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Biomedical subjects

Kathleen Hawker

Publications and source records attributed to Kathleen Hawker.

9 recordsLinked to original sources

Urodynamic distinctions between idiopathic detrusor overactivity and detrusor overactivity secondary to multiple sclerosis.

OBJECTIVES: To evaluate the urodynamic characteristics of neurogenic detrusor overactivity (NDO) secondary to multiple sclerosis (MS) compared with idiopathic DO (IDO) to determine whether urodynamic distinctions could differentiate the different etiologies of DO. METHODS: The urodynamic characteristics of DO in women with MS (n = 54) were compared with the overactive contractions found in women with lower urinary tract symptoms and IDO (n = 42). Among other parameters, the amplitude of the first overactive contraction, maximal detrusor contraction, and threshold volume for the first overactive contraction were evaluated to assess the DO severity. A sensitivity analysis using cutoff values determined from those urodynamic parameters that differed between the patient groups is presented. RESULTS: The amplitude of the first overactive contraction was statistically greater in the patients with MS and NDO compared with patients with IDO (28.3 cm H2O versus 20.5 cm H2O, P = 0.003), as was the maximal detrusor contraction (46.4 cm H2O versus 30.8 cm H2O, P = 0.002). The threshold volume for DO was greater among patients with NDO (186.8 mL versus 150.5 mL, P = 0.037), likely secondary to the elevated postvoid residual urine volume noted among patients with MS (P = 0.049). Using a cutoff value of 30 cm H2O for amplitude of the first overactive contraction achieved a positive predictive value of 88% for identifying MS in our data set. CONCLUSIONS: The urodynamic characteristics of NDO differed significantly from those of IDO. Additional investigation is required to determine whether these differences are due to neurogenic influences directly on the detrusor muscle through aberrant innervation or by other mechanisms, such as enhanced outlet resistance during voiding.

Adult↗

Therapeutic considerations for disease progression in multiple sclerosis: evidence, experience, and future expectations.

In the management of patients with multiple sclerosis (MS), providers are all faced with the highly formidable challenge of ascertaining whether, and to what degree, disease-modifying therapy is effective in the individual patient. While much has been learned in randomized, controlled clinical trials, we cannot simply extrapolate the outcomes of these initiatives and apply them to the care of a single patient. In the future, the application of pharmacogenetic techniques, proteomics, and microarray analysis will yield novel profiling information on individual patients that will substantially refine the specific therapeutic questions of relevance: (1) What is the best treatment for an individual patient? (2) Which patients require intensive therapeutic combination regimens to optimize control of the disease process? (3) What are the appropriate drug dosing targets for an individual patient? and (4) Which patients will be predisposed to the development of drug-related adverse events? Such data may provide a novel variable of drug responsiveness that will mandate its inclusion into the process of covariate analyses for clinical trials.

Disease Progression↗

Effect of rituximab on the peripheral blood and cerebrospinal fluid B cells in patients with primary progressive multiple sclerosis.

BACKGROUND: Rituximab, an anti-CD20 monoclonal antibody that depletes CD20(+) B cells, has demonstrated efficacy in peripheral neurological diseases. Whether this efficacy can be translated to neurological diseases of the central nervous system with possible autoimmune B-cell involvement remains unknown. OBJECTIVE: To determine the effect of rituximab on cerebrospinal fluid B cells in patients with multiple sclerosis. DESIGN: Four patients with primary progressive multiple sclerosis were treated with rituximab. Cerebrospinal fluid and peripheral blood B-cell subsets were identified by flow cytometry from each patient before and after rituximab treatment. RESULTS: The B cells in cerebrospinal fluid were not as effectively depleted as their peripheral blood counterparts. Rituximab treatment temporarily suppressed the activation state of B cells in cerebrospinal fluid. The residual B cells underwent expansion after rituximab treatment. CONCLUSION: The effect(s) of rituximab on the cerebrospinal fluid B-cell compartment is limited in comparison with the effect(s) on the B cells in the periphery, but this finding will need to be confirmed in a larger group of MS patients.

Adult↗

Incidence of upper tract abnormalities in patients with neurovesical dysfunction secondary to multiple sclerosis: analysis of risk factors at initial urologic evaluation.

OBJECTIVES: To determine the incidence of upper tract abnormalities on renal ultrasonography in patients with multiple sclerosis (MS) referred for urologic evaluation, as well as to identify any risk factors present on the basis of the historical information and urodynamic findings. METHODS: Data were derived from all patients with MS referred to the neurourology clinic during a 4-year period. The database was specifically queried for patients found to have upper tract abnormalities on screening renal ultrasonography. Demographic parameters, as well as laboratory values (creatinine) and urodynamic results, were evaluated for risk factors associated with abnormal upper tract findings. RESULTS: Of the 113 patients referred and evaluated, 66 completed both urodynamic testing and renal ultrasonography. Eleven (16.7%) had abnormal ultrasound findings, with focal caliectasis the most common finding. No demographic parameter (age, sex, time since MS diagnosis, MS pattern) was associated with a greater likelihood of abnormal renal ultrasonography on univariate analysis. Neither serum creatinine nor any urodynamic finding (including the presence of dyssynergia or the threshold and amplitude of detrusor overactivity) was associated with abnormal renal ultrasound findings. CONCLUSIONS: No patients in our series had any indication of obstructive uropathy more severe than mild hydronephrosis. Of the 16.7% of patients with any abnormal findings, most were noted to have minor caliectasis, likely to be of little clinical significance. Although no factors identifying patients at risk of renal abnormalities at presentation were found, ongoing evaluation of patients with baseline findings will serve to identify those at risk of progression.

