ro13-9904 and Cognition-Disorders

Lyme disease (Lyme borreliosis) is caused by the tick-borne spirochete Borrelia burgdorferi. Long-term persistent illness following antibiotic treatment is not uncommon, particularly when treatment is delayed. Current treatment guidelines for persistent disease primarily rely on findings from four randomized, controlled trials (RCTs), strongly advising against retreatment.. We performed a biostatistical review of all published RCTs evaluating antibiotic retreatment, focusing on trial design, analysis and conclusions.. Four RCTs met the inclusion criteria; all examined the efficacy of intravenous ceftriaxone versus placebo at approximately 3 or 6 months. Design assumptions for the primary outcomes in the two Klempner trials and two outcomes in the Krupp trial were unrealistic and the trials were likely underpowered to detect clinically meaningful treatment effects. The Klempner trials were analyzed using inefficient statistical methods. The Krupp RCT was well-designed and analyzed for fatigue, finding statistically significant and clinically meaningful improvement. Fallon corroborated this finding. Fallon also found improvement in cognitive functioning, a primary outcome, at 12 weeks which was not sustained at 24 weeks; improvements in physical functioning and pain were demonstrated at week 24 as an interaction effect between treatment and baseline symptom severity with the drug effect increasing with higher baseline impairment.. This biostatistical review reveals that retreatment can be beneficial. Primary outcomes originally reported as statistically insignificant were likely underpowered. The positive treatment effects of ceftriaxone are encouraging and consistent with continued infection, a hypothesis deserving additional study. Additional studies of persistent infection and antibiotic treatment are warranted.

Topics: Administration, Intravenous; Anti-Bacterial Agents; Ceftriaxone; Chronic Disease; Cognition Disorders; Fatigue; Humans; Lyme Disease; Randomized Controlled Trials as Topic; Retreatment

Following antibiotic treatment for Lyme disease, some patients report persistent or relapsing symptoms of pain, fatigue, and/or cognitive deficits. Factors other than active infection, including immune abnormalities, have been suggested, but few clues regarding mechanism have emerged. Furthermore, the effect of antibiotic treatment on immune response in affected individuals remains unknown. In this study, a longitudinal analysis of specific immune markers of interest was carried out in patients with a history of Lyme disease and persistent objective memory impairment, prior to and following treatment with either ceftriaxone or placebo. IFNα activity was measured by detection of serum-induced changes in specific target genes, using a functional cell-based assay and quantitative real-time PCR. Level and pattern of antibody reactivity to brain antigens and to Borrelia burgdorferi proteins were analyzed by ELISA and immunoblotting. Sera from the patient cohort induced significantly higher expression of IFIT1 and IFI44 target genes than those from healthy controls, indicating increased IFNα activity. Antibody reactivity to specific brain and borrelial proteins was significantly elevated in affected patients. IFNα activity and antibody profile did not change significantly in response to ceftriaxone. The heightened antibody response implies enhanced immune stimulation, possibly due to prolonged exposure to the organism prior to the initial diagnosis and antibiotic treatment of Lyme disease. The increase in IFNα activity is suggestive of a mechanism contributing to the ongoing neuropsychiatric symptoms.

Topics: Adult; Antibodies, Bacterial; Borrelia burgdorferi; Ceftriaxone; Chronic Disease; Cognition Disorders; Female; Humans; Interferon-alpha; Lyme Disease; Male; Middle Aged

