Are atraumatic spinal needles as efficient as traumatic needles for lumbar puncture?

The most frequent complication of lumbar puncture is post lumbar puncture headache (PLPH). Recent studies confirmed that the use of atraumatic spinal needles significantly reduces the risk of PLPH. However, the majority of neurologists still use traumatic needles, possibly caused by misconceptions and beliefs about practical performance of atraumatic spinal needles. Therefore, we investigated the practical characteristics of atraumatic and traumatic spinal needles. An experimental setup with a fluid column was used with (1) a physiological NaCl 0.9 % solution and (2) a high protein content solution. Flow rates and duration of pressure measurements were measured using a traumatic needle and an atraumatic needle. The average flow rate differed less than 10 % between the two needle types with NaCl solution, and for the high protein solution the difference was even smaller. Time taken to perform accurate pressure measurements did not differ between the two needle types using NaCl 0.9 %, and was even slightly shorter for the atraumatic needle when using the high protein solution. Average flow rates and duration of pressure measurements are comparable between atraumatic spinal needles and traumatic needles. Therefore, these performance characteristics are no reason to favor traumatic needles over atraumatic needles.

Clinical fluctuations in MuSK myasthenia gravis are related to antigen-specific IgG4 instead of IgG1.

We studied the longitudinal relation between disease severity and titers of antigen-specific IgG subclasses in sera of patients with myasthenia gravis and antibodies to Muscle Specific Kinase (MuSK MG). Six patients were included of whom 55 samples had been collected during 2.5-13.4 years. Anti-MuSK antibodies were determined by ELISA and with a cell-based immunofluorescence assay. Disease severity was scored on a semi continuous scale. Only antigen-specific IgG4, and not IgG1, titers were significantly associated with disease severity in a linear mixed effect model (p = 0.036). Levels of IgG4 antibodies were above IgG1 in all samples except in one patient who went into clinical remission while switching from IgG4 to IgG1. The results support an important role for IgG4 in the pathogenesis of MuSK MG, in contrast to MG with anti-acetylcholine receptor antibodies.

The Lambert-Eaton myasthenic syndrome 1988-2008: a clinical picture in 97 patients.

BACKGROUND: Neuromuscular symptoms in patients with Lambert-Eaton myasthenic syndrome (LEMS) and a small cell lung cancer (SCLC) develop more rapidly than in LEMS patients without a SCLC. We studied how this clinical information, which is readily available at the first consultation, can be used to predict the presence of SCLC. PATIENTS AND METHODS: In our study we included 52 LEMS patients with SCLC and 45 non-tumor patients (NT-LEMS). We interviewed patients using a structured checklist and reviewed their clinical records. We compared frequency and onset of symptoms during the course of LEMS. RESULTS: In the first six months, over half the SCLC-LEMS patients had developed seven separate symptoms, while NT-LEMS patients developed only two symptoms. Proximal leg weakness and dry mouth were early symptoms in both groups. Rapid involvement of proximal arm muscles (p=0.0001), distal arm muscles (p=0.0037), distal leg muscles (p=0.0002), dysartria (p=0.0091) and the presence of erectile dysfunction (p=0.007) were found significantly more often in SCLC-LEMS patients in both cohorts. Cerebellar symptoms, although present in 9% of LEMS patients, were almost exclusively related to SCLC-LEMS. CONCLUSION: A rapidly progressive course of disease from onset in LEMS patients should raise a high suspicion of SCLC. Special attention should be paid to involvement of upper extremities, involvement of distal arm and distal leg muscles, to erectile dysfunction and probably ataxia in order to discriminate between SCLC-LEMS and NT-LEMS.

Utilization of sunglasses: A pilot study to examine a simple test for cognitive dysfunction.

