Search

Lyme disease, caused by Borrelia burgdorferi (Bb) infection, has a broad spectrum of clinical manifestations and severity. Patients with possible Lyme disease may seek out or be referred to rheumatologists. Today, the most common reason to engage a rheumatologist is due to complaints of arthralgia. After skin, neurologic manifestations of Lyme disease are now among the most common. Therefore, it is important for rheumatologists to be aware of clues that suggest neurologic Lyme disease and prompt help from a neurologist experienced with Lyme disease.

Objectives: The objective of the Therapy Optimization in MS (TOP MS) Study was to prospectively assess the relationship between MS disease-modifying therapy (DMT) adherence and MS relapse risk over 2 years., Methods: Potential participants were recruited for TOP MS by specialty pharmacies who dispensed glatiramer acetate and beta interferons for MS nationwide. Signed IRB-approved informed consents were returned to the pharmacies. TOP MS used electronic data capture with monthly patient entries. Adherence, measured by medication possession ratio (MPR), was derived from pharmacy shipment records. Logistic regression examined the association between protocol-defined relapses and DMT MPR (<0.5; >0.5-<0.9; >0.9)., Results: TOP MS enrolled 3151 persons with MS, and 2410 completed the full 2 years. Across all therapies, the mean MPR for the 2-year completer cohort of 2049 who maintained the same DMT was 0.9+0.2 (range: 0.1-1.0), with 63.8% reaching a 2-year MPR >0.9. Evaluated by categories of MPR, the proportion of participants remaining relapse-free for 24 months increased with increasing MPR, and the proportion with >1 relapses declined with increasing levels of MPR (p<0.0008). Regression analysis revealed the odds of relapse for a patient in the MPR >0.9 MPR group was 64% that of a patient in the MPR <0.5 category (p=0.02). Use of >1 DMT prior to the current one was an independent predictor of relapse., Conclusions: The study provides class III evidence that improvement in adherence to DMT for MS is associated with improved clinical outcomes as measured by relapse reduction., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective: Women with multiple sclerosis are often diagnosed and treated during their reproductive years. Limited data are available on the safety of treatment during pregnancy. The Betaseron Pregnancy Registry prospectively monitored women exposed to interferon β-1b (IFNβ-1b) during pregnancy to estimate the rates of birth defects, spontaneous abortions (SABs) and other negative outcomes in this population., Design: From 2006 to 2011, this observational registry enrolled women exposed prior to conception or during pregnancy (but prior to or without abnormalities on prenatal screening). Follow-up continued from enrolment through the 4-month paediatric visit., Setting: Patients in the USA who met these criteria were enrolled in the registry., Results: The registry enrolled 99 pregnant women; 3 were lost to follow-up. The earliest exposure to IFNβ-1b occurred during the first trimester for 95 pregnancies and in the third trimester for 1 pregnancy. There were 99 birth outcomes (3 twins), including 86 (86.9%) live births, 11 (11.1%) SABs and 2 (2%) stillbirths. Birth defects were reported in five (5.1%) cases. Rates of birth defects and SAB were not significantly different from population comparators. No developmental concerns were identified at the 4-month paediatric visit., Conclusions: The small sample size limits the ability to draw definitive conclusions; however, there was no pattern to suggest increased negative outcomes with IFNβ-1b., Clinical Trials Registration Number: NCT00317564.

Pregnancy is a major concern in multiple sclerosis (MS), because the typical patient is a young woman of childbearing age. This article reviews the impact of pregnancy on MS. Disease activity decreases, particularly during the last trimester. There is a temporary rebound of disease activity in the 3 months postpartum. Pregnancy and the postpartum period have many implications for counseling and for therapeutic decision making in MS., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Since 1993, six disease-modifying therapies for multiple sclerosis (MS) have been proven to be of benefit in rigorous phase III clinical trials. Other agents are also available and are used to treat MS, but definitive data on their efficacy is lacking. Currently, disease-modifying therapy is used for relapsing forms of MS. This includes clinically isolated syndrome/first-attack high-risk patients, relapsing patients, secondary progressive patients who are still experiencing relapses, and progressive relapsing patients. The choice of agent depends upon drug factors (including affordability, availability, convenience, efficacy, and side effects), disease factors (including clinical and neuroimaging prognostic indicators), and patient factors (including comorbidities, lifestyle, and personal preference). This review will discuss the disease-modifying agents used currently in MS, as well as available alternative agents.

Objective: To determine neurology training opportunities available to medical students and to define factors that influence program choice., Methods: All neurology residency program directors and a random sample of residents were surveyed. Resident questions related to application, interview, and training experience. Directors' questions focused on ways their department generated interest in clinical neurosciences., Results: Medical schools introduce students to clinical neurology primarily through required clerkships. Contact time averages less than 4 weeks and emphasizes inpatient encounters. Preceptorships with neurology faculty do not exist at almost 40% of schools and only 14% have neuroscience tracks. Nearly all residency applicants matched their first or second choice. The majority declined at least one interview and 39% failed to rank at least one site they visited. When choosing where to apply, the programs' reputation and geographic considerations were paramount. When making a rank list, interactions with faculty and residents at interview were most important. Residents generally reported satisfaction with their programs and attribute morale to supportive relationships with faculty and residents., Conclusions: Neurology programs may be able to enhance students' impression of neurology through changes in their clinical experience and development of venues for more meaningful relationships with faculty. Attention to the residents' personal needs may increase the likelihood of matching the best available candidates and ensuring their satisfaction.