Optimal treatment remains uncertain for patients with cognitive impairment that persists or returns after standard IV antibiotic therapy for Lyme disease.. Patients had well-documented Lyme disease, with at least 3 weeks of prior IV antibiotics, current positive IgG Western blot, and objective memory impairment. Healthy individuals served as controls for practice effects. Patients were randomly assigned to 10 weeks of double-masked treatment with IV ceftriaxone or IV placebo and then no antibiotic therapy. The primary outcome was neurocognitive performance at week 12-specifically, memory. Durability of benefit was evaluated at week 24. Group differences were estimated according to longitudinal mixed-effects models.. After screening 3368 patients and 305 volunteers, 37 patients and 20 healthy individuals enrolled. Enrolled patients had mild to moderate cognitive impairment and marked levels of fatigue, pain, and impaired physical functioning. Across six cognitive domains, a significant treatment-by-time interaction favored the antibiotic-treated group at week 12. The improvement was generalized (not specific to domain) and moderate in magnitude, but it was not sustained to week 24. On secondary outcome, patients with more severe fatigue, pain, and impaired physical functioning who received antibiotics were improved at week 12, and this was sustained to week 24 for pain and physical functioning. Adverse events from either the study medication or the PICC line were noted among 6 of 23 (26.1%) patients given IV ceftriaxone and among 1 of 14 (7.1%) patients given IV placebo; these resolved without permanent injury.. IV ceftriaxone therapy results in short-term cognitive improvement for patients with posttreatment Lyme encephalopathy, but relapse in cognition occurs after the antibiotic is discontinued. Treatment strategies that result in sustained cognitive improvement are needed.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Arthralgia; Brain; Ceftriaxone; Cognition Disorders; Double-Blind Method; Drug Administration Schedule; Female; Humans; Injections, Intravenous; Lyme Neuroborreliosis; Male; Middle Aged; Neuropsychological Tests; Placebo Effect; Placebos; Recurrence; Time; Treatment Outcome

It is controversial whether additional antibiotic treatment will improve cognitive function in patients with post-treatment chronic Lyme disease (PTCLD).. To determine whether antibiotic therapy improves cognitive function in two randomized double-blind placebo-controlled studies of patients with PTCLD.. A total of 129 patients with a physician-documented history of Lyme disease from three study sites in the northeast United States were studied. Seventy-eight were seropositive for IgG antibodies against Borrelia burgdorferi, and 51 were seronegative. Patients in each group were randomly assigned to receive IV ceftriaxone 2 g daily for 30 days followed by oral doxycycline 200 mg daily for 60 days or matching IV and oral placebos. Assessments were made at 90 and 180 days after treatment. Symptom severity was measured from the cognitive functioning, pain, and role functioning scales of the Medical Outcomes Study (MOS). Memory, attention, and executive functioning were assessed using objective tests. Mood was assessed using the Beck Depression Inventory and Minnesota Multiphasic Personality Inventory.. There were no significant baseline differences between seropositive and seronegative groups. Both groups reported a high frequency of MOS symptoms, depression, and somatic complaints but had normal baseline neuropsychological test scores. The combined groups showed significant decreases in MOS symptoms, higher objective test scores, and improved mood between baseline and 90 days. However, there were no significant differences between those receiving antibiotics and placebo.. Patients with post-treatment chronic Lyme disease who have symptoms but show no evidence of persisting Borrelia infection do not show objective evidence of cognitive impairment. Additional antibiotic therapy was not more beneficial than administering placebo.

Topics: Administration, Oral; Affect; Aged; Ceftriaxone; Chronic Disease; Cognition Disorders; Depression; Double-Blind Method; Doxycycline; Drug Therapy, Combination; Female; Humans; Infusions, Intravenous; Lyme Neuroborreliosis; Male; Middle Aged; Neuropsychological Tests; Pain; Sensation Disorders; Treatment Failure

To determine whether post Lyme syndrome (PLS) is antibiotic responsive.. The authors conducted a single-center randomized double-masked placebo-controlled trial on 55 patients with Lyme disease with persistent severe fatigue at least 6 or more months after antibiotic therapy. Patients were randomly assigned to receive 28 days of IV ceftriaxone or placebo. The primary clinical outcomes were improvement in fatigue, defined by a change of 0.7 points or more on an 11-item fatigue questionnaire, and improvement in cognitive function (mental speed), defined by a change of 25% or more on a test of reaction time. The primary laboratory outcome was an experimental measure of CSF infection, outer surface protein A (OspA). Outcome data were collected at the 6-month visit.. Patients assigned to ceftriaxone showed improvement in disabling fatigue compared to the placebo group (rate ratio, 3.5; 95% CI, 1.50 to 8.03; p = 0.001). No beneficial treatment effect was observed for cognitive function or the laboratory measure of persistent infection. Four patients, three of whom were on placebo, had adverse events associated with treatment, which required hospitalization.. Ceftriaxone therapy in patients with PLS with severe fatigue was associated with an improvement in fatigue but not with cognitive function or an experimental laboratory measure of infection in this study. Because fatigue (a nonspecific symptom) was the only outcome that improved and because treatment was associated with adverse events, this study does not support the use of additional antibiotic therapy with parenteral ceftriaxone in post-treatment, persistently fatigued patients with PLS.

