JJ Halperin's publications on nervous system Lyme disease (1987-2015)....
Curr Infect Dis Rep. 2015 Jan;17(1):445.
Nervous System Lyme Disease.
Department of Neurosciences, Overlook Medical Center & Atlantic Neurosciences Institute, Icahn School of Medicine at Mount Sinai, 99 Beauvoir Avenue, Summit, NJ, 07902, USA, john.halperin@atlantichealth.org.
Abstract
Lyme disease, a multisystem spirochetal infection, continues to be the subject of considerable debate, but not controversy. Recent years have seen improvements in diagnostic tools, better understanding of pathophysiology, and increasing evidence of efficacy of standard treatment regimens. Nervous system involvement is particularly confusing to patients and many physicians.
A rational approach based on objective findings can clarify the cause and dictate the best treatment of patients' difficulties. Diagnosis for all but the earliest cases rests on the combination of likely contact with infected Ixodes ticks and laboratory confirmation of exposure to the causative organism, Borrelia burgdorferi (two-tier serology, combining ELISA with a confirmatory Western blot). Treatment is generally with oral antimicrobials such as doxycycline. Parenteral regimens are usually necessary only for the most severe cases.
PMID:
25421861
[PubMed - as supplied by publisher]
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Rev Neurol Dis. 2009 Winter;6(1):4-12.
Nervous system lyme disease: diagnosis and treatment.
Department of Neurosciences, Atlantic Neuroscience Institute, Summit, NJ, USA.
Abstract
Lyme disease, the multisystem infectious disease caused by the tickborne spirochete Borrelia burgdorferi, frequently affects the peripheral and central nervous systems. The earliest indication of Lyme disease infection is usually erythema migrans. This large, typically macular erythema, often with a target-like pattern of concentric pale and red circles, gradually enlarges day by day, potentially reaching many centimeters in diameter. In a significant proportion of infected individuals, an acute disseminated phase leads to seeding elsewhere in the body. Up to 5% of patients develop cardiac involvement. In about 10% to 15% of patients, the nervous system becomes symptomatically involved. Current serologic diagnostic tools are quite useful, and standard treatment regimens are highly effective. Oral antimicrobials have been shown to be effective in European neuroborreliosis and presumably are equally potent in North American patients. Long-term antibiotic treatment does not provide any additional lasting improvement, but it is frequently associated with significant morbidity.
PMID:
19367218
[PubMed - indexed for MEDLINE]
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Infect Dis Clin North Am. 2008 Jun;22(2):261-74, vi. doi: 10.1016/j.idc.2007.12.009.
Nervous system Lyme disease.
Department of Neurosciences, Atlantic Neuroscience Institute & Overlook Hospital, Summit, NJ 07902, USA. john.halperin@atlantichealth.org
Abstract
Lyme disease affects the nervous system in about 10% to 15% of infected individuals, most commonly causing lymphocytic meningitis. Cranial neuropathies, particularly facial nerve palsy, also occur frequently. Figuring prominently in the European literature, but less emphasized in the United States, is painful radiculitis, radicular pain involving a limb or trunk dermatome. Treatment of neuroborreliosis is usually straightforward; oral antibiotics may suffice in many patients. In severe cases, 2 to 4 weeks of parenteral therapy is necessary. All available evidence indicates that treatment of more than 4 weeks' duration carries substantial risk but minimal if any additional benefit.
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Neurology. 2007 Jul 3;69(1):91-102. Epub 2007 May 23.
Practice parameter: treatment of nervous system Lyme disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology.
Halperin JJ1, Shapiro ED, Logigian E, Belman AL, Dotevall L, Wormser GP, Krupp L, Gronseth G, Bever CT Jr; Quality Standards Subcommittee of the American Academy of Neurology.
1Department of Neurosciences, Overlook Hospital, NYU School of Medicine, Summit, NJ, USA.
Erratum in
Neurology. 2008 Apr 1;70(14):1223.
Abstract
OBJECTIVE:
To provide evidence-based recommendations on the treatment of nervous system Lyme disease and post-Lymesyndrome. 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 (1983-2003) 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 (> or =8 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).