Background: Establishing a causal relationship between optic neuritis and Lyme disease (LD) has been hampered by technical limitations in serologic diagnosis of LD. Even so, there is a general impression that optic neuritis is a common manifestation of LD., Methods: Retrospective case analysis of Lyme serology in 440 patients with optic neuritis examined between 1993 and 2003 in a single neuro-ophthalmic practice at Stony Brook University Medical Center, Suffolk County, New York, a region hyper-endemic for LD., Results: Lyme enzyme-linked immunosorbent assay (ELISA) was positive in 28 (6.4%) patients with optic neuritis, three of whom had syphilis with cross-reactive antibodies. Among the remaining 25 ELISA-positive patients, optic neuritis could be confidently attributed to LD in only one case, a patient with papillitis. The other 24 cases had reactive Lyme serologies related to a history of LD years earlier, asymptomatic exposure, false-positive results, or non-specific humoral expansion. The ELISA in these 24 cases were weakly positive and the Western blots were negative by Centers for Disease Control criteria. There were no significant clinical differences between the 25 seropositive optic neuritis cases and 50 seronegative optic neuritis cases., Conclusions: Based on these cases and a review of the literature, there is insufficient evidence for a causal link between LD and retrobulbar optic neuritis or neuroretinitis. There is sufficient evidence to establish a causal link between LD and papillitis and posterior uveitis.

Substantially more women than men develop multiple sclerosis (MS), but information about the effects of MS and gender-specific issues such as pregnancy, breastfeeding, menstruation and hormone use is lacking. A survey study of neurologists' practice patterns was undertaken to elicit information about gender-specific topics and the use of disease-modifying MS therapies (DMT) including the interferons and glatiramer acetate (GA). A total of 147 surveys were returned. Half of respondents require patients to discontinue DMT during pregnancy, while 35% encourage discontinuation. Among those who allow patients to continue therapy, half consider GA to be safer during pregnancy than the interferons. Nearly 86% of respondents do not use DMT in patients who are breastfeeding. Among the 11% who actually prescribe during breastfeeding, most recommend GA. Neurologists generally leave the decision to breastfeed up to patients, and most refer patients to obstetrician/gynaecologists for counselling about contraception or hormone replacement therapy. The survey results described here provide insight into how neurologists manage reproductive health issues among women with MS.

We describe the results of a proof-of-principle to measure the potassium content in the human brain using the natural radioisotope (40)K that is in equilibrium with the stable isotopes of potassium, (39)K and (41)K. A fixed relationship exists between radioactive potassium and the total potassium in the brain, which in turn reflects the brain's cell mass and intracellular water compartment. Accordingly, we explored whether measurements of brain potassium could serve as possible indicators of intracellular cerebral edema. We designed, built, and then calibrated our system using a spherical phantom containing KCl salt dissolved in water at levels comparable to those in the human brain. Emitted radiation was detected using sodium iodide (Nal) and high-purity germanium (HP-Ge) detectors. Our results with phantoms and with five volunteers demonstrate the feasibility of measuring potassium at the levels normally present in human brain tissue. We plan to extend the system to detect the onset of brain edema in patients with multiple sclerosis.

Mitoxantrone is the first drug approved for the treatment of secondary progressive multiple sclerosis (SPMS) in the United States. This assessment considers use of mitoxantrone in the treatment of MS. Mitoxantrone probably reduces the clinical attack rate and reduces attack-related MRI outcomes in patients with relapsing MS (Type B recommendation). Also, mitoxantrone may have a beneficial effect on disease progression in patients with MS whose clinical condition is worsening (Type B recommendation). The potential for serious toxicity of mitoxantrone, however, must be taken into account when considering this therapy in individual patients. Moreover, because the potential clinical benefits on disease progression appear to be only modest, the results of the single phase III trial should be replicated in another (and hopefully much larger) clinical study before this agent is widely recommended for the treatment of patients with MS.

Advancements in imaging technologies and newly evolving treatments offer the promise of more effective management strategies for MS. Until recently, confirmation of the diagnosis of MS has generally required the demonstration of clinical activity that is disseminated in both time and space. Nevertheless, with the advent of MRI techniques, occult disease activity can be demonstrated in 50 to 80% of patients at the time of the first clinical presentation. Prospective studies have shown that the presence of such lesions predicts future conversion to clinically definite (CD) MS. Indeed, in a young to middle-aged adult with a clinically isolated syndrome (CIS), once alternative diagnoses are excluded at baseline, the finding of three or more white matter lesions on a T2-weighted MRI scan (especially if one of these lesions is located in the periventricular region) is a very sensitive predictor (>80%) of the subsequent development of CDMS within the next 7 to 10 years. Moreover, the presence of two or more gadolinium (Gd)-enhancing lesions at baseline and the appearance of either new T2 lesions or new Gd enhancement on follow-up scans are also highly predictive of the subsequent development of CDMS in the near term. By contrast, normal results on MRI at the time of clinical presentation makes the future development of CDMS considerably less likely.