OBJECTIVE: Utilization is an executive function disorder and implies an inappropriate response to external stimuli. The sunglasses test is a simple test to examine utilization by offering a pair of sunglasses to a patient without any instruction. PATIENTS AND METHODS: We performed a pilot study to examine the sunglasses test in 100 patients, of which 50 had cognitive symptoms and 50 did not have cognitive symptoms. When the patient put on the sunglasses, the test was considered positive. Cognitive dysfunction was based on the results of the MMSE, results of the clock test and neuropsychological examination (blinded). The final diagnosis was based on all results of the work-up (including MRI). RESULTS: Of the 50 patients with cognitive symptoms 30 had a positive test and 28 of them had cognitive dysfunction. Final diagnosis in most patients was Dementia due to probable Alzheimers disease, followed by Frontotemporal dementia. Seven of the 20 patients with a negative test also had cognitive dysfunction. None of the 50 patients without cognitive symptoms put on the sunglasses. Sensitivity of the sunglasses test to detect cognitive dysfunction was 80% and specificity was 97%, with a positive predictive value of 93%. CONCLUSION: Offering sunglasses is a simple test to screen for utilization. Putting on sunglasses without instruction to do so can be indicative for cognitive dysfunction and further cognitive evaluation should be considered. Future studies are needed in a larger group of patients and to determine the role of this test in different diseases with cognitive decline.

Olfactory dysfunction in behavioral variant frontotemporal dementia.

OBJECTIVE: Several neurodegenerative disorders show olfactory dysfunction. In patients with frontotemporal dementia (FTD), olfactory impairment is probably due to the involvement of the temporal and orbitofrontal lobes. We hypothesized that due to the disrupted areas in FTD, there would be an impairment in smell identification, differentiation and association. Moreover, we hypothesized that there would be a correlation between the severity of FTD and the severity of odor dysfunction. METHODS: In the current study, we compared odor identification, discrimination and association of nine patients with behavioral variant FTD with eleven healthy controls using the Brief Smell Identification Test and the Odor Perception and Semantics Battery. RESULTS: The results showed significant differences in the odor association test, but not in the identification or discrimination test. There was no correlation between disease severity and the performance in the odor tests. CONCLUSION: We showed impairment of odor association that is most likely due to disruption of specific associative areas involved in olfactory processing. Specifically, we propose that the impairment may well be due to disrupted areas in the temporal lobe and amygdala.

From VGKC to LGI1 and Caspr2 encephalitis: The evolution of a disease entity over time.

A wide variety of clinical syndromes has been associated with antibodies to voltage-gated potassium channels (VGKCs). Six years ago, it was discovered that patients do not truly have antibodies to potassium channels, but to associated proteins. This enabled the distinction of three VGKC-positive subgroups: anti-LGI1 patients, anti-Caspr2 patients and VGKC-positive patients lacking both antibodies. Patients with LGI1-antibodies have a limbic encephalitis, often with hyponatremia, and about half of the patients have typical faciobrachial dystonic seizures. Caspr2-antibodies cause a more variable syndrome of peripheral or central nervous system symptoms, almost exclusively affecting older males. Immunotherapy seems to be beneficial in patients with antibodies to LGI1 or Caspr2, stressing the need for early diagnosis. Half of the VGKC-positive patients lack antibodies to both LGI1 and Caspr2. This is a heterogeneous group of patients with a wide variety of clinical syndromes, raising the question whether VGKC-positivity is truly a marker of disease in these patients. Data regarding this issue are limited, but a recent study did not show any clinical relevance of VGKC-positivity in the absence of antibodies to LGI1 and Caspr2. The three VGKC-positive subgroups are essentially different, therefore, the lumping term 'VGKC-complex antibodies' should be abolished.

One-year follow-up of psychotherapy and pharmacotherapy for cocaine dependence. Delayed emergence of psychotherapy effects.

