ro13-9904 and Central-Nervous-System-Diseases

Whipple's disease is a multisystemic infection caused by the ubiquitous bacterium Tropheryma whipplei. Immunological host factors enable classical Whipple's disease; however, T. whipplei can be found in three other clinical conditions: healthy colonization, self-limiting infections, and isolated endocarditis. The genetic predisposition of the host rather than the genotype of the bacterium influences the infection. Modern diagnostic methods elucidate the many facets of Whipple's disease. In particular, isolated T. whipplei-induced infective endocarditis can only be diagnosed after valve resection. The sole treatment of Whipple's disease evaluated prospectively comprises intravenous induction therapy with ceftriaxone or meropenem, followed by continuation therapy with oral TMP-SMX. In the case of Immune reconstitution inflammatory syndrome (IRIS) or inflammatory lesions of the CNS in the setting of Whipple's disease, additional treatment with corticosteroids should be considered to avoid severe tissue damage.

Topics: Adrenal Cortex Hormones; Adult; Algorithms; Anti-Bacterial Agents; Biopsy; Carrier State; Ceftriaxone; Central Nervous System Diseases; Child; Diagnosis, Differential; Drug Therapy, Combination; Duodenum; Endocarditis, Bacterial; Gastroscopy; Genetic Predisposition to Disease; Heart Valves; Humans; Immune Reconstitution Inflammatory Syndrome; Meropenem; Thienamycins; Trimethoprim, Sulfamethoxazole Drug Combination; Tropheryma; Whipple Disease

Unlike most bacterial infections, where diagnosis is by identification of the causal organism, diagnosis of infection by Borrelia burgdorferi (Lyme's borreliosis) relies mostly upon indirect techniques. This situation has some short-comings. As long as no technology permits a microbiological diagnosis of this infection, controversy will exist as to the clinical symptoms and the criteria for the cure of the disease. Despite the lack of consensus upon both the clinical definition and the treatment of Lyme's borreliosis, it is widely agreed that the affection is best understood if regarded as a progressive general infectious disease. Indeed, following a bite with local infection, there occurs a fairly rapid dissemination of the spirochaetes. In vivo therapeutic trials have shown the potential effectiveness of beta-lactams and tetracyclines, but no treatment is considered universally effective. Most of the first trials were empirical, as antibiograms were not used. Antibiotic concentrations reached with some oral therapies are too low for the protection of certain sites such as the central nervous system. In vitro studies conducted on various strains of B. burgdorferi both in the US and in Europe are very enlightening. Among the more perplexing results of some of these studies, it is worth noting the high resistance rate of some B. burgdorferi strains to penicillin, reported by Johnson et al. and by Preac Mursic et al. Therapy for Lyme's borreliosis is discussed in light of both the in vivo and in vitro studies.

Topics: Borrelia; Borrelia Infections; Ceftriaxone; Central Nervous System Diseases; Clinical Trials as Topic; Erythema; Humans; Lyme Disease; Penicillins; Random Allocation; Tetracyclines

Unlike most bacterial infections, where diagnosis is by identification of the causal organism, diagnosis of infection by Borrelia burgdorferi (Lyme's borreliosis) relies mostly upon indirect techniques. This situation has some short-comings. As long as no technology permits a microbiological diagnosis of this infection, controversy will exist as to the clinical symptoms and the criteria for the cure of the disease. Despite the lack of consensus upon both the clinical definition and the treatment of Lyme's borreliosis, it is widely agreed that the affection is best understood if regarded as a progressive general infectious disease. Indeed, following a bite with local infection, there occurs a fairly rapid dissemination of the spirochaetes. In vivo therapeutic trials have shown the potential effectiveness of beta-lactams and tetracyclines, but no treatment is considered universally effective. Most of the first trials were empirical, as antibiograms were not used. Antibiotic concentrations reached with some oral therapies are too low for the protection of certain sites such as the central nervous system. In vitro studies conducted on various strains of B. burgdorferi both in the US and in Europe are very enlightening. Among the more perplexing results of some of these studies, it is worth noting the high resistance rate of some B. burgdorferi strains to penicillin, reported by Johnson et al. and by Preac Mursic et al. Therapy for Lyme's borreliosis is discussed in light of both the in vivo and in vitro studies.

