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Biomedical subjects

L B Krupp

Publications and source records attributed to L B Krupp.

At least 19 recordsLinked to original sources
PubMed2003

Study and treatment of post Lyme disease (STOP-LD): a randomized double masked clinical trial.

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.

Adult↗
PubMed2003

Cognitive performance and MR markers of cerebral injury in cognitively impaired MS patients.

OBJECTIVE: To relate neuropsychological performance to measures of cerebral injury in persons with MS selected for cognitive impairment. METHODS: Participants were 37 individuals with relapsing-remitting (59.5%) and secondary progressive (40.5%) MS. They were tested at baseline as part of a clinical trial to enhance cognition with an acetylcholinesterase inhibitor. Eligibility criteria included at least mild cognitive impairment on a verbal learning and memory task. A modified Brief Repeatable Battery of Neuropsychological Tests formed the core of the behavioral protocol. Neuroimaging measures were central (ventricular) cerebral atrophy, lesion volume, and ratios of N-acetyl aspartate (NAA) to both creatine and choline. RESULTS: A clear, consistent relation was found between cognitive and MR measures. Among neuroimaging measures, central atrophy displayed the highest correlations with cognition, accounting for approximately half the variance in overall cognitive performance. NAA ratios in right hemisphere sites displayed larger correlations than those on the left. Multiple regression models combining the MR measures accounted for well over half the variance in overall cognitive performance. The Symbol Digit Modalities Test was the neuropsychological task most strongly associated with the neuroimaging variables. CONCLUSIONS: If a strong and stable association can be firmly established between cognitive and MR variables in appropriate subsets of MS patients, it might aid in the investigation of interventions to enhance cognition and modify the course of the disease.

Adult↗
PubMed2002

Metabolic differences between multiple sclerosis subtypes measured by quantitative MR spectroscopy.

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.

Aspartic Acid↗
PubMed2001

Fatigue in multiple sclerosis.

Fatigue is among the most common, yet least understood, symptoms of multiple sclerosis (MS) [1.]. It can profoundly disrupt the occupational and social functioning of patients, and is recognized as a criterion for MS disability by the Social Security Administration. Most approaches to fatigue assessment can be classified as either self-report scales or performance-based measures of motor or cognitive output. During the clinical management of fatigue, it is important to consider the role of other MS symptoms on fatigue, as well as that of non-MS-related medical conditions. Management of fatigue in MS often entails both pharmacologic and behavioral components. This article reviews recent developments in the assessment, treatment, and pathogenesis of MS fatigue.

Amantadine↗
PubMed2001

Cognitive dysfunction lateralizes with NAA in multiple sclerosis.

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.

Adult↗
PubMed2000

Are quantitative functional measures more sensitive to worsening MS than traditional measures?

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.

Humans↗
PubMed2000

Fatigue and declines in cognitive functioning in multiple sclerosis.

OBJECTIVE: To determine whether cognitive fatigue, defined as a decline in cognitive performance over a single testing session, could be identified in MS. METHODS: Forty-five individuals with MS and 14 healthy control participants completed a 4-hour session of cognitive testing that involved a baseline neuropsychological battery, a continuous effortful cognitive task (completing mental arithmetic problems administered on a computer), and a repeat neuropsychological battery. Self-report measures of fatigue and affect were completed before each step of the testing session. RESULTS: The pattern of change in cognitive performances over the testing session significantly differed between the MS and control participants. Individuals with MS showed declines on measures of verbal memory and conceptual planning, whereas the control participants showed improvement. Although there were no significant differences between the groups on any of the baseline cognitive measures, the MS participants performed worse than the control subjects on tests of visual memory, verbal memory, and verbal fluency that were repeated following the continuous effortful cognitive task. Both MS and control participants reported increased mental and physical fatigue across the testing session compared with their baseline values. CONCLUSION: Individuals with MS show declines in cognitive performance during a single testing session and fail to show the improvement exemplified by healthy control subjects.

Adult↗
PubMed1999

Psychological states and neuropsychological performances in chronic Lyme disease.