Objective: To determine whether post Lyme syndrome (PLS) is antibiotic responsive., Methods: 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., Results: 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., Conclusions: 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.

The objective of this study was to determine the clinical characteristics of multiple sclerosis (MS) in African American (AA) patients in the New York State Multiple Sclerosis Consortium (NYSMSC) patient registry. The NYSMSC is a group of 18 MS centers throughout New York State organized to prospectively assess clinical characteristics of MS patients. AAs comprise 6% (329) of the total NYSMSC registrants (5602). Demographics, disease course, therapy, and socioeconomic status were compared in AA registrants versus nonAfrican Americans (NAA). There was an increased female preponderance and a significantly younger age at diagnosis in the AA group. AA patients were more likely to have greater disability with increased disease duration. No differences were seen in types of MS and use of disease modifying therapies. Our findings suggest a racial influence in MS. Further genetic studies that consider race differences are warranted to elucidate mechanisms of disease susceptibility.

We developed a simple method to detect apolipoprotein E (Apo E) polymorphism distribution in approximately 20 microL of unconcentrated cerebrospinal fluid (CSF). A combination of isoelectric focusing in 3 M urea gel and immunoblotting was employed. Apo E phenotypes were identified in CSF samples from 45 patients with probable Alzheimer disease (AD), 15 with multiple sclerosis (MS), and 25 with other neurological diseases (OND). When the data were compared with a set of matched plasma samples, the results were identical. The method is useful for Apo E phenotyping from fresh or frozen unconcentrated CSF, when blood or plasma is not available., (Copyright 2003 Wiley-Liss, Inc.)

Background: Interferon beta (IFNbeta) reduces relapses and MRI activity in relapsing-remitting MS (RRMS), with variable effects on disability. The most effective dose regimen remains controversial., Methods: This randomized, controlled, multicenter trial compared the efficacy and safety of IFNbeta-1a (Rebif) 44 micro g subcutaneously three times weekly (tiw), and IFNbeta-1a (Avonex) 30 micro g IM once weekly (qw) in 677 patients with RRMS. Assessors blinded to treatment performed neurologic and MRI evaluations. The primary endpoint was the proportion of patients who were relapse free at 24 weeks; the principal MRI endpoint was the number of active lesions per patient per scan at 24 weeks., Results: After 24 weeks, 74.9% (254/339) of patients receiving IFNbeta-1a 44 micro g tiw remained relapse free compared with 63.3% (214/338) of those given 30 micro g qw. The odds ratio for remaining relapse free was 1.9 (95% CI, 1.3 to 2.6; p = 0.0005) at 24 weeks and 1.5 (95% CI, 1.1 to 2.1; p = 0.009) at 48 weeks, favoring 44 micro g tiw. Patients receiving 44 micro g tiw had fewer active MRI lesions (p < 0.001 at 24 and 48 weeks) compared with those receiving 30 micro g qw. Injection-site reactions were more frequent with 44 micro g tiw (83% vs 28%, p < 0.001), as were asymptomatic abnormalities of liver enzymes (18% vs 9%, p = 0.002) and altered leukocyte counts (11% vs 5%, p = 0.003) compared with the 30 micro g qw dosage. Neutralizing antibodies developed in 25% of 44 micro g tiw patients and in 2% of patients receiving 30 micro g qw., Conclusions: IFNbeta-1a 44 micro g subcutaneously tiw was more effective than IFNbeta-1a 30 micro g IM qw on all primary and secondary outcomes investigated after 24 and 48 weeks of treatment.

We used quantitative magnetic resonance (MR) spectroscopic imaging with T1-based image segmentation to evaluate the subtypes of multiple sclerosis (MS) (eight patients each group of relapsing-remitting [RR], secondary progressive [SP] and primary progressive [PP]). There was no significant difference in age between the PP group with the RP, SP or control group. We found that the metabolite ratio of choline/NA from the periventricular white matter region was not significantly different between the RR and SP groups. Using an ANOVA, the ratios of periventricular choline/NA or creatine/NA of these combined groups were significantly higher than the PP and control groups. Quantification of these data suggest that the major cause of the elevation of these parameters is due to an increase in choline and creatine in the RR group while NA is decreased in the SP group. Thus, early PP disease appears to be relatively intact with respect to neuronal loss.

Lyme disease has emerged as a major infection with frequent neurologic manifestations. These manifestations probably reflect several predominantly indirect pathogenetic mechanisms and involve host, vector, and organism factors. With early diagnosis and appropriate antibiotic treatment, patients do well. Because culture is not reliable, diagnosis has relied on positive serology to document exposure. Serology should improve as second-generation assays become available. Although there is a preventive vaccine based on the lipoprotein OspA, newer vaccines in development may prove more desirable. Lyme disease provides a valuable model to study how infectious pathogens cause neurologic disease.

