Evidence-based guidelines for the management of patients with Lyme disease, human granulocytic anaplasmosis (formerly known as human granulocytic ehrlichiosis), and babesiosis were prepared by an expert panel of the Infectious Diseases Society of America. These updated guidelines replace the previous treatment guidelines published in 2000 (Clin Infect Dis 2000; 31[Suppl 1]:1-14). The guidelines are intended for use by health care providers who care for patients who either have these infections or may be at risk for them. For each of these Ixodes tickborne infections, information is provided about prevention, epidemiology, clinical manifestations, diagnosis, and treatment. Tables list the doses and durations of antimicrobial therapy recommended for treatment and prevention of Lyme disease and provide a partial list of therapies to be avoided. A definition of post-Lyme disease syndrome is proposed.

BACKGROUND Whole-genome sequencing may revolutionize medical diagnostics through rapid identification of alleles that cause disease. However, even in cases with simple patterns of inheritance and unambiguous diagnoses, the relationship between disease phenotypes and their corresponding genetic changes can be complicated. Comprehensive diagnostic assays must therefore identify all possible DNA changes in each haplotype and determine which are responsible for the underlying disorder. The high number of rare, heterogeneous mutations present in all humans and the paucity of known functional variants in more than 90% of annotated genes make this challenge particularly difficult. Thus, the identification of the molecular basis of a genetic disease by means of whole-genome sequencing has remained elusive. We therefore aimed to assess the usefulness of human whole-genome sequencing for genetic diagnosis in a patient with Charcot–Marie–Tooth disease. METHODS We identified a family with a recessive form of Charcot–Marie–Tooth disease for which the genetic basis had not been identified. We sequenced the whole genome of the proband, identified all potential functional variants in genes likely to be related to the disease, and genotyped these variants in the affected family members. RESULTS We identified and validated compound, heterozygous, causative alleles in SH3TC2 (the SH3 domain and tetratricopeptide repeats 2 gene), involving two mutations, in the proband and in family members affected by Charcot–Marie–Tooth disease. Separate subclinical phenotypes segregated independently with each of the two mutations; heterozygous mutations confer susceptibility to neuropathy, including the carpal tunnel syndrome. CONCLUSIONS As shown in this study of a family with Charcot–Marie–Tooth disease, whole-genome sequencing can identify clinically relevant variants and provide diagnostic information to inform the care of patients.

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Von Hippel-Lindau disease (VHL) is an autosomal dominant disorder with inherited susceptibility to various forms of cancer, including hemangioblastomas of the central nervous system, phaeochromocytomas, pancreatic malignancies, and renal cell carcinomas. Renal cell carcinomas constitute a particularly frequent cause of death in this disorder, occurring as bilateral and multifocal tumours, and presenting at an earlier age than in sporadic, non-familial cases of this tumour type. We report here that the VHL gene is linked to the locus encoding the human homologoue of the RAF1 oncogene, which maps to chromosome 3p25 (ref. 4). Crossovers with the VHL locus suggest that the defect responsible for the VHL phenotype is not a mutation in the RAF1 gene itself. An alternative or prior event to oncogene activation in tumour formation may be the inactivation of a putative 'tumour suppressor' which can be associated with both the inherited and sporadic forms of the cancer. Sporadic renal cell carcinomas have previously been associated with the loss of regions on chromosome 3p (refs 5, 6). Consequently, sporadic and VHL-associated forms of renal cell carcinoma might both result from alterations causing loss of function of the same 'tumour suppressor' gene on this chromosome.

Objective: To provide evidence-based recommendations on the treatment of nervous system Lyme disease and post-Lyme syndrome. Three questions were addressed: 1) Which antimicrobial agents are effective? 2) Are different regimens preferred for different manifestations of nervous system Lyme disease? 3) What duration of therapy is needed? Methods: The authors analyzed published studies ) using a structured review process to classify the evidence related to the questions posed. Results: The panel reviewed 353 abstracts which yielded 112 potentially relevant articles that were reviewed, from which 37 articles were identified that were included in the analysis. Conclusions:There are sufficient data to conclude that, in both adults and children, this nervous system infection responds well to penicillin, ceftriaxone, cefotaxime, and doxycycline (Level B recommendation). Although most studies have used parenteral regimens for neuroborreliosis, several European studies support use of oral doxycycline in adults with meningitis, cranial neuritis, and radiculitis (Level B), reserving parenteral regimens for patients with parenchymal CNS involvement, other severe neurologic symptomatology, or failure to respond to oral regimens. The number of children (Ն8 years of age) enrolled in rigorous studies of oral vs parenteral regimens has been smaller, making conclusions less statistically compelling. However, all available data indicate results are comparable to those observed in adults. In contrast, there is no compelling evidence that prolonged treatment with antibiotics has any beneficial effect in post-Lyme syndrome (Level A). NEUROLOGY 2007;69:91-102