Topics: Adult; Aged; Antigens, Bacterial; Antigens, Surface; Bacterial Outer Membrane Proteins; Bacterial Vaccines; Borrelia burgdorferi; Ceftriaxone; Chronic Disease; Cognition Disorders; Double-Blind Method; Fatigue; Female; Humans; Lipoproteins; Lyme Disease; Lyme Neuroborreliosis; Male; Middle Aged; Neuropsychological Tests; Pain; Psychomotor Performance; Severity of Illness Index; Treatment Outcome

The complement C1q plays a critical role in microglial phagocytosis of glutamatergic synapses and in the pathogenesis of neuroinflammation in Alzheimer's disease (AD). We recently reported that upregulation of metabotropic glutamate receptor signaling is associated with increased synaptic C1q production and subsequent microglial phagocytosis of synapses in the rodent models of AD. Here, we explored the role of astrocytic glutamate transporter in the synaptic C1q production and microglial phagocytosis of hippocampal glutamatergic synapses in a rat model of AD. Activation of astrocyte and reduction glutamate transporter 1 (GLT1) were noted after bilateral microinjection of amyloid-beta (Aβ

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Aspartic Acid; Astrocytes; CA1 Region, Hippocampal; Ceftriaxone; Cognition Disorders; Complement C1q; Disease Models, Animal; Excitatory Amino Acid Transporter 2; Glutamic Acid; Male; Microglia; Morris Water Maze Test; Neurons; Patch-Clamp Techniques; Peptide Fragments; Phagocytosis; Rats; Rats, Sprague-Dawley; Receptors, Glutamate; Synapses; Up-Regulation

Whipple disease is a rare, chronic multisystem infectious disease. The central nervous system (CNS) is secondarily involved in 43% of patients; 5% of patients have isolated or primary CNS involvement. The most frequent CNS symptoms are cognitive changes. Prosopagnosia is an inability to recognize familiar faces, in a person who does not have vision impairments or cognitive alterations. This relatively rare condition is usually related to vascular, traumatic, degenerative, or infectious lesions. We report a 54-year-old woman who presented subacutely with fever, headache, and seizures that led to a diagnosis of infectious meningoencephalitis. She improved temporarily on broad-spectrum antibiotics, but then developed a chronically evolving cognitive impairment with associative prosopagnosia as the major complaint. She had a history of sporadic abdominal pain and mild sacroiliac arthralgia. After a negative duodenal biopsy, we confirmed primary CNS Whipple disease by polymerase chain reaction and brain biopsy. We treated the patient with ceftriaxone for 15 days and then co-trimoxazole for 2 years. At 8-year follow-up, she had no further impairments, but continuing prosopagnosia. To our knowledge, this is the first description of isolated prosopagnosia in a patient with primary CNS Whipple disease. Because CNS Whipple disease can lead to serious, irreversible lesions if not promptly treated, clinicians must suspect the diagnosis, treat with long-term antibiotics, and follow patients carefully to prevent recurrence.