Topics: Borrelia; Borrelia Infections; Ceftriaxone; Central Nervous System Diseases; Clinical Trials as Topic; Erythema; Humans; Lyme Disease; Penicillins; Random Allocation; Tetracyclines

Topics: Anti-Bacterial Agents; Ceftriaxone; Central Nervous System Diseases; Chloroquine; Drug Resistance, Bacterial; Drug Therapy, Combination; Humans; Male; Meropenem; Microbial Sensitivity Tests; Minocycline; Thienamycins; Trimethoprim, Sulfamethoxazole Drug Combination; Whipple Disease

In adults a subtle encephalopathy characterized primarily by memory impairment, irritability and somnolence may occur months to years after classic manifestations of Lyme disease. However, only limited information is available about whether there is an equivalent disorder in children.. Case series of five children seen in a Lyme disease clinic in a university referral center for evaluation of neurocognitive symptoms that developed near the onset of infection or months after classic manifestations of Lyme disease. The diagnosis was based on clinical symptoms, serologic reactivity to Borrelia burgdorferi and intrathecal antibody production to the spirochete. Evaluation included detailed neuropsychologic testing. After evaluation the children were treated with intravenous ceftriaxone for 2 or 4 weeks. Follow-up was done in the clinic and a final assessment was made by telephone 2 to 7 years after treatment.. Along with or months after erythema migrans, cranial neuropathy or Lyme arthritis, the five children developed behavioral changes, forgetfulness, declining school performance, headache or fatigue and in two cases a partial complex seizure disorder. All five patients had IgG antibody responses to B. burgdorferi in serum as well as intrathecal IgG antibody production to the spirochete. Two patients had CSF pleocytoses and three did not. Despite normal intellectual functioning the five children had mild to moderate deficits in auditory or visual sequential processing. After ceftriaxone therapy, the four children in whom follow-up information was available experienced gradual improvement in symptoms.. Children may develop neurocognitive symptoms along with or after classic manifestations of Lyme disease. This may represent an infectious or postinfectious encephalopathy related to B. burgdorferi infection.

Topics: Adolescent; Antibodies, Bacterial; Borrelia burgdorferi Group; Ceftriaxone; Central Nervous System Diseases; Cephalosporins; Child; Cognition Disorders; Female; Humans; Immunoglobulin G; Lyme Disease; Male; Neuropsychological Tests

Topics: Ceftriaxone; Central Nervous System Diseases; Humans; Recurrence; Tetracycline; Trimethoprim, Sulfamethoxazole Drug Combination; Whipple Disease

The clinical diagnosis of Lyme borreliosis is easily established in the initial phase of the illness. Erythema chronicum migrans is pathognomonic of this infection. However, during further complications (neurological, cardiac or articular) the diagnosis is chiefly based on laboratory results. The detection of specific antibodies to B. burgdorferi is one of the effective means of confirming the diagnosis. Culture or isolation of this bacteria is not routinely performed due to its very low yield. In this article a case of serologically proved neuro-borreliosis is described and the methods of diagnosis are discussed. Intrathecal synthesis of antibodies observed in the cerebrospinal fluid of this patient and the specificity of serologic tests confirmed by Western-blot provide the diagnosis. However, the absence of locally synthesized antibodies in the cerebrospinal fluid is not sufficient to rule out neuro-borreliosis.

Topics: Aged; Antibodies, Bacterial; Blotting, Western; Borrelia burgdorferi Group; Ceftriaxone; Central Nervous System Diseases; Humans; Lyme Disease; Male