The current approach to the use of interferon (IFN) beta in the treatment of multiple sclerosis (MS) is, in general, conservative. However, recent findings about early events in MS and data on dose-response relationships with IFN beta indicate that such an approach may be suboptimal. Four lines of evidence suggest that delays in the initiation of therapy with IFN beta may be detrimental: 1) axonal damage secondary to inflammation starts very early in the course of MS; 2) pathological events occurring early in MS are predictive of the future course of the disease; 3) inflammatory activity in relapsing MS is not confined to episodes of clinical impairment, but often starts before the first such episode and generally continues during remissions; and 4) the immune-mediated activity that underlies MS may become more difficult to control as the disease progresses. An early treatment strategy is also supported by data from two recently published clinical studies. In addition, preclinical and clinical results suggest that the beneficial effects of IFN may be dose- and frequency-dependent. Taken together, these findings indicate that treatment with IFN beta should be started as early as possible in the course of MS, and suggest that, in order to maximize patent benefit, the highest possible dose of IFN beta should be chosen.

This article describes a family characterized by combined cardiomyopathy and nonspecific skeletal myopathy who present in the third to fifth decades with cardiac manifestations but earlier have evidence of subtle skeletal muscle dysfunction. They differ from previously defined syndromes and potentially represent a different genetic expression or mutation. Cardiomyopathy presents with atrial arrhythmias including AF and atrial flutter. Life-threatening ventricular tachyarrhythmias occur next with onset of ventricular dysfunction. Electrophysiological study revealed sustained monomorphic VT. Affected family members benefitted from an ICD and progression to congestive heart failure (CHF) occurred late. Skeletal myopathy continues with marked progressive muscle weakness and inability to ambulate without assistance. Genetic analysis is currently ongoing. Neurological evaluation in all three family members revealed nonspecific myopathy affecting the psoas and iliopsoas muscles. Atrophy and wasting of the facial and temporalis muscles were common. Skeletal muscle biopsy revealed myofiber atrophy consistent with myopathy.

Recent studies have demonstrated the utility of magnetic resonance (MR) spectroscopic imaging to evaluate axonal integrity in patients with multiple sclerosis (MS). Patient status in MS is frequently assessed by the Expanded Disability Status Scale, which emphasizes ambulation but underestimates the contribution of cognitive factors. Yet, cognitive functions of memory and processing are known to be impaired in MS. We used quantitative MR spectroscopy to determine this relation between cognitive function and N-acetyl aspartate (NAA) levels. We find a significant correlation (r = .63, p < .005) for the left periventricular (PV) NAA concentrations with performance on the verbal Selective Reminding Test. Right PVNAA was significantly (p < .02) correlated with the Tower of Hanoi performance, with r = .58.

The allergist may frequently be involved with cases of Lyme disease. There are at least three reasons for this. First, the major symptom is often a rash that brings into the differential diagnosis several diseases that the allergist is likely to have expertise in; therefore, the allergist's role as a diagnostician is very important. The second reason is that the Borrelia burgdorferi (Bb) infection is treated with antibiotics and the patients may frequently develop reactions that may be immune-mediated. The allergist's expertise in diagnosis and management of allergic reactions is important. The third reason is that there is no established laboratory diagnostic test so that the clinician must use the existing tests, most often serologic, with their limitations, in the context of a history and physical. The allergist as an immunologist can be very helpful in the proper interpretation of the test results. The differential of the rash and the immune response to the infecting agent is described.

The authors used data collected prospectively during a multicenter trial in 133 patients with secondary progressive MS to assess the relative sensitivity of quantitative functional tests and traditional measures, including the Expanded Disability Status Scale (EDSS) and Ambulation Index. Quantitative functional measures worsened in 69% of patients during an average of 6 months of observation, whereas the Clinical Global Impression of Change worsened in 33% and the EDSS worsened in 25% of patients. These changes should be interpreted in the context of the test-retest reliability for each measure.

Objective: To assess the safety, tolerability, and biologic and clinical activity of a solubilized complex comprised of human leukocyte antigen-DR2 with myelin basic protein84-102 (AG284)in patients with secondary progressive MS., Background: Soluble species-specific major histocompatibility complex myelin basic protein91-103 complexes ameliorate disease in a dose-dependent manner when administered to SJL/J mice with chronic relapsing experimental allergic encephalomyelitis. Preincubation with AG284 reduces the proliferative response of a DR2-restricted, myelin basic protein84-102-reactive T cell clone, derived from a MS patient, to myelin basic protein84-102 in the presence of autologous antigen-presenting cells., Methods: Thirty-three patients with secondary progressive MS were randomly assigned to receive three alternate day IV doses of AG284 or placebo in a double-masked dose escalation study. The primary outcome was safety and tolerability. Secondary outcomes included a comparison of pre- and post-treatment gadolinium-enhanced brain MRI activity, Kurtzke Expanded Disability Status Scale, and Nine Hole Peg Test scores., Results: The frequency of adverse events was similar in the AG284 and placebo recipients. No significant treatment effect was detected by Expanded Disability Status Scale, Nine Hole Peg Test, or number of new gadolinium-enhancing MRI lesions., Conclusions: AG284 as administered during this study was safe and well tolerated. Further studies are warranted to determine the biologic activity and clinical efficacy of this potential treatment for MS.