The neuropsychiatric sequelae of chronic Lyme disease remains unclear. This study sought to characterize the psychological status of a group of participants who met criteria for post-Lyme syndrome (PLS). These measures were then used to examine the influence of psychological status on neuropsychological performances. Thirty PLS participants completed a structured psychiatric interview, the Positive and Negative Affect Schedule, the Lyme Symptom Checklist, and a battery of neuropsychological tests. As a group, the PLS participants did not appear to have an elevated incidence of psychiatric disorders, and psychiatric history was not useful for understanding neuropsychological performances or symptom reports. The mood of the PLS participants was characterized by lowered levels of positive affect (PA) and typical levels of negative affect. This combination can be distinguished from depression and is consistent with previous findings of affect patterns in individuals with chronic fatigue syndrome. PA was also linked to both total symptom severity and severity of cognitive complaints, but not to duration of illness, neurological manifestations at initial diagnosis, or treatment history. Relative to published normative data, neuropsychological performances were not in the impaired range on any measure. Neither psychological status nor symptom report were useful for understanding any aspect of cognitive functioning. It is concluded that decreased PA is the most useful marker of psychological functioning in PLS.

Adult↗
PubMed1999

Does process-specific slowing account for cognitive deficits in Lyme disease?

Although several studies have suggested that cognitive slowing is a symptom in Lyme disease, it is not clear whether this slowing is general or relates to specific cognitive tasks. This study examined cognitive speed in 25 Lyme disease patients using a mental arithmetic task. These patients showed significant impairments when initiating the cognitive processes involved in counting, but performed as well as healthy participants (n = 23) when the number of counting increments increased. Lyme patients also performed a speeded perceptual-motor matching task as well as healthy participants. Lyme-related initiation speed deficits were significantly correlated with performance on standardized neuropsychological tests, including the Trail Making Test and the Digit Symbol Test, but not with self-reported depression. These results suggest that the cognitive deficits seen on speeded tasks are process specific in the Lyme patient group, and are not the result of generalized slowing.

Adult↗
PubMed1999

Cognitive processing speed in Lyme disease.

OBJECTIVE: The goal of this study was to more precisely define the nature of the cognitive processing deficits in the patients with Lyme disease. BACKGROUND: Lyme disease has been associated with cognitive disturbances. METHOD: Sixteen patients who met the Centers for Disease Control's case definition for Lyme disease and 15 age- and education-matched control subjects completed two computerized assessments. The first was a matching procedure that assessed perceptual/motor speed. The second task was an alphabet-arithmetic (AA) test that measured the speed of mental arithmetic. On the matching task, subjects judged as true or false simple identity equations (e.g., B + 0 = B). On the AA task, subjects indicated the veracity of equations of the same form as those of the matching task but which required mental arithmetic (e.g., A + 3 = D). The use of this paradigm permits sensory or motor slowing to be distinguished from slowed cognitive processing speed. Also, the tests do not involve automated or overlearned responses. RESULTS: Lyme disease patients and healthy controls did not differ in perceptual/motor speed. However, Lyme disease patients' response times were significantly longer than those of healthy controls during the AA task, demonstrating specific impairments in mental activation speed. CONCLUSIONS: These results suggest that Lyme disease patients show specific deficits when initiating a cognitive process. These impairments are independent of sensory, perceptual, or motor deficits.

Adult↗
PubMed1998

Pain, fatigue, and sleep in eosinophilia-myalgia syndrome: relationship to neuropsychological performance.

Cognitive problems are frequently reported in patients with eosinophilia-myalgia syndrome (EMS). This is the first study to explore, in EMS, the relationship between specific neuropsychological deficits and fatigue and pain. Relationships among depression, sleep disturbance, and neuropsychological deficits in EMS were also examined. Neither fatigue nor pain was correlated with memory impairment. Sleep disturbance was significantly correlated with verbal memory impairment, but not with deficits in visuospatial memory. These results suggest that cognitive loss in EMS cannot be attributed to pain or fatigue. Although some aspects of memory impairment may be associated with disturbed sleep, visual memory deficits are clearly independent of sleep deficits and may result from direct effects of the disease on the central nervous system.

Adult↗
PubMed1997

Simultaneous expression of Borrelia OspA and OspC and IgM response in cerebrospinal fluid in early neurologic Lyme disease.

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.

Adolescent↗
PubMed1997

Post-Lyme syndrome and chronic fatigue syndrome. Neuropsychiatric similarities and differences.

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.

Adult↗
PubMed1997

A multicenter, randomized, double-blind, placebo-controlled trial of influenza immunization in multiple sclerosis.

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.

Double-Blind Method↗
PubMed1996

The effects of amantadine and pemoline on cognitive functioning in multiple sclerosis.

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.

Adolescent↗