Coding of Neuroinfectious Diseases.

Accurate coding is an important function of neurologic practice. This contribution to Continuum is part of an ongoing series that presents helpful coding information along with examples related to the issue topic. Tips for diagnosis coding, Evaluation and Management coding, procedure coding, or a combination are presented, depending on which is most applicable to the subject area of the issue.

Infective Causes of Epilepsy.

A wide range of infections of the central nervous system are responsible for both acute seizures and epilepsy. The pathogenesis and clinical semiology of the seizure disorders vary widely between the infective pathogens. The exact mechanisms underlying this are poorly understood, but appear, at least in part, to relate to the pathogen; the degree of cortical involvement; delays in treatment; and the host inflammatory response. The treatment of infective causes of seizures involves both symptomatic treatment with antiepileptic drugs and direct treatment of the underlying condition. In many cases, early treatment of the infection may affect the prognosis of the epilepsy syndrome. The greatest burden of acute and long-term infection-related seizures occurs in resource-poor settings, where both clinical and research facilities are often lacking to manage such patients adequately. Nevertheless, education programs may go a long way toward addressing the stigma, leading to improved diagnosis, management, and ultimately to better quality of life.

Cerebrospinal fluid Alzheimer's biomarker profiles in CNS infections.

The cerebrospinal fluid (CSF) biomarker profile in Alzheimer's disease (AD) is characterized by decreased beta amyloid (Aß(1-42)), increased total and hyperphosphorylated tau (t-tau and p-tau, respectively), which is a useful diagnostic tool and gives insight in the pathogenesis of AD. It is of importance to study how these biomarkers react in other CNS diseases; therefore, we decided to analyse amyloid and tau biomarkers in different CNS infections. We also included analysis of soluble amyloid precursor proteins (sAPPα and -ß). CSF Aß(1-42), sAPPα and -ß, t-tau and p-tau were analysed in bacterial meningitis (n = 12), Lyme neuroborreliosis (n = 13), herpes simplex virus type 1 (HSV-1) encephalitis (n = 10), HIV-associated dementia (HAD) (n = 21), AD (n = 21) and healthy controls (n = 42). Concurrent with AD, Aß(1-42) was decreased in all groups except neuroborreliosis compared to controls. HSV-1 encephalitis, bacterial meningitis and HAD showed lower concentrations of sAPPα and -ß compared to AD. T-tau was increased in AD and HSV-1 encephalitis compared to all other groups. P-tau was higher in AD and HSV-1 encephalitis compared to bacterial meningitis, HAD and control. Decreased CSF Aß(1-42), sAPPα and -ß in various CNS infections imply an effect of neuroinflammation on amyloid metabolism which is similar in regard to AD concerning Aß(1-42), but differs concerning sAPPα and -ß. These results clearly indicate different pathologic pathways in AD and infectious CNS disease and may provide help in the differential biomarker diagnostics. Increased p-tau in HSV-1 encephalitis probably reflect acute neuronal damage and necrosis.

Classification of acute encephalopathy in respiratory syncytial virus infection.

Infection with respiratory syncytial virus (RSV) is known to be associated with central nervous system symptoms such as convulsions. We investigated cytokines, nitrogen oxide (NO)( x ), and the viral genome in cerebrospinal fluid (CSF) obtained from children with RSV infection-related convulsions or central nervous symptoms and compared the data with type of encephalopathy. Of nine patients enrolled (six boys and three girls; aged 10 days-3 years), one metabolic error, five excitotoxicity, one cytokine storm, and two hypoxia cases were found. The patients presented with unilateral convulsions, generalized convulsions, and convulsions following cardiopulmonary arrest, apnea, and nuchal rigidity. In all patients, a rapid check for RSV of nasal fluid was positive. The RSV genome (subgroup A) was detected in the CSF of five of the nine patients; two patients with hypoxic encephalopathy were negative for the RSV genome. The CSF interleukin (IL)-6 levels were high only in patients with the excitotoxicity and cytokine storm type of encephalopathy. NO( x ) levels were high in all the subject cases. In the excitotoxicity type, NO( x ) levels were significantly higher than those in the control and other groups. NO( x ) level may become an important parameter for the diagnosis and classification of acute encephalopathy in RSV. Strategies to treat each type of encephalopathy, targeting cytokines and free radicals, should be established.