Acute disseminated encephalomyelitis is a monophasic, immune-mediated disorder that produces multifocal demyelinating lesions within the central nervous system. It is characterized clinically by the acute onset of neurologic abnormalities, including varying degrees of mental state changes ranging from drowsiness to coma. It is unusual for the illness to present as an isolated acute psychosis. The case of a 14-year-old female with biopsy-confirmed acute disseminated encephalomyelitis, who was initially diagnosed with an acute psychiatric disorder, is presented, and published reports on this unusual manifestation are reviewed. A Medline database search was performed from 1965 to 1999, using the terms acute disseminated encephalomyelitis, postvaccinal encephalomyelitis, postinfectious encephalomyelitis, and measles encephalomyelitis, combined with the terms psychosis, psychiatric disorder, and behavioral disorder. Selected cross-referenced reports were also reviewed. Nine patients were identified who presented with acute psychosis. We conclude that, although rare, acute disseminated encephalomyelitis can present as an acute psychosis. This immune-mediated condition should be included in the differential diagnosis of neurologic disorders presenting as a psychiatric illness.

Context: Diagnosis of infection with Borrelia burgdorferi, the cause of Lyme disease (LD), has been impeded by the lack of effective assays to detect active infection., Objective: To determine whether B. burgdorferi-specific immune complexes are detectable during active infection in LD., Design, Setting, and Patients: Cross-sectional analysis of serum samples from 168 patients fulfilling Centers for Disease Control and Prevention surveillance criteria for LD and 145 healthy and other disease controls conducted over 8 years. Tests were performed blinded., Main Outcome Measure: Detection of B. burgdorferi immune complexes by enzyme-linked immunosorbent assay and Western blot., Results: The B. burgdorferi immune complexes were found in 25 of 26 patients with early seronegative erythema migrans (EM) LD; 105 of 107 patients with seropositive EM LD; 6 of 10 samples that were seronegative [corrected] with culture-positive EM; 0 of 12 patients who were treated and recovered from LD; and 13 of 13 patients with neurologic LD without EM. Among 147 controls, B. burgdorferi immune complex was found in 0 of 50 healthy individuals; 0 of 40 patients with persistent fatigue; 0 of 7 individuals with frequent tick exposure; and 2 of 50 patients with other diseases., Conclusion: These data suggest that B. burgdorferi immune complex formation is a common process in active LD. Analysis of the B. burgdorferi immune complexes by a simple technique has the potential to support or exclude a diagnosis of early as well as active LD infection.

Meningitis can be subdivided based on time course of onset and duration, cerebrospinal fluid (CSF) profile, and underlying origins into acute aseptic and septic meningitis, recurrent meningitis, and chronic meningitis. These are distinct syndromes that require different management strategies. Most cases of meningitis are caused by infection. The causal agent is generally predictable based on the type of meningitis, host factors, and clues from the history and examination. CSF examination remains the critical diagnostic test.

We have obtained a current profile of multiple sclerosis York State through a centralized patient registry and standardized data collection instrument associated with the New York State Multiple Sclerosis Consortium of 12 MS centers located throughout the state. Data from the first 3019 patients with clinically definite MS revealed a clear relationship between MS disease type, duration of disease, and severity of physical disability. Patients with relapsing disease had disease durations approximately half as long as those with progressive forms of the disease (means approximately 6 years versus 11 years). The majority of patients with relapsing disease had Expanded Disability Status Scale (EDSS) scores of 4.0 or less (self-sustained, fully ambulatory), whereas the majority of patients with progressive disease types had EDSS scores of 6.0 or greater (at least unilateral assist for walking). These findings emphasize the importance of early intervention in patients with relapsing disease to slow or prevent the accumulation of physical disability associated with progressive types of disease. Progressive disease was associated with lack of full-time employment and being disabled before the age of 60 years. Patients with relapsing disease were more likely to be employed and have private forms of insurance, whereas patients with progressive types of disease were more likely to have government-supported insurance to cover medical expenses.

Objective: To evaluate evidence-based data on adjunctive glucocorticoid therapy in central nervous system bacterial infections., Design: A literature review of studies, particularly controlled trials, that have evaluated dexamethasone therapy for acute bacterial meningitis and glucocorticoid therapy for tuberculous meningitis., Main Outcome Measures: Clinical outcomes were mortality and morbidity rates. Morbidity involved sensorineural hearing loss and other neurologic deficits (motor or behavioral disturbances, epilepsy, cranial nerve palsy, hydrocephalus, and psychomotor retardation)., Results: The evidence-based data support adjunctive dexamethasone therapy for children with Haemophilus influenzae meningitis. However, the optimal duration of therapy is not defined. Data are supportive but not conclusive that dexamethasone benefits meningitis caused by other bacterial agents and meningitis in adults. The evidence-based data are supportive but not conclusive that adjunctive glucocorticoid therapy benefits patients with tuberculous meningitis, particularly those with more severe infection., Conclusions: Although adjunctive glucocorticoid therapy may be beneficial in both acute bacterial meningitis and more severe tuberculous meningitis, there are conclusive data only for H influenzae meningitis in children. For acute bacterial meningitis, further studies are needed to clarify the optimal duration of dexamethasone therapy (2 vs 4 days), whether this therapy should be used routinely for adults with meningitis, and whether it should be used for pathogens other than H influenzae. For tuberculous meningitis, further studies are needed to provide conclusive evidence of benefit.