Topics: Anti-Bacterial Agents; Ceftriaxone; Cognition Disorders; Female; Humans; Middle Aged; Prosopagnosia; Whipple Disease

Despite the development of new antibiotic agents, mortality of pneumococcal meningitis remains high. In addition, meningitis results in severe long-term morbidity, most prominently cognitive deficits. Granulocyte colony-stimulating factor (G-CSF) stimulates proliferation and differentiation of hematopoietic progenitor cells and increases the number of circulating neutrophil granulocytes. This study investigated the effect of adjuvant G-CSF treatment on cognitive function after pneumococcal meningitis. C57BL/6 mice were infected by subarachnoid injection of Streptococcus pneumoniae serotype 3 and treated with ceftriaxone and G-CSF subcutaneously or ceftriaxone alone for 5 days. Clinical scores, motor performance, and mortality during bacterial meningitis were unaffected by adjuvant G-CSF treatment. No effect of G-CSF treatment on production of proinflammatory cytokines or activation of microglia or astrocytes was observed. The G-CSF treatment did, however, result in hippocampal neurogenesis and improved spatial learning performance 6 weeks after meningitis. These results suggest that G-CSF might offer a new adjuvant therapeutic approach in bacterial meningitis to reduce long-term cognitive deficits.

Topics: Adult Stem Cells; Animals; Anti-Bacterial Agents; Ceftriaxone; Cell Differentiation; Cognition Disorders; Cytokines; Disease Models, Animal; Granulocyte Colony-Stimulating Factor; Hippocampus; Male; Maze Learning; Meningitis, Pneumococcal; Mice; Mice, Inbred C57BL; Motor Activity; Neurogenesis; Phosphorylation; Streptococcus pneumoniae; Time Factors

Multiple lines of investigation have explored the role of glutamatergic and purinergic systems in epilepsy, related cognitive impairment, and oxidative stress. Glutamate transporters, particularly GLT-1 expression, were found to be decreased, and purinergic receptor, P2X7 expression, was found to be increased in brain tissue associated with epilepsy. The present study was carried out to investigate the effect of ceftriaxone (GLT-1 upregulator) and Brilliant Blue G (P2X7 antagonist) against PTZ-induced kindling in rats. The study was further extended to elucidate the cross-link between glutamatergic and purinergic pathways in epilepsy.. Systemic administration of subconvulsant dose of PTZ (30 mg/kg) every other day for 27days (14 injections) significantly increased the mean kindling, and developed generalized tonic-clonic seizures, and reduced motor co-ordination, cognitive skills, oxidative defense (increases lipid peroxidation, nitrite levels and decreases GSH level) and acetylcholinesterase enzyme activities in the cortex and subcortical region. Treatments with CEF (100 and 200mg/kg) and BBG (15 and 30 mg/kg) alone and in combination (CEF 100mg/kg and BBG 15 mg/kg) significantly decreased the mean kindling score and restored behavioral and oxidative defense activities compared with treatment with PTZ.. The combination of both the drugs was shown to have better effect in preventing kindled seizures and a significantly synergistic effect compared with their effect alone in PTZ-kindled rats. The present study elucidated the mechanistic role of GLT-1 modulator and selective P2X7 antagonist and their combination against PTZ-induced kindling. The study for the first time demonstrated the cross-link between glutamatergic and purinergic pathways in epilepsy treatment.

Topics: Animals; Brain; Ceftriaxone; Cognition Disorders; Convulsants; Dose-Response Relationship, Drug; Epilepsy; Excitatory Amino Acid Transporter 2; Kindling, Neurologic; Lipid Peroxidation; Male; Oxidative Stress; Pentylenetetrazole; Purinergic P2X Receptor Antagonists; Rats; Rosaniline Dyes; Seizures

We herein report a heterosexual Japanese man in his forties who had been suffering from advanced dementia and personality change for 4 years. Positive results of a serological test for syphilis, Treponema pallidum hemagglutination assay, and fluorescent treponemal antibody-absorption test of both serum and cerebral spinal fluid led to the diagnosis of neurosyphilis. Jarisch-Herxheimer reaction was seen shortly after the first dose of penicillin was administered to the patient. His cognitive function did not recover after treatment. The incidence of syphilis has been reported to be increasing. Neurosyphilis should not be overlooked as an etiology for progressive dementia even in this post-antibiotic era.