Continuous electroencephalographic monitoring in critically ill patients with central nervous system infections.

OBJECTIVES: To determine the prevalence, predictors, and clinical significance of electrographic seizures (ESz) and other continuous electroencephalographic monitoring findings in critically ill patients with central nervous system infections. DESIGN: Retrospective cohort study. SETTING: Eighteen-bed neurocritical care unit. PATIENTS: We identified 42 consecutive patients with primary central nervous system infection (viral, 27 patients [64%]; bacterial, 8 patients [18%]; and fungal or parasitic, 7 patients [17%]) who underwent continuous electroencephalographic monitoring between January 1, 1996, and February 28, 2007. MAIN OUTCOME MEASURES: Presence of ESz or periodic epileptiform discharges (PEDs). RESULTS: Electrographic seizures were recorded in 14 patients (33%), and PEDs were recorded in 17 patients (40%). Twenty patients (48%) had either PEDs or ESz. Of the 14 patients with ESz, only 5 (36%) had a clinical correlate. Periodic epileptiform discharges (odds ratio=13.4; P=.001) and viral cause (odds ratio=13.0; P=.02) were independently associated with ESz. Both ESz (odds ratio=5.9; P=.02) and PEDs (odds ratio=6.1; P=.01) were independently associated with poor outcome at discharge (severe disability, vegetative state, or death). CONCLUSIONS: In patients with central nervous system infections undergoing continuous electroencephalographic monitoring, ESz and/or PEDs were frequent, occurring in 48% of our cohort. More than half of the ESz had no clinical correlate. Both ESz and PEDs were independently associated with poor outcome. Additional studies are needed to determine whether prevention or treatment of these electrographic findings improves outcome.

Diagnosis-dependent misclassification of infections using administrative data variably affected incidence and mortality estimates in ICU patients.

OBJECTIVE: To determine the accuracy of hospital discharge diagnoses in identifying severe infections among intensive care unit (ICU) patients, and estimate the impact of misclassification on incidence and 1-year mortality. STUDY DESIGN AND SETTING: Sepsis, pneumonia, and central nervous system (CNS) infections among 7,615 ICU admissions were identified using ICD-9 and ICD-10 diagnoses from the Swedish hospital discharge register (HDR). Sensitivity, specificity, and likelihood ratios were calculated using ICU database diagnoses as reference standard, with inclusion in sepsis trials (IST) as secondary reference for sepsis. RESULTS: CNS infections were accurately captured (sensitivity 95.4% [confidence interval (CI)=86.8-100] and specificity 99.6% [CI=99.4-99.8]). Community-acquired sepsis (sensitivity 51.1% [CI=41.0-61.2] and specificity 99.4% [CI=99.2-99.6]) and primary pneumonia (sensitivity 38.2% [CI=31.2-45.2] and specificity 98.6% [CI=98.2-99.0]) were more accurately detected than sepsis and pneumonia in general. One-year mortality was accurately estimated for primary pneumonia but underestimated for community-acquired sepsis. However, there were only small differences in sensitivity and specificity between HDR and ICU data in the ability to identify IST. ICD-9 appeared more accurate for sepsis, whereas ICD-10 was more accurate for pneumonia. CONCLUSION: Accuracy of hospital discharge diagnoses varied depending on diagnosis and case definition. The pattern of misclassification makes estimates of relative risk more accurate than estimates of absolute risk.

Infectious inflammation of the CNS involves activation of mitogen-activated protein kinase and AKT proteins in CSF in humans.