BACKGROUND: Neither the durability of brief ambulatory treatments for cocaine dependence nor the relative ability of psychotherapy vs pharmacotherapy to effect lasting change has been evaluated in well-controlled randomized trials. METHODS: We conducted a 1-year naturalistic follow-up of 121 ambulatory cocaine abusers who underwent psychotherapy (cognitive-behavioral relapse prevention or clinical management) and pharmacotherapy (desipramine hydrochloride or placebo) in a 2 x 2 design. Subjects were interviewed 1, 3, 6, or 12 months after the termination of a 12-week course of outpatient treatment. Eighty percent (n = 97) of the subjects who were randomized to treatment were followed up at least once. RESULTS: First, the effects of study treatments appeared durable over the follow-up; as for the full sample, measures of cocaine use indicated either improvement or no change over posttreatment levels. Second, abstinence during treatment was strongly associated with less cocaine use during follow-up. Third, random effects regression models indicated significant psychotherapy-by-time effects, suggesting a delayed improved response during follow-up for patients who received cognitive-behavioral relapse prevention compared with supportive clinical management. CONCLUSIONS: Our findings suggest a delayed emergence of the effects of cognitive-behavioral relapse prevention, which may reflect the subjects' implementation of the generalizable coping skills conveyed through that treatment. Moreover, these data underline the importance of conducting follow-up studies of substance abusers and other groups because delayed effects may occur after the cessation of short-term treatments.

HLA class I and II in Lambert-Eaton myasthenic syndrome without associated tumor.

Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder, in which antibodies against voltage-gated calcium channels located at nerve terminals cause muscle weakness and autonomic dysfunction. In approximately half of the patients the autoimmune process is initiated by a tumor. In the other half of patients no tumor is found and the etiology is unknown. The aims of this study were to investigate the strength of HLA-associations with nontumor LEMS (NT-LEMS) and to study the relation of HLA-haplotypes with age at onset of LEMS and other clinical features. Therefore, typing of HLA class I and II was performed in 19 patients with NT-LEMS, who were clinically evaluated. NT-LEMS was significantly associated with alleles of both HLA-class I (i.e. HLA-B8) as well as -class II (i.e. HLA-DR3 and -DQ2). HLA-B8+ patients had significantly younger age at onset of LEMS and tended to be female. This study shows that HLA-class I haplotype is associated with a distinct phenotype in NT-LEMS.

Network support for drinking, Alcoholics Anonymous and long-term matching effects.

AIMS: (1) To examine the matching hypothesis that Twelve Step Facilitation Therapy (TSF) is more effective than Motivational Enhancement Therapy (MET) for alcohol-dependent clients with networks highly supportive of drinking 3 years following treatment; (2) to test a causal chain providing the rationale for this effect. DESIGN: Outpatients were re-interviewed 3 years following treatment. ANCOVAs tested the matching hypothesis. SETTING: Outpatients from five clinical research units distributed across the United States. PARTICIPANTS: Eight hundred and six alcohol-dependent clients. INTERVENTION: Clients were randomly assigned to one of three 12-week, manually-guided, individual treatments: TSF, MET or Cognitive Behavioral Coping Skills Therapy (CBT). MEASUREMENTS: Network support for drinking prior to treatment, Alcoholics Anonymous (AA) involvement during and following treatment, percentage of days abstinent and drinks per drinking day during months 37-39. FINDINGS: (1) The a priori matching hypothesis that TSF is more effective than MET for clients with networks supportive of drinking was supported at the 3 year follow-up; (2) AA involvement was a partial mediator of this effect; clients with networks supportive of drinking assigned to TSF were more likely to be involved in AA; AA involvement was associated with better 3-year drinking outcomes for such clients. CONCLUSIONS: (1) In the long-term TSF may be the treatment of choice for alcohol-dependent clients with networks supportive of drinking; (2) involvement in AA should be given special consideration for clients with networks supportive of drinking, irrespective of the therapy they will receive.

Matching treatment focus to patient social investment and support: 18-month follow-up results.