We measured free kappa (kappa) and lambda (lambda) light chains in urine from patients with definite multiple sclerosis (MS), other neurologic diseases (OND), and normal controls by using an enzyme linked immunosorbent assay. Both kappa and lambda light chains were higher in MS than OND or controls. In seven of eight relapsing-remitting (R-R) MS patients serial studies showed that urinary kappa chains were elevated during periods of worsening, and decreased during clinical recovery. In contrast, the levels of kappa chains did not correlate with clinical activity in 10 progressive (P) MS patients. Further correlation of urinary light chains with neurologic evaluations in R-R and P MS patients over a longer period are needed to determine their clinical and biological relevance.

Objective: To determine the relative frequency of abnormal cerebrospinal fluid (CSF) findings in children with Lyme disease-associated facial nerve palsy., Design: A clinical series. A prospective evaluation was undertaken of the condition of children seen between 1988 and 1996 at a single medical center in a Lyme disease endemic area., Patients: Forty children (24 boys and 16 girls, aged 3-19 years) with new onset facial nerve palsy who met the Centers for Disease Control and Prevention case definition of Lyme disease., Interventions: Neurologic examinations. Cerebrospinal fluid analysis., Main Outcome Measures: Rates of abnormal CSF findings: white blood cell count, protein level, and Borrelia burgdorferi-specific CSF assays., Results: Cerebrospinal fluid white blood cell count, protein level, or both were abnormal in 27 (68%) of the children. Thirty-six (90%) of the 40 children had a CSF abnormality consistent with central nervous system infection or immune involvement by B burgdorferi. Of the 22 children with CSF pleocytosis, only 7 (32%) had headache and none had meningeal signs., Conclusions: Most children with Lyme disease-associated facial nerve palsy have CSF abnormalities. Our studies indicate that, in endemic areas, facial nerve palsy in children may be a marker of Lyme disease and occult meningitis. When Lyme disease is suspected, CSF should be examined; in some cases, it may be helpful to expand beyond routine CSF studies to look at a battery of B burgdorferi-specific assays.

Background: Patients with chronic fatigue syndrome (CFS) and post-Lyme syndrome (PLS) share many features, including symptoms of severe fatigue and cognitive difficulty., Objective: To examine the neuropsychiatric differences in these disorders to enhance understanding of how mood, fatigue, and cognitive performance interrelate in chronic illness., Methods: Twenty-five patients with CFS, 38 patients with PLS, and 56 healthy controls participated in the study. Patients with CFS met 1994 criteria for CFS and lacked histories suggestive of Lyme disease. Patients with PLS were seropositive for Lyme disease, had met the Centers for Disease Control and Prevention criteria, or had histories strongly suggestive of Lyme disease and were experiencing severe fatigue that continued 6 months or more following completion of antibiotic treatment for Lyme disease. All subjects completed self-report measures of somatic symptoms and mood disturbance and underwent neuropsychological testing. All patients also underwent a structured psychiatric interview., Results: Patients with CFS and PLS were similar in several somatic symptoms and in psychiatric profile. Patients with CFS reported more flulike symptoms than patients with PLS. Patients with PLS but not patients with CFS performed significantly worse than controls on tests of attention, verbal memory, verbal fluency, and motor speed. Patients with PLS without a premorbid history of psychiatric illness did relatively worse on cognitive tests than patients with PLS with premorbid psychiatric illness compared with healthy controls., Conclusions: Despite symptom overlap, patients with PLS show greater cognitive deficits than patients with CFS compared with healthy controls. This is particularly apparent among patients with PLS who lack premorbid psychiatric illness.

Infections are a recognized cause of secondary vasculitis. A variety of pathogens have a propensity to involve blood vessels. Vasculitis, non-vasculitic vasculopathy, and mycotic aneurysms lead to infarction and hemorrhage of nervous system tissue. Treatment of infection-related vasculitis should include appropriate antimicrobial therapy directed against the offending pathogen, and appropriate management of cerebrovascular complications.

Lyme disease is the major tick-borne disease, caused by Borrelia burgdorferi (Bb). Neurological involvement is common in all stages. In vivo expression of Bb antigens (Ags) and the immune response to them has not been well investigated in the cerebrospinal fluid (CSF). Upregulation of outer surface protein (Osp) C and concomitant downregulation of OspA before tick inoculation of the spirochete has been reported in skin and blood in animals. CSF OspA Ag in early disease suggests otherwise in CSF. Early Ag expression and IgM response in human CSF was investigated here. Paired CSF and serum was collected from 16 early, predominantly erythema migrans Lyme disease patients with neurologic problems, 13 late Lyme disease patients, and 19 other neurologic disease (OND) controls. Samples were examined for IgM reactivity to recombinant Bb-specific Osps using ELISA and immunoblot. Of 12 early Lyme disease patients with neurologic involvement with both CSF and serum IgM against OspC, 7 (58%) had IgM to OspA (n = 5) or OspB (n = 2) that was restricted to the CSF, not serum. Overall, 12 of 16 (75%) of these early Lyme disease patients with neurologic involvement had CSF and serum IgM against OspC. Only 3 of 13 (23%) late Lyme disease patients and none of 19 OND controls had CSF IgM directed against OspC. In conclusion, in CSF, OspC and OspA can be coexpressed, and IgM response to them occurs in early Lyme disease patients with neurologic involvement. This biologic finding may also provide a discriminating marker for CNS infection in Lyme disease.

