therapy should be started promptly in all patients in whom the diagnosis of TBM is suspected. Do not wait for microbiological or molecular diagnostic confirmation. 2. The diagnosis of TBM is best made with lumbar puncture and examination of the cerebrospinal fluid (CSF). Suspect TBM if there is a CSF leucocytosis (predominantly lymphocytes), the CSF protein is raised, and the CSF:plasma glucose is <50%. The diagnostic yield of CSF microscopy and culture for Mycobacterium tuberculosis increases with the volume of CSF submitted; repeat the lumbar puncture if the diagnosis remains uncertain. 3. Imaging is essential for the diagnosis of cerebral tuberculoma and tuberculosis involving the spinal cord, although the radiological appearances do not confirm the diagnosis. A tissue diagnosis (by histopathology and mycobacterial culture) should be attempted whenever possible, either by biopsy of the lesion itself, or through diagnostic sampling from extra-neural sites of disease e.g. lung, gastric fluid, lymph nodes, liver, bone marrow. 4. Treatment for all forms of CNS tuberculosis should consist of 4 drugs (isoniazid, rifampicin, pyrazinamide, ethambutol) for 2 months followed by 2 drugs (isoniazid, rifampicin) for at least 10 months. Adjunctive corticosteroids (either dexamethasone or prednisolone) should be given to all patients with TBM, regardless of disease severity. 5. Children with CNS tuberculosis should ideally be managed by a paediatrician with familiarity and expertise in paediatric tuberculosis or otherwise with input from a paediatric infectious diseases unit. The Children's HIV Association of UK and Ireland (CHIVA) provide further guidance on the management of HIV-infected children (www.chiva.org.uk). 6. All patients with suspected or proven tuberculosis should be offered testing for HIV infection. The principles of CNS tuberculosis diagnosis and treatment are the same for HIV infected and uninfected individuals, although HIV infection broadens the differential diagnosis and anti-retroviral treatment complicates management. Tuberculosis in HIV infected patients should be managed either within specialist units by physicians with expertise in both HIV and tuberculosis, or in a combined approach between HIV and tuberculosis experts. The co-administration of anti-retroviral and anti-tuberculosis drugs should follow guidance issued by the British HIV association (www.bhiva.org).

Varicella zoster virus-induced vasculopathy and postherpes zoster attack stroke syndromes have been reported previously; nevertheless, data regarding the exact prevalence and risk of stroke occurring postherpes zoster attack are still lacking. This study aims to investigate the frequency and risk of stroke after a herpes zoster attack using a nationwide, population-based study of a retrospective cohort design. Method- A total of 7760 patients who had received treatment for herpes zoster between 1997 and 2001 were included and matched with 23 280 randomly selected subjects. A 1-year stroke-free survival rate was then estimated using the Kaplan-Meier method. After adjusting for potential confounders, Cox proportional hazard regressions were carried out to compute the adjusted 1-year survival rate. Of the sampled patients, 439 patients (1.41%) developed strokes within the 1-year follow-up period, that is, 133 individuals (1.71% of the patients with herpes zoster) from the study cohort and 306 individuals (1.31% of patients in the comparison cohort) from the comparison cohort. The log rank test indicated that patients with herpes zoster had significantly lower 1-year stroke-free survival rates than the control (P<0.001). The adjusted hazard ratios of stroke after herpes zoster and herpes zoster ophthalmicus during the 1-year follow-up period were 1.31 and 4.28, respectively. The risk for stroke increased after a zoster attack. Although varicella zoster virus vasculopathy is a well-documented complication that may induce a stroke postherpes zoster attack, it does not fully account for the unexpectedly high risk of stroke in these patients.