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Curr Neurol Neurosci Rep. 2005 Nov;5(6):446-52.
Central nervous system Lyme disease.
Department of Neurology, North Shore University Hospital, Manhasset, NY 11030, USA. halperin@nshs.edu
Abstract
Nervous system infection with Borrelia burgdorferi frequently causes meningitis and rarely causes encephalomyelitis. Altered cognitive function also can occur in the absence of central nervous system infection. Recently developed serodiagnostic tools, such as the C6 assay, and appropriate use of Western blotting promise to improve diagnostic accuracy. Treatment trials have demonstrated the efficacy of relatively brief courses of oral antimicrobial agents, even in peripheral nervous system infection and meningitis. Several well-performed studies have clearly shown that prolonged antimicrobial treatment of "post-Lyme disease" is ineffective. Diagnosis and treatment of Lyme disease continue to improve.
PMID:
16263055
[PubMed - indexed for MEDLINE]
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Neurocrit Care. 2006;4(3):260-6.
Is neuroborreliosis a medical emergency?
NYU School of Medicine, Great Neck, NY, USA. Halperin@LINeuro.com
Abstract
Although Lyme disease affects the nervous system in many ways (collectively known as neuroborreliosis), only rarely does it present as a medical emergency. In extreme cases, it may cause (1) encephalitis, (2) a rapidly progressive peripheral neuropathy, or (3) a painful truncal radiculopathy that may be confused with a severe visceral process. Knowing when to consider this spirochetosis in the differential diagnosis requires an understanding of its true clinical spectrum, and of an appropriate diagnostic and therapeutic approach.
PMID:
16757836
[PubMed - indexed for MEDLINE]
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Curr Infect Dis Rep. 2004 Aug;6(4):298-304.
Central Nervous System Lyme Disease.
Abstract
Nervous system infection with Borrelia burgdorferi frequently causes meningitis and rarely causes encephalomyelitis. Altered cognitive function also can occur in the absence of central nervous system infection. Recently developed serodiagnostic tools, such as the C6 assay, and appropriate use of Western blotting, promise to improve diagnostic accuracy. Treatment trials have demonstrated the efficacy of relatively brief courses of oral antimicrobial agents, even in peripheral nervous system infection and meningitis. Several well-performed studies have clearly shown that prolonged antimicrobial treatment of "post-Lyme disease" is ineffective. Diagnosis and treatment of Lyme disease continue to improve.
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Muscle Nerve. 2003 Aug;28(2):133-43.
Lyme disease and the peripheral nervous system.
Department of Neurology, North Shore University Hospital, 300 Community Drive, Manhasset, New York 11030, USA. halperin@nshs.edu
Abstract
Lyme disease, the multisystem infectious disease caused by the tick-borne spirochete Borrelia burgdorferi, causes a broad variety of peripheral nerve disorders, including single or multiple cranial neuropathies, painful radiculopathies, and diffuse polyneuropathies. Virtually all appear to be varying manifestations of a mononeuropathy multiplex. Diagnosis requires that the patient should have had possible exposure to the only known vectors, Ixodes ticks, and also have either other pathognomonic clinical manifestations or laboratory evidence of exposure. Treatment with antimicrobial regimens is highly effective. The mechanism underlying these neuropathies remains unclear, although interactions between anti-Borrelia antibodies and several peripheral nerve constituent molecules raise intriguing possibilities.
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Vector Borne Zoonotic Dis. 2002 Winter;2(4):241-7.
Nervous system Lyme disease.