Objective: We measured measles-specific IgA in matched pairs of cerebrospinal fluid (CSF) and sera of patients with subacute sclerosing panencephalitis (SSPE), multiple sclerosis (MS), other central nervous system (CNS) infectious diseases (INF) and other neurological diseases (OND) by using enzyme linked immunosorbent assay., Materials and Methods: CSF and sera from 23 patients with SSPE, 15 with MS, 14 with INF, and 15 with OND were included in the study., Results: The ratios of measles-specific IgA in CSF to serum were increased in SSPE patients compared to patients with MS, INF or OND., Conclusion: The data indicate a local production of measles-specific IgA in the CNS of SSPE patients.

Objective: Lyme disease must be included in the differential diagnosis of acute facial paralysis in endemic areas. When facial nerve palsy occurs as an isolated finding, the diagnosis of Lyme disease may not be readily apparent. The goal of the present study was to evaluate the frequency with which Lyme disease could be diagnosed based on clinical symptoms alone., Study Design and Setting: This was a retrospective chart review conducted at a tertiary hospital on Long Island, New York, an area endemic for Lyme disease., Patients: The study population was composed of 50 patients with facial nerve palsy who were seropositive for Lyme disease (or had Lyme disease otherwise clinically proven)., Main Outcome Measures: Clinical data were initially used to classify patients as having definite, probable, or possible Lyme disease, using the surveillance criteria of the Centers for Disease Control and Prevention., Results: In the majority of cases, the diagnosis of Lyme disease could not be made from clinical data alone. Specific findings, such as erythema migrans and meningoencephalitis, occurred only inconsistently, and serologic or cerebrospinal fluid tests were usually necessary to establish the diagnosis. Intrathecal antibody production was found in a high proportion of patients., Conclusions: In endemic areas, Lyme disease should be suspected as a cause of acute facial nerve palsy even in the absence of other clinical symptoms. Cerebrospinal fluid serology is helpful in confirming the diagnosis and planning therapy. Central nervous system infection may be common in Lyme disease facial nerve palsy.

Proinflammatory cytokines (interleukin [IL]-1beta, tumor necrosis factor [TNF]-alpha, and IL-6) and soluble intercellular adhesion molecule-1 (sICAM-1) were measured in paired cerebrospinal fluid (CSF) and serum samples from patients with subacute sclerosing panencephalitis (SSPE), multiple sclerosis (MS), or other neurologic diseases (OND) by ELISA. IL-1beta was significantly increased in CSF of the SSPE group compared with levels in the MS or OND group. IL-1beta CSF/serum ratios were higher in the SSPE than in the MS or OND group. TNF-alpha and IL-6 levels were similar in the 3 groups. CSF sICAM-1 was higher in the SSPE group than in the MS or OND group. sICAM-1 CSF/serum ratios were higher in the SSPE than the OND group. The increased CSF/serum ratios of IL-1beta and sICAM-1 in SSPE indicate synthesis of IL-1beta and sICAM-1 in the central nervous system and may be important in the pathogenesis of disease.

We determined the effect of influenza vaccine in patients with relapsing/remitting MS. Considerable controversy surrounds the question of whether to administer influenza vaccines to MS patients. Prevention of a febrile viral illness is clearly desirable in MS, and previous studies suggest that immunization is safe. Despite this, many clinicians avoid vaccination because they fear precipitating an MS exacerbation. We conducted a multicenter, prospective, randomized, double-blind trial of influenza immunization in patients with relapsing/remitting MS. In the autumn of 1993, 104 patients at five MS centers received either standard influenza vaccine or placebo. Patients were followed for 6 months for evaluation of neurologic status and the occurrence of influenza. Influenza was operationally defined as fever > or = 38 degrees C in the presence of coryza, cough, or sore throat at a time when the disease was present in the community. Attacks were defined in the standard manner, requiring objective change in the examination. Patients were examined at 4 weeks and 6 months after inoculation and were contacted by telephone at 1 week and 3 months. They were also examined at times of possible attacks but not when they were sick with flu-like illness. Three vaccine patients and two placebo patients experienced attacks within 28 days of vaccine (no significant difference). Exacerbation rates in the first month for both groups were equal to or less than expected from published series. The two groups showed no difference in attack rate or disease progression over 6 months. Influenza immunization in MS patients is neither associated with an increased exacerbation rate in the postvaccination period nor a change in disease course over the subsequent 6 months.