Diagnostic Techniques, Urological↗

Multiple sclerosis.

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Disease Progression↗

Levetiracetam for phasic spasticity in multiple sclerosis.

BACKGROUND: Spasticity is a common and debilitating symptom of multiple sclerosis (MS). Current treatments are effective, but may be difficult to tolerate for many patients. OBJECTIVE: To determine if levetiracetam, a second-generation antiepileptic drug, may be useful for the treatment of spasticity in MS. METHODS: A retrospective medical record review of patients attending the Multiple Sclerosis Program at the University of Texas, Southwestern Medical Center at Dallas was performed. A series of 12 patients who had been treated with levetiracetam for spasticity was identified. Most of the patients were female (10/11), and the mean age was 41.0 years. The main outcome measure was a change in Penn spasm score or modified Ashworth score. Both scores are measured on a scale of 0 to 4. RESULTS: The Penn Spasm score (a measure of phasic spasticity) was decreased for all patients following treatment with levetiracetam. The mean +/- SD Penn Spasm score was 2.7 +/- 0.65 at baseline and decreased to 0.9 +/- 0.29 at follow-up. There was no change in modified Ashworth scores (a measure of tonic spasticity). Five patients reported adverse events; 1 patient discontinued treatment owing to an adverse event (edema). Three patients incidentally reported improvements in neuropathic pain. CONCLUSIONS: Levetiracetam was effective for reducing phasic spasticity but not tonic spasticity in this 12-patient case series. The drug was well tolerated and therefore shows promise as a treatment for phasic spasticity. Large, well-controlled trials are needed to confirm these findings.

Adult↗

Disease-modifying therapy in multiple sclerosis: strategies for optimizing management.

BACKGROUND: The objective for this article is to highlight several challenges faced by patients and providers in the utilization of disease-modifying agent (DMA) therapy in multiple sclerosis (MS) and to offer practical management strategies that can effectively mitigate or even prevent limiting adverse reactions and enhance treatment compliance. REVIEW SUMMARY: Our discussion will be limited to the use of interferon beta1a (Avonex, Rebif), interferon beta1b (Betaseron), and glatiramer acetate (Copoxane) as these are the primary agents used in the United States for primary disease-modifying therapy in relapsing forms of MS. Some of the recommendations contained herein are derived from evidence-based studies, while others are contingent upon our collective clinical experiences. At the University of Texas Southwestern Medical Center at Dallas and Texas Neurology in Dallas we actively follow approximately 5000 MS patients. The majority of our patients with relapsing-remitting MS (RRMS) or secondary progressive MS (SPMS) are treated with one of the currently available DMAs. Our experience with these patients, and the challenges they face in continuing long-term treatment, constitutes the basis of our proposed treatment strategies. As part of this effort we formulated an assessment and intervention instrument that can be used in the clinic and by telephone to enhance compliance and minimize adverse events. CONCLUSION: A comprehensive treatment approach to the utilization of disease-modifying therapy in MS can serve to optimize the management of our patients and effectively meet the challenges that arise during the course of treatment.

Journal Article↗

Mycophenolate mofetil in multiple sclerosis.

OBJECTIVE: To describe experience with the use of mycophenolate mofetil (MMF) in the treatment of multiple sclerosis (MS). BACKGROUND: MMF is a potent immunosuppressant that is a selective inhibitor of inosine 5'-monophosphate dehydrogenase type II, the enzyme responsible for the de novo synthesis of the purine nucleotide guanine within activated T and B lymphocytes and macrophages. METHODS: A retrospective review of experience in treating 79 MS patients with MMF (61 with secondary progressive, 14 with relapsing-remitting, and 4 with primary progressive MS) in the authors' MS center. RESULTS: In most cases, MMF was added as adjunctive therapy in patients already being treated with either interferon-beta (n = 44) or glatiramer acetate (n = 20). Fifteen patients not able to use interferon or glatiramer acetate were treated with MMF monotherapy. Seventy percent of the patients continued MMF therapy. Eight patients discontinued therapy because of side effects, 7 patients continued to exhibit evidence of disease progression, 4 were denied insurance coverage, 2 were lost to follow-up, and 1 patient had an elevation of hepatic transaminases that resolved on discontinuation of MMF. One patient discontinued MMF therapy secondary to cytomegalovirus diarrhea. CONCLUSION: MMF was well tolerated by the majority of patients treated. While these clinical observations were uncontrolled, the clinical course of MS was either unchanged or subjectively improved in many of the treated patients. A randomized controlled trial of MMF in MS, either as monotherapy or in conjunction with interferon or glatiramer acetate, appears warranted.

Adjuvants, Immunologic↗