Topics: Adult; Anti-Bacterial Agents; Antibodies, Bacterial; Ceftriaxone; Cognition Disorders; Dementia; Hemagglutination Tests; Humans; Incidence; Male; Mental Disorders; Neurosyphilis; Penicillin G; Treponema pallidum

Traumatic brain injury (TBI) is a leading cause of mortality and disability in children and young adults worldwide. Neurologic impairment is caused by both immediate brain tissue disruption and post-injury cellular and molecular events that worsen the primary neurologic insult. The β-lactam antibiotic ceftriaxone (CTX) has been reported to induce neuroprotection in animal models of diverse neurologic diseases via up-regulation of GLT-1. However, no studies have addressed the neuroprotective role of CTX in the setting of TBI, and whether the mechanism is involved in the modulation of neuronal autophagy remains totally unclear. The present study was designed to determine the hypothesis that administration of CTX could significantly enhance functional recovery in a rat model of TBI and whether CTX treatment could up-regulate GLT-1 expression and suppress post-TBI neuronal autophagy. The results demonstrated that daily treatment with CTX attenuated TBI-induced brain edema and cognitive function deficits in rats. GLT-1 is down-regulated following TBI and this phenomenon can be reversed by treatment of CTX. In addition, we also found that CTX significantly reduced autophagy marker protein, LC3 II, in hippocampus compared to the TBI group. These results suggest that CTX might provide a new therapeutic strategy for TBI and this protection might be associated with up-regulation of GLT-1 and suppression of neuronal autophagy.

Topics: Animals; Autophagy; Brain Edema; Brain Injuries; Ceftriaxone; Cognition Disorders; Disease Models, Animal; Excitatory Amino Acid Transporter 2; Hippocampus; Male; Maze Learning; Microtubule-Associated Proteins; Neuroprotective Agents; Random Allocation; Rats, Sprague-Dawley; Recovery of Function; Up-Regulation

Topics: Anti-Bacterial Agents; Borrelia burgdorferi; Ceftriaxone; Cognition Disorders; Fatigue; Female; Humans; Lipoproteins; Lyme Disease; Lyme Neuroborreliosis; Male

Pneumococcal meningitis often results in death or neurological sequelae, but the underlying pathogenetic mechanisms remain poorly understood. In C57BL/6J mice subjected to intracerebroventricular (icv) challenge with Streptococcus pneumoniae, the chemokine CCL2 and cytokines interferon-γ, interleukin (IL)-1β, IL-6 and tumour necrosis factor were prominently expressed in the brain during the acute phase of the disease. The upregulation of these immune mediators was markedly diminished in IL-18-deficient mice. Uninfected IL-18(-/-) mice exhibited decreases in anxiety phenotype and licking behaviour, and an increase in behavioural habituation, in an automated monitoring system (the IntelliCage). Without antibiotic intervention, a majority of IL-18(+/+) mice developed irreversible disease after icv S. pneumoniae but this was significantly improved by deleting IL-18 gene function. IL-18(+/+) mice cured of pneumococcal meningitis with four doses of ceftriaxone, initiated at 20 h post-inoculation, showed enduring sequelae. These included abnormal behavioural phenotypes featuring diurnal hypoactivity and nocturnal hyperactivity, light phobia and disrupted cognitive function. While the hyperactive phenotype was absent in the corresponding IL-18(-/-) survivors, cognitive impairments and behavioural deficits were still present. Overall, the results suggest that the high levels of cytokines and/or chemokines released after pneumococcal challenge provoked a series of pathological events, ultimately causing acute death. Furthermore, since only a subset of behavioural phenotypes were ameliorated in the pneumococcus-infected IL-18(-/-) mice, the pathological pathways causing mortality may be, at least in part, distinct from those leading to long-term neurological sequelae.