NYU School of Medicine, New York, New York, USA. halperin@nshs.edu
Abstract
Nervous system involvement in Lyme borreliosis is a much-feared, often-misunderstood disorder. Both the peripheral and central nervous systems may be involved, typically in a multifocal, patchy fashion, perhaps suggesting a vasocentric mechanism. Clinical manifestations vary widely, depending on the site and severity of involvement. Although neurologic manifestations observed in Europe differ somewhat from those reported in the United States, there are also striking similarities, permitting some generalization of information obtained in each population. In general, diagnosis of neurologic disease requires objective evidence of nervous system damage, and must be differentiated from both psychiatric disorders and metabolic encephalopathies, both of which typically occur in the absence of significant neurologic damage or infection. Laboratory confirmation of nervous system involvement by Borrelia burgdorferi has limitations. However, neurophysiologic testing of the peripheral nervous system, imaging of the neuraxis, and examination of the cerebrospinal fluid can all be informative. In contrast, to date functional brain imaging has been of limited specificity. Treatment with one of several straightforward antimicrobial regimens, typically 2-4 weeks in duration, generally results in microbiologic cure. Although some symptoms may persist after this, the data do not suggest that these are responsive to further antimicrobial therapy.
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Curr Treat Options Neurol. 1999 May;1(2):139-146.
Neuroborreliosis (Nervous System Lyme Disease).
North Shore University Hospital, 300 Community Drive, Manhasset, NY 11030, USA.
Abstract
Treatment of nervous system Lyme disease depends on the severity and site of involvement. Although some data indicate that uncomplicated Lyme meningitis can be treated effectively with oral doxycycline, central nervous system infection (meningitis, radiculitis, encephalomyelitis, and cranial neuritis) is usually treated with parenteral antibiotics for 14 to 30 days, depending on disease severity, as is severe and progressive peripheral nervous system involvement. Ceftriaxone, 2 g/d, is the most commonly used regimen; cefotaxime, 2 g every 8 hours, appears to be equally effective. Penicillin in meningeal doses is also effective, perhaps slightly less so than the third-generation cephalosporins, but it is less convenient to administer. For patients with prohibitive drug allergies, treatment with oral doxycycline in doses of 300 to 400 mg/d may be effective. In patients with facial palsy or with indolent peripheral neuropathies, a trial of oral medication (doxycycline, 100 mg two or three times a day, or amoxicillin, 500 to 1000 mg three times a day for 21 to 30 days) is reasonable. Patients for whom this fails are treated with parenteral medications.
PMID:
11096703
[PubMed - as supplied by publisher]
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J Neurol Sci. 1998 Jan 8;153(2):182-91.
Nervous system Lyme disease.
Department of Neurology, North Shore University Hospital, Manhasset, NY 11030, USA. halperin@nshs.edu
Abstract
Lyme disease is a multisystem infectious disease caused by tick-borne spirochetes of the Borrelia burgdorferi group. The disease occurs primarily in specific areas of North America, Europe and Asia, reflecting the distribution of the hard-shelled Ixodes ticks that are required for disease transmission. Diagnosis of this infection can be somewhat problematic, although in clinically appropriate settings, serologic testing can be highly useful, particularly if Western blots are used to confirm borderline or positive results. The organism has several specific organotropisms-involvement of the heart, joints and nervous system being particularly common. The nervous system can be involved in one or more ways. Early in infection, patients tend to get a lymphocytic meningitis, cranial neuritis (particularly the facial nerves) or a painful radiculitis. Rarely, an encephalomyelitis can occur. In patients with more protracted and indolent involvement, a more disseminated mononeuropathy multiplex may occur, or a mild, non-focal alteration of cognitive function and memory, i.e. an encephalopathy. In patients with central nervous system involvement, the most sensitive diagnostic test is the demonstration of intrathecal production of anti-Borrelia burgdorferi antibody. Culture, polymerase chain reaction and other techniques appear to be less specific. In most instances, the disease is quite responsive to antimicrobial therapy. Oral treatment with doxycycline has been shown to be effective in meningitis. In more serious cases two to four week courses of parenteral ceffriaxone or cefotaxime are effective in the vast majority of patients.
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Scand J Infect Dis Suppl. 1991;77:74-80.
North American Lyme neuroborreliosis.
Department of Neurology, State University of New York, Stony Brook 11794.