Patients were randomly assigned to 1 of 3 treatments: brief broad-spectrum (BBS), extended relationship enhancement (ERE), or extended cognitive-behavioral (ECB). A hierarchical latent growth model was used to analyze the data of 188 patients (82%) followed for 18 months. ERE treatment was significantly more effective in increasing abstinence of patients entering treatment with a network unsupportive of abstinence or with a low level of investment in their network, whereas BBS treatment was more effective for patients with either (a) both a social network unsupportive of abstinence and a low level of network investment or (b) high investment in a network supportive of abstinence. ECB outcomes were neither as good as those matched nor as bad as those mismatched to the different exposures of relationship enhancement. This suggests that dose of relationship enhancement should be determined after assessing patient relationships.

Treatment settings for persons with alcoholism: evidence for matching clients to inpatient versus outpatient care.

This study compared inpatient, intensive outpatient, and standard outpatient treatment settings for persons with alcoholism and tested a priori hypotheses about the interaction of setting with client alcohol involvement and social network support for drinking. Participants (N = 192) were assigned randomly in cohorts to 1 of the 3 settings. The settings did not differ in posttreatment primary drinking outcomes, although inpatients had significantly fewer jail and residential treatment days combined than outpatients. Clients high in alcohol involvement benefited more from inpatient than outpatient care; the opposite was true at low alcohol involvement levels. Network drinking support did not moderate setting effects. Clients low in cognitive functioning also appeared to benefit more from inpatient than outpatient care. Improved outcomes might be achieved by matching degree of alcohol involvement and cognitive functioning to level of care.

Internal validity of Project MATCH treatments: discriminability and integrity.

Project MATCH (Matching Alcoholism Treatments to Client Heterogeneity) is a multisite collaborative project designed to evaluate patient-treatment interactions in alcoholism treatment. To evaluate whether major threats to the internal validity of the independent (treatment) variable in Project MATCH could be ruled out, we investigated several aspects of treatment integrity and discriminability. In this study, 1,726 alcohol-dependent participants at 10 sites were randomized to 3 treatments: cognitive-behavioral treatment (CBT), motivational enhancement therapy (MET), and 12-step facilitation (TSF). Participants received treatment either as outpatients or as aftercare following a more intensive inpatient or day hospital treatment. For both the outpatient and aftercare arms of the study, treatments were discriminable in that therapists implemented each of the treatments according to manual guidelines and rarely used techniques associated with comparison approaches. Participants received a high level of exposure to their study treatments, and the intended contrast in treatment dose between MET and the 2 more intensive treatments (CBT and TSF) was obtained. Alcoholics Anonymous involvement was significantly higher for participants assigned to TSF versus MET or CBT, whereas the treatments did not differ in utilization of other nonstudy treatments. Nonspecific aspects of treatment such as therapist skillfulness and level of the therapeutic alliance were comparable across treatment conditions.

Issues in the development of client-treatment matching hypotheses.

This article discusses observations and insights that were gained in the course of critiquing the a priori client-treatment matching hypothesis that were developed for Project MATCH. A matching taxonomy is offered that differentiates eight types of ordinal and disordinal interactions and discusses their clinical and substantive implications. Previously reported alcohol treatment studies are used to illustrate many of these. Various issues in matching studies, such as power versus complexity, prediction versus explanation, matches versus mismatches and capitalization versus compensation, are discussed. Selective issues in choosing treatment and client-matching variables as they affect matching hypotheses are also addressed. The importance of developing a putative "causal chain" for testing the theory underlying matching processes is explicated and a procedure for testing this causal chain is outlined.

Ensuring balanced distribution of prognostic factors in treatment outcome research.

In comparative or matching research involving two or more treatments, the equivalence of the patient groups is of critical importance. In the past, equivalence has either been imposed by matching or balancing, or has been assured statistically by randomization. Matching and balancing, while useful in many contexts, nonetheless have important limitations, as does simple randomization. In recent years, a new tool has been developed that represents a compromise between balancing and randomization. This method, urn randomization, gives clinical investigators new options for improving the credibility of studies at a relatively modest cost. Urn randomization is randomization that is systematically based in favor of balancing. It can be used with several covariates, both marginally and jointly, producing optimal multivariate equivalence of treatment groups for large sample sizes. It preserves randomization as the primary basis for assignment to treatment and is less susceptible to experimenter bias or manipulation of the allocation process by staff than is balancing. Disadvantages include the fact that it is more difficult to implement, and that it violates the simple probability model of simple randomization. A number of research studies on addictions, including client-treatment matching trials, have used urn randomization. A summary of the mechanics of urn randomization is presented, and guidelines for its use in treatment studies are discussed.