Topics: Animals; Anti-Bacterial Agents; Anxiety; Ceftriaxone; Chemokines; Circadian Rhythm; Cognition Disorders; Cytokines; Disease Models, Animal; Disease Progression; Drinking Behavior; Exploratory Behavior; Female; Habituation, Psychophysiologic; Interleukin-18; Meningitis, Pneumococcal; Mice; Mice, Inbred C57BL; Mice, Knockout; Motor Activity; Photic Stimulation

Early brain injury (EBI) after subarachnoid hemorrhage (SAH) is characterized by a reduction in excitatory amino acid transporter 2 (EAAT2) expression and severe amino acid excitotoxicity. The aim of this study was to explore the neuroprotective effect of ceftriaxone (CEF), a potent compound that up-regulates EAAT2, against EBI and the potential mechanisms using in vitro experiments and a rat model of SAH. Intracisternal treatment with CEF significantly improved neurological outcomes and alleviated extracellular glutamate accumulation after SAH. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) staining and Western blot analysis of cleaved caspase 3 showed that CEF decreased hippocampal neuronal apoptosis following SAH. Immunofluorescent staining and Western blotting revealed that CEF significantly reversed the down-regulation of EAAT2 expression following SAH. In Morris water maze (MWM) tests, CEF remarkably ameliorated the SAH-induced cognitive dysfunction in spatial learning memory and reference memory. CEF promoted the nuclear translocation of p65 as well as the activation of Akt in hippocampal astrocytes in vitro and in vivo. These findings suggest that CEF may exert significant protective effects against EBI following SAH by modulating the PI3K/Akt/NF-κB signaling pathway.

Topics: Animals; Apoptosis; Astrocytes; Brain Injuries; Caspase 3; Ceftriaxone; Cells, Cultured; Cognition Disorders; Disease Models, Animal; Excitatory Amino Acid Transporter 2; Glutamic Acid; Hippocampus; Male; Neoplasm Proteins; Neurons; Neuroprotective Agents; NF-kappa B; Nucleocytoplasmic Transport Proteins; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Rats, Sprague-Dawley; Signal Transduction; Subarachnoid Hemorrhage

Young-onset dementias pose a major challenge to both clinicians and researchers. Cognitive decline may be accompanied by systemic features, leading to a diagnosis of "dementia plus" syndromes. Whipple disease is a rare systemic illness characterized by arthralgias, chronic diarrhea, weight loss, fever, and abdominal pain. Central nervous system involvement, including severe cognitive deterioration, may precede systemic manifestations, appear during the course of the disease, or even be the only symptom. We report a previously highly functional 48-year-old man whom we first suspected of having early-onset neurodegenerative dementia but then diagnosed with Whipple disease based on a detailed clinical and laboratory evaluation. Initial neuropsychological evaluation revealed marked impairment in the patient's fluid intelligence and severe cognitive deficits in his information processing speed, complex attention, memory, visuomotor and construction dexterities, problem solving, and executive functions. At neuropsychological follow-up 21 months later, his information processing speed had improved only slightly and deficits persisted in his other cognitive functions. Repeat brain magnetic resonance imaging at that time showed that he had responded to antibiotic treatment. Because Whipple disease can cause young-onset "dementia plus" syndromes that may leave patients with neurocognitive deficits even after apparently successful treatment, we recommend comprehensive neuropsychological assessment for early detection of residual and reversible cognitive processes and evaluation of treatment response.

Topics: Anti-Bacterial Agents; Brain; Ceftriaxone; Cognition; Cognition Disorders; Diagnosis, Differential; Humans; Infusions, Intravenous; Magnetic Resonance Imaging; Male; Memory Disorders; Middle Aged; Neurodegenerative Diseases; Neuropsychological Tests; Treatment Outcome; Whipple Disease

Hyperactivity of the glutamatergic system is involved in excitotoxicity and neurodegeneration in Parkinson's disease (PD) and treatment with drugs modulating glutamatergic activity may have beneficial effects. Ceftriaxone has been reported to increase glutamate uptake by increasing glutamate transporter expression. The aim of this study was to determine the effects of ceftriaxone on working memory, object recognition, and neurodegeneration in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD rat model. MPTP was stereotaxically injected into the substantia nigra pars compacta (SNc) of male Wistar rats. Then, starting the next day (day 1), the rats were injected daily with either ceftriaxone (200 mg/kg/day, i.p.) or saline for 14 days and underwent a T-maze test on days 8-10 and an object recognition test on days 12-14. MPTP-lesioned rats showed impairments of working memory in the T-maze test and of recognition function in the object recognition test. The treatment of ceftriaxone decreased the above MPTP-induced cognitive deficits. Furthermore, this study provides evidence that ceftriaxone inhibits MPTP lesion-induced dopaminergic degeneration in the nigrostriatal system, microglial activation in the SNc, and cell loss in the hippocampal CA1 area. In conclusion, these data support the idea that hyperactivity of the glutamatergic system is involved in the pathophysiology of PD and suggest that ceftriaxone may be a promising pharmacological tool for the development of new treatments for the dementia associated with PD.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Antiparkinson Agents; Brain; CA1 Region, Hippocampal; Ceftriaxone; Cell Death; Cognition Disorders; Corpus Striatum; Male; Maze Learning; Memory, Short-Term; Microglia; Parkinsonian Disorders; Pars Compacta; Pyramidal Cells; Rats, Wistar; Recognition, Psychology