Abstract
Clinical, neurophysiologic and laboratory findings obtained in American patients with nervous system Lyme borreliosis were compared to published observations in European neuroborreliosis patients. In both populations, Borrelia burgdorferi infection is commonly associated with neurologic abnormalities. European reports have emphasized dramatic clinical phenomena, such as painful radiculitis (Garin-Bujadoux-Bannwarth syndrome) and chronic progressive spastic paraparesis. North American patients seem to develop milder forms of nervous system involvement. Peripheral nervous system manifestations take a variety of forms, ranging from mild, intermittent sensory symptoms, to typical painful radiculitis. Despite the range of clinical presentations, neurophysiologic and morphologic analyses indicate these all represent different manifestations of the same pathophysiologic process, which, in turn, is similar to what has been described in Garin-Bujadoux-Bannwarth syndrome. Similarly, central nervous system (CNS) symptoms vary widely, ranging from a mild confusional state to a severe encephalitis. The encephalitis is probably due to direct CNS infection. In some instances the confusional state may also be due to CNS infection but it is likely that in many patients it is not. As in European patients, the most reliable indicator of CNS infection appears to be the intrathecal production of anti-B burgdorferi antibodies. Although North American Lyme borreliosis patients may often develop milder forms of nervous system involvement that their European counterparts, there is considerable overlap, and the underlying pathophysiologic mechanisms are probably identical.
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Semin Neurol. 1997 Mar;17(1):19-24.
Neuroborreliosis: central nervous system involvement.
Department of Neurology, North Shore University Hospital, Manhasset, NY 11030, USA.
Abstract
Despite rapid dissemination of Borrelia burgdorferi throughout the body following initial inoculation, the clinical manifestations of this illness tend to involve specific organ systems preferentially. The nervous system, in particular, is frequently affected; involvement usually follows one of several distinct patterns. Most commonly, patients develop a lymphocytic meningitis, radiculoneuritis or cranial neuropathy, occurring singly or in combination. Patients with radicular involvement often have a myelopathic component as well. At the other extreme, rare patients will develop focal inflammation of the central nervous system, an encephalomyelitis, that appears to involve white matter more often than grey. More commonly, patients may develop cognitive and memory impairment-a mild encephalopathy. In some patients this may represent a subtle form of encephalomyelitis, while in others it is probably a "toxic-metabolic" effect of systemic infection. Disease variability among patients probably is the result of multiple factors, including bacterial strain differences in virulence and organotropism, inoculum size, host immunity, and simultaneous co-infection with other tick-borne organisms. Accurate diagnosis remains somewhat problematic. The cerebrospinal fluid is almost always abnormal in the presence of active CNS infection. Intrathecal production of specific antibody can be demonstrated in over 90% of patients with meningitis or frank inflammatory encephalomyelitis; in patients with a milder encephalopathy this is less consistently observed. In most instances, diagnosis relies on a combination of demonstration of a specific immune response, and clinical judgment. In patients in whom the diagnosis is secure, appropriate antimicrobial therapy is highly effective in the vast majority of cases, although if there has been significant structural damage to the CNS, some residua may remain.
PMID:
9166955
[PubMed - indexed for MEDLINE]
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Am J Med. 1995 Apr 24;98(4A):52S-56S; discussion 56S-59S.
Neuroborreliosis.
Department of Neurology, North Shore University Hospital, Manhasset, New York 11030, USA.
Abstract
Lyme disease is a multisystem infectious disease with frequent nervous system involvement. It affects peripheral nerves, the meningeal lining of the central nervous system (CNS), and the CNS parenchyma, but the underlying pathophysiology remains unclear. Considerable data suggest that dividing Lyme neuroborreliosis into early and late disease stages, as has been done with syphilis--the other well-known spirochetosis that affects the nervous system--lacks pathophysiologic validity. Early CNS seeding has been demonstrated, however, and lymphocytic meningitis and facial paralysis tend to occur relatively early in infection, although radiculoneuropathy and cranial neuropathies may also occur later. Less fulminant forms of peripheral nerve or CNS involvement may present later in the disease course. Encephalomyelitis may occur early or late but is rare; encephalopathy is far more common and tends to occur in patients with evidence of systemic (but not necessarily CNS) Lyme disease. Diagnosis of CNS infection has been difficult, and most studies have relied on indirect methods. Demonstration of intrathecal production of anti-Borrelia burgdorferi antibodies provides the strongest evidence, but correction for the amount of peripheral blood immunoreactivity to B. burgdorferi that crosses the blood-brain barrier is essential. Newer technologies have been applied in an effort to improve detection of B. burgdorferi itself--polymerase chain reaction may provide a sensitive tool for organism detection to complement immunologic techniques. The optimal treatment regimen for Lyme disease has not been defined, but a course of ceftriaxone (2 g/day) or cefotaxime (6 g/day) for 3-4 weeks is commonly prescribed. Intravenous penicillin and oral doxycycline (200 mg/day) for 2 weeks have been used successfully to treat Lyme meningitis, but these results require confirmation.