The mitogen-activated protein kinases (MAPKs) and the AKT are interacting proteins that serve as transmitters of numerous extracellular signals to their intracellular targets, thereby regulating many cellular processes, such as proliferation, differentiation, development or stress responses. Whereas a large amount of information about the MAPKs/AKT participation in biological processes is available, less is known about their role in human diseases. We postulated that the MAPKs/AKT could be involved in inflammatory processes of the central nervous system (CNS) in humans and we investigated the CSF of 12 patients with viral infection of the CNS for the presence of the distinct components of these cascades. The cerebrospinal fluid (CSF) of 18 individuals who underwent a lumbar puncture for diagnostic purposes served as controls. Six patients with inflammatory disease of the CNS revealed the presence of activated ERK. In five patients p38MAPK was detected, in three in its activated form. The activity of AKT could be demonstrated in four patients. JNK was not found. None of the control patients showed the presence of MAPK enzymes. The mean CSF cellularity was higher in MAPK-positive than in MAPKnegative patients. There was no difference in mean age or gender between the patients and controls, or between the MAPK- and AKT-positive or -negative patients. Our work demonstrates that the MAPK and AKT cascades might participate in inflammatory processes of the CNS. As selective inhibitors of the MAPKs are available, their application in the future might reduce an inappropriate inflammatory response and thus limit brain damage in severe cases of meningoencephalitis.

Enfermedad neurologica por adenovirus / Neurologic disease due to adenovirus infection

El objetivo de este trabajo fue determinar la prevalencia de adenovirus (ADV) en las infecciones del sistema nervioso central (SNC). Se analizaron 108 muestras de líquido cefalorraquídeo (LCR) provenientes de 79 casos de encefalitis, 7 meningitis y 22 de otras patologías neurológicas, recibidas en el período 2000-2002. Cuarenta y nueve (47.35%) se obtuvieron de pacientes inmunocomprometidos. La presencia de ADV se investigó mediante reacción en cadena de la polimerasa en formato anidado (Nested-PCR). La identificación del genogrupo se realizó mediante análisis filogenético de la secuencia nucleotídica parcial de la región que codifica para la proteína del hexón. Se detectó la presencia de ADV en 6 de 108 (5.5%) muestras de LCR analizadas. Todos los casos positivos pertenecieron a pacientes con encefalitis que fueron 79, (6/79, 7.6%). No se observó diferencia estadísticamente significativa entre los casos de infección por ADV en pacientes inmunocomprometidos e inmunocompetentes (p>0.05). Las cepas de ADV detectadas se agruparon en los genogrupos B1 y C. En conclusión, nuestros resultados describen el rol de los ADV en las infecciones neurológicas en Argentina. La información presentada contribuye al conocimiento de su epidemiología, en particular en casos de encefalitis. (AU)

Enfermedad neurologica por adenovirus / Neurologic disease due to adenovirus infection

El objetivo de este trabajo fue determinar la prevalencia de adenovirus (ADV) en las infecciones del sistema nervioso central (SNC). Se analizaron 108 muestras de líquido cefalorraquídeo (LCR) provenientes de 79 casos de encefalitis, 7 meningitis y 22 de otras patologías neurológicas, recibidas en el período 2000-2002. Cuarenta y nueve (47.35%) se obtuvieron de pacientes inmunocomprometidos. La presencia de ADV se investigó mediante reacción en cadena de la polimerasa en formato anidado (Nested-PCR). La identificación del genogrupo se realizó mediante análisis filogenético de la secuencia nucleotídica parcial de la región que codifica para la proteína del hexón. Se detectó la presencia de ADV en 6 de 108 (5.5%) muestras de LCR analizadas. Todos los casos positivos pertenecieron a pacientes con encefalitis que fueron 79, (6/79, 7.6%). No se observó diferencia estadísticamente significativa entre los casos de infección por ADV en pacientes inmunocomprometidos e inmunocompetentes (p>0.05). Las cepas de ADV detectadas se agruparon en los genogrupos B1 y C. En conclusión, nuestros resultados describen el rol de los ADV en las infecciones neurológicas en Argentina. La información presentada contribuye al conocimiento de su epidemiología, en particular en casos de encefalitis.