Topics: Aged; Anti-Bacterial Agents; Anticonvulsants; Borrelia burgdorferi; Ceftriaxone; Cognition Disorders; Epilepsy, Temporal Lobe; Female; Hemianopsia; Humans; Lyme Neuroborreliosis; Neurotoxicity Syndromes; Valproic Acid

The most frequent clinical manifestation of borreliosis in Switzerland is erythema migrans, with about 2500 patients each year. Neurological manifestations are rare, mostly hyperalgesic radiculitis (Bannwarth syndrome), aseptic meningitis or cranial nerve involvement. We report the first Swiss patient with meningovasculitis due to neuroborreliosis, with recurrent multiple ischemic strokes in multiple vascular territories. The treatment with ceftriaxone stopped the progression, but the patient is still suffering from severe invalidating cognitive disorders. We also comment on the pathophysiology and review the literature of other clinical cases.

Topics: Anti-Infective Agents; Blotting, Western; Borrelia burgdorferi Group; Brain Ischemia; Ceftriaxone; Cognition Disorders; Humans; Lyme Neuroborreliosis; Magnetic Resonance Imaging; Male; Meningitis; Middle Aged; Stroke; Vasculitis, Central Nervous System

Topics: Aged; Anti-Bacterial Agents; Antibodies, Bacterial; Borrelia burgdorferi; Ceftriaxone; Cognition Disorders; Confusion; Diagnosis, Differential; Disease Progression; Erythema Chronicum Migrans; Humans; Inappropriate ADH Syndrome; Lyme Neuroborreliosis; Male; Neurologic Examination; Serologic Tests; Treatment Outcome; Tremor

Topics: Anti-Bacterial Agents; Ceftriaxone; Chronic Disease; Clinical Trials as Topic; Cognition Disorders; Data Interpretation, Statistical; Drug Administration Schedule; Humans; Lyme Neuroborreliosis; Pain; Placebo Effect; Risk Assessment; Time; Treatment Failure

Topics: Ceftriaxone; Chronic Disease; Cognition Disorders; Convalescence; Double-Blind Method; Doxycycline; Drug Evaluation; Fatigue; Humans; Lyme Neuroborreliosis; Pain; Sleep Wake Disorders; Treatment Outcome

We report about a 57-year-old patient suffering from the typical symptoms of normal-pressure hydrocephalus (NPH) including gait disturbance, urinary incontinence, and mental deterioration. CSF analysis established the diagnosis of chronic active Lyme neuroborreliosis with lymphocytic pleocytosis and intrathecal Borrelia burgdorferi antibody production. After several weeks of i.v. antibiotic treatment we observed normalization of CSF parameters as well as a clear improvement of clinical symptoms so that surgical shunting was no longer indicated. Interference with subarachnoid CSF flow may be a possible cause of the observed symptomatic NPH in a patient with chronic Lyme neuroborreliosis.

Topics: Borrelia burgdorferi Group; Brain; Ceftriaxone; Cerebral Ventricles; Chronic Disease; Cognition Disorders; Female; Gait; Humans; Hydrocephalus, Normal Pressure; Lyme Disease; Magnetic Resonance Imaging; Middle Aged; Tomography, Emission-Computed, Single-Photon; Treatment Outcome; Urinary Incontinence

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