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Arch Neurol. 1992 Jan;49(1):102-7.
Nervous system Lyme borreliosis--revisited [corrected; erratum to be published].
Finkel MF1, Halperin JJ, Finkel MJ.
1Department of Neurology, Midelfort Clinic, Eau Claire, Wis.
Abstract
A great deal of confusion surrounds the diagnosis, clinical phenomenology, and treatment of Lyme borreliosis. Most diagnostic methods currently in use are indirect and do not differentiate between prior exposure and current infection. A critical review of the literature permits the characterization of a distinct set of neurologic disorders that are almost certainly caused by this infection and their differentiation from the plethora of syndromes that have been anecdotally linked to infection, but in which causality has never been established. This article describes the range of clinical disorders associated with Lyme borreliosis, provides an overview of current approaches to diagnosis, and reviews current treatment protocols.
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Rev Infect Dis. 1989 Sep-Oct;11 Suppl 6:S1518-25.
A perspective on the treatment of Lyme borreliosis.
Luft BJ1, Gorevic PD, Halperin JJ, Volkman DJ, Dattwyler RJ.
1Department of Medicine, University of New York, Stony Brook 11794-8153.
Abstract
Lyme borreliosis has become the most common tick-borne infection in the United States. Although both beta-lactam and tetracycline antibiotics have been shown to be effective in the treatment of this spirochetosis, the development of optimal therapeutic modalities has been hampered by the lack of reliable microbiologic or immunologic criteria for the diagnosis or cure of this infection. In vitro sensitivity studies have been performed by several laboratories, but there has been no standardization of the methodology for measuring either inhibitory or bactericidal levels. Clinical studies have documented the efficacy of antibiotics, but therapy has failed in as many as 50% of cases of chronic infection. Although new antibiotic regimens appear promising, the optimal treatment of this infectious disease remains to be determined. In this report we review the clinical and experimental rationale for the antibiotic regimens that we currently use and the need for a more standardized approach to treatment trials.
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Rheum Dis Clin North Am. 1989 Nov;15(4):635-47.
Nervous system manifestations of Lyme disease.
Department of Neurology, State University of New York, Stony Brook.
Abstract
Neurologic involvement is commonplace in Lyme borreliosis. Neuropathies can be acute or chronic, focal or disseminated, but are predominantly axonal. CNS infection can also be acute or indolent, focal or disseminated; meningitis, encephalitis, and cranial nerve palsies occur. A mild encephalopathy is also common, but only occasionally due to CNS infection.
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Arthritis Rheum. 1987 Apr;30(4):448-50.
Failure of tetracycline therapy in early Lyme disease.
Abstract
We describe the clinical courses of 5 patients with Lyme disease who developed significant late complications, despite receiving tetracycline early in the course of their illness. All 5 patients had been treated for erythema chronicum migrans with a course of tetracycline that met or exceeded current recommendations. The late manifestations of Lyme disease included arthritis, cranial nerve palsy, peripheral neuropathy, chronic fatigue, and changes in mental function. Our findings suggest that the use of tetracycline at a dosage of 250 mg, 4 times a day for 10 days, as a treatment for early Lyme disease should be reconsidered. To determine optimal therapy for early Lyme disease, a study that compares an increased dosage of tetracycline with alternative treatments is indicated.
PMID:
3580012
[PubMed - indexed for MEDLINE]