Borrelia burgdorferi is a tick-borne spirochete and the etiologic agent of Lyme disease. This pathogen now accounts for 91% of vector-borne infections in the United States, and from a public health viewpoint is one of our major emerging infectious disorders. Specific properties of B. burgdorferi have resulted in diagnostic problems, including the lack of a readily available laboratory assay to detect active infection. Most laboratory testing for Lyme disease relies on serologic documentation of prior exposure to the agent. However, such testing detects asymptomatic infections, and does not detect seronegative infections. In addition, antibody tests for Lyme disease are not standardized. Cases of Lyme disease are both underdiagnosed and overdiagnosed. This review will discuss the spirochetal properties which contribute to diagnostic difficulties, will discuss current laboratory diagnostic tests, including serology and detection of B. burgdorferi DNA, and will discuss diagnostic tests in development, including recombinant-based serologic assays and detection of B. burgdorferi antigens.

Background: Amantadine hydrochloride and pemoline, both frequently used to treat the fatigue of multiple sclerosis (MS), may also improve attention and other cognitive functions in MS. To our knowledge, these agents have never been compared in a placebo-controlled trial of patients with MS., Objective: To evaluate the effects of amantadine and pemoline on cognitive functioning in MS., Methods: A total of 45 ambulatory patients with MS and severe fatigue were treated for 6 weeks with amantadine, pemoline, or placebo using a parallel group design. They underwent comprehensive neuropsychological testing to determine treatment effects on cognitive functioning. Primary outcome measures were tests of attention (Digit Span, Trail Making Test, and Symbol Digit Modalities Test), verbal memory (Selective Reminding Test), nonverbal memory (Benton Visual Retention Test), and motor speed (Finger Tapping Test)., Results: Fatigue did not significantly correlate with any of the neuropsychological outcome measures at baseline or after treatment. All three treatment groups improved on tests of attention (P < .003), verbal memory (P < .001), and motor speed (P < .002). There were no significant differences between amantadine, pemoline, and placebo., Conclusions: Cognitive functioning in MS is independent of fatigue. Neither amantadine nor pemoline enhances cognitive performance in MS compared with placebo.

The present study addresses issues regarding the location of neural sources (i.e. generators) of human auditory evoked potentials (AEPs), and the pattern of neural conduction in the auditory pathway. AEPs were recorded from fifteen patients with multiple sclerosis (MS) and compared to normals. The recordings included auditory brainstem responses (ABRs), mid-latency responses (MLRs), and long-latency responses (LLRs). AEP latency abnormalities were related to the locus of demyelinating lesions, as determined by magnetic resonance imaging (MRI) scans. The data demonstrated several anatomical patterns relating abnormal ABR wave intervals and abnormal MRI signals. From these patterns specific loci for ABR neural sources in the brainstem might be postulated. In addition, the earlier the ABR waves, the more unilateral the abnormalities appeared, suggesting bilateral sources for later waves. The MLRs were highly correlated with ABR wave V and were associated with greater abnormality in MRI signals in midbrain and forebrain regions. In general, patients with abnormal LLRs also had widespread AEP and MRI abnormalities, supporting a multiple source approach for the N1 wave of the LLRs. The observation that LLRs were only abnormal in the presence of bilateral ABR abnormalities suggests a cross wiring which would serve as a compensatory mechanism for unilateral disturbances. The AEP data showed dissociation between early and late wave abnormalities, thus supporting parallel channels for neural conduction in the central auditory system. Such a model calls for some degree of independence of AEP generators along the auditory pathway.

The aim of this clinical review is to highlight recent advances in immunology, as well as new information from selected other areas, which have led to a better appreciation of the neuroimmunologic mechanisms involved in Multiple sclerosis (MS). New data on immunopathology, the cytokine network, and the role of oligodendrocytes, lymphocytes, and endothelial cells in this disease, have produced novel therapeutic approaches. New information on clinical course and neuroimaging disease features, as well as the role of genetic factors and infectious agents, have also improved our understanding of the immune basis for MS.

Objective: To determine the relative efficacy of amantadine, pemoline, and placebo in treatment of multiple sclerosis (MS)-related fatigue., Background: Fatigue is a complication of MS. Both pemoline and amantadine have been used to treat MS fatigue, but their relative efficacy is not known., Methods: Amantadine, pemoline, and placebo were compared in a randomized, double-blind, placebo-controlled study using a parallel-group design. Ninety-three ambulatory MS patients completed the study. Primary outcome measures were the fatigue severity scale (FSS); the MS-specific fatigue scale (MS-FS); and subjective response determined by verbal self-report. Secondary outcome measures consisted of assessments of sleep, depression, and vitality. Repeated-measures analysis of variance with planned post-hoc contrasts and Fisher's exact test were used to compare treatment response., Results: Amantadine-treated patients showed a significantly greater reduction in fatigue, as measured by the MS-FS, than did patients treated with placebo (p = 0.04). By verbal report at the end of the study, 79% of patients treated with amantadine versus 52% treated with placebo and 32% treated with pemoline preferred drug therapy compared with no treatment (p = 0.03). No significant differences in any primary outcome measures were noted between pemoline and placebo. Neither amantadine nor pemoline affected sleep or depression relative to placebo., Conclusion: Amantadine was significantly better than placebo in treating fatigue in MS patients, whereas pemoline was not. The benefit of amantadine was not due to changes in sleep, depression, or neurologic disability.