Making sense of central nervous system infections at the reference desk.

This paper discusses concepts and terminology of some aspects of infections of the central nervous system as it relates to medical reference work. Details of anatomic, biochemical, and pathologic processes are not discussed. Specific terminology involved in this area will be reviewed in order to help ensure a good approach to developing prudent strategies for database searching of the medical literature. MeSH thesauri terms are discussed and text word synonyms are presented that provide tools for thorough searching techniques. Commonly used medical jargon for this area is also explained. Examples of specific search strategies are illustrated.

Fetal brain infections.

INTRODUCTION: Congenital infections can cause severe brain damage. As a result, it is very important to identify them early in their course so that treatment can be administered to the mother, if possible. The role of imaging is to determine the presence, if any, and the extent of brain damage in the infected fetus. Although MRI is most commonly used as an adjunct to sonography, when clinical suspicion is high in the setting of a normal ultrasound or to better define abnormalities detected by ultrasound, MRI is routinely used in toxoplasmosis seroconversion to definitively rule out brain lesions, even when the ultrasound scan is considered normal. MRI is also used serially throughout the pregnancy to check for the development of brain abnormalities; medical treatment results in excellent clinical outcome if the brain is normal. DISCUSSION: This article describes the indications, techniques, and findings that will allow proper use of fetal MRI in the setting of congenital infections.

Infections of the central nervous system in transplant recipients.

Central nervous system (CNS) infections, accounting for 4-29% of CNS lesions in transplant recipients, are a significant post-transplant complication. Focal CNS infectious lesions or brain abscesses have been documented in 0.36-1% of the transplant recipients. Mycelial fungi, particularly Aspergillus, are by far the most frequent etiologies of post-transplant brain abscesses. Bacteria, with the exception of Nocardia, are rarely associated with brain abscesses in transplant recipients. Time of onset and concurrent extraneural lesions have implications relevant towards invasive diagnostic procedures in transplant recipients with brain abscesses. Meningoencephalitis in transplant recipients is predominantly due to viruses, e.g., herpesviruses, and less frequently due to Listeria monocytogenes, Toxoplasma gondii, and Cryptococcus. Despite a wide, and at times perplexing array of opportunistic pathogens that can cause CNS infections, the temporal association of the infection with the time elapsed since transplantation, risk factors, clinical manifestations, and neuroimaging characteristics of the lesion can allow a reasoned and rational approach towards the recognition, diagnosis, and appropriate management of CNS infections in transplant recipients.

Tuberculosis of the central nervous system.

Tuberculous involvement of the brain and spinal cord are common neurological disorders in developing countries and have recently shown a resurgence in developed ones. Tuberculous meningitis is an important manifestation and is associated with high morbidity and mortality. Diagnosis is based on clinical features, cerebrospinal fluid changes, and imaging characteristics. Bacteriological confirmation is not possible in all cases as serological tests do not have sufficient sensitivity and specificity. The polymerase chain reaction shows promise for the future. Appropriate chemotherapeutic agents should be administered as early as possible, although there is no unanimity concerning chemotherapeutic regimens or optimal duration of treatment. The patient's clinical stage at presentation is the most important prognostic factor. The role of corticosteroids is controversial but they should be administered to all patients presenting in stage III. Surgical procedures are directed at management of the hydrocephalus. Focal lesions, intracranial tuberculomas, and tuberculous abscesses, are usually located in cerebral or cerebellar hemispheres, uncommonly in brainstem and very rarely in spinal cord. They do not usually require surgical intervention and respond well to antituberculous treatment, along with corticosteroids.

Infecciones del sistemas mervioso central

La gravedad que implica toda infección del sistema nervioso central, hace indispensable el conocimiento de sus signos, síntomas y tratamiento