Alternative analytical methods for detecting matching effects in treatment outcomes.

Project MATCH presented a unique opportunity for a team of statisticians, data analysts and content experts to come together and explore the strengths and weaknesses of the application of various statistical models to the data of the type being collected in this large trial. The following models were evaluated: multilevel models, event history models, multiple were structural equation modeling, time series models, ordinal repeated measures designs and generalized estimating equations. No one model was found to be the perfect solution and each seemed to have something to recommend it. Future research on these methods will shed light on many issues raised. It is hoped that alcohol researchers will find useful guidelines within this chapter as they plan and carry out their studies.

Classical analytical methods for detecting matching effects on treatment outcome.

This article presents a classical approach for analyzing repeated measures designs with specific application to treatment matching studies. The generic treatment matching hypothesis is formulated under the multivariate general linear model, transforming the dependent variables to account for the repeated measures structure of the data. Issues of primary importance in the use of this approach (such as correcting for inflated Type I error and robustness of statistical tests to parametric assumptions) are discussed. The article concludes with an assessment of the strengths and weaknesses of this approach compared with alternative approaches.

Paraparesis after lumbar puncture in a male with leukemia.

A diagnostic lumbar puncture was performed in a 12-year-old male with acute lymphoblastic leukemia. Because of thrombocytopenia (platelet count 42,000/mm(3)), a platelet transfusion was given immediately before the lumbar puncture. However, the platelet count was not re-examined. The patient developed progressive paraparesis shortly after the lumbar puncture. Magnetic resonance imaging revealed an extensive spinal subdural hematoma from the T2 to S2 level. This case report illustrates the sometimes dramatic consequences of lumbar puncture in patients with childhood leukemia. Guidelines for the examination of the platelet count and correction of thrombocytopenia before lumbar puncture are discussed.

An initial evaluation of the psychosocial dimensions of the American Society of Addiction Medicine criteria for inpatient versus intensive outpatient substance abuse rehabilitation.

OBJECTIVE: The American Society of Addiction Medicine (ASAM) criteria were developed as guidelines for the placement of substance abuse patients in appropriate levels of care. Although the ASAM criteria are widely used, little is known about their validity. In this study, we evaluated the predictive validity of the psychosocial dimensions of the ASAM criteria for inpatient versus intensive outpatient rehabilitation. METHOD: The psychosocial dimensions of the ASAM criteria were first operationalized with instruments with proven reliability and validity. The criteria were then used to determine whether cocaine (n = 159) and alcohol (n = 133) dependent male patients in inpatient and intensive outpatient rehabilitation programs were correctly "matched" to the level of care they received. The patients were followed up at 3, 6 and 12 months postrehabilitation, and outcomes of "matched" and "mismatched" patients were compared in a number of ways. RESULTS: Alcohol and cocaine patients who were correctly matched to treatment according to ASAM did not have significantly better outcomes than those who were mismatched. Furthermore, a more focused analysis generated no evidence that alcohol patients who met ASAM criteria for inpatient care had better outcomes in that setting than in intensive outpatient treatment. Among cocaine patients who met ASAM inpatient criteria, inpatient care produced marginally better short-term outcomes on most measures, although these results did not reach statistical significance. CONCLUSIONS: These results suggest that the psychosocial dimensions of the ASAM criteria for inpatient treatment are probably too broad and are therefore in need of further refinement, particularly for alcohol patients. However, all patients were male veterans without acute medical problems serious enough to warrant inpatient care or histories of psychosis, and the majority were of lower socioeconomic status. It is not clear to what extent the results would generalize to substance abusers with other characteristics.