Treatment of spasticity.

Spasticity is characterized by an enhanced size and reduced threshold for activation of stretch reflexes and is associated with "positive signs" such as clonus and spasms, as well as "negative features" such as paresis and a loss of automatic postural responses. Spasticity develops over time after a lesion and can be associated with reduced speed of movement, cocontraction, abnormal synergies, and pain. Spasticity is caused by a combination of damage to descending tracts, reductions in inhibitory activity within spinal cord circuits, and adaptive changes within motoneurons. Increased tone, hypertonia, can also be caused by changes in passive stiffness due to, for example, increase in connective tissue and reduction in muscle fascicle length. Understanding the cause of hypertonia is important for determining the management strategy as nonneural, passive causes of stiffness will be more amenable to physical rather than pharmacological interventions. The management of spasticity is determined by the views and goals of the patient, family, and carers, which should be integral to the multidisciplinary assessment. An assessment, and treatment, of trigger factors such as infection and skin breakdown should be made especially in people with a recent change in tone. The choice of management strategies for an individual will vary depending on the severity of spasticity, the distribution of spasticity (i.e., whether it affects multiple muscle groups or is more prominent in one or two groups), the type of lesion, and the potential for recovery. Management options include physical therapy, oral agents; focal therapies such as botulinum injections; and peripheral nerve blocks. Intrathecal baclofen can lead to a reduction in required oral antispasticity medications. When spasticity is severe intrathecal phenol may be an option. Surgical interventions, largely used in the pediatric population, include muscle transfers and lengthening and selective dorsal root rhizotomy.

Prevalence and incidence of chronic conditions among adults with cerebral palsy: A systematic review and meta-analysis.

AIM: To assess the prevalence and incidence of chronic conditions among adults with cerebral palsy (CP) and compare them to the prevalence and incidence among adults without CP. METHOD: We searched MEDLINE and Embase for studies reporting the prevalence or incidence of one or more chronic conditions among adults with CP. Two independent reviewers screened titles, abstracts, and full-text articles. Two independent reviewers extracted data relating to prevalence and incidence and appraised study quality. We performed random-effects meta-analyses to pool prevalence and incidence. RESULTS: We identified 69 studies; 65 reported the prevalence of 53 conditions and 13 reported the incidence of 21 conditions. At least 20% of adults had the following conditions: depression (21%); anxiety (21%); mood affective disorders (23%); asthma (24%); hypertension (26%); epilepsy (28%); urinary incontinence (32%); malnutrition (38%); and scoliosis (46%). Adults with CP were more likely to have type 2 diabetes, anxiety, bipolar disorder, depression, schizophrenia, hypertension, ischaemic heart disease, stroke, cerebrovascular disease, asthma, liver disease, osteoarthritis, osteoporosis, underweight, and chronic kidney disease than adults without CP. INTERPRETATION: These data from 18 countries, which provide an international perspective, may be used to promote awareness, identify targets for intervention, and inform the development of appropriate supports for adults with CP.

Intrathecal baclofen pumps: what the neurologist needs to know.

Increasing numbers of patients have an intrathecal baclofen pump implanted as part of spasticity management. Neurologists may be asked about the management of these devices when patients attend emergency departments for unrelated illnesses. Occasionally, the intrathecal baclofen system itself will directly lead to an acute presentation. Furthermore, the presence of an intrathecal baclofen pump needs consideration when requesting investigations, particularly MR imaging. This review aims to increase understanding of intrathecal baclofen treatment, highlighting serious complications and outlining considerations for routine investigations. Neurologists may still need advice from the intrathecal baclofen specialist team.

Functional electrical stimulation to aid walking in patients with adrenomyeloneuropathy: A case study and observational series.

Adrenomyeloneuropathy (AMN) is a rare inherited condition where affected individuals develop slowly progressive spastic paraparesis with a gradual decline in walking ability. There is no cure for AMN and treatment focuses on supportive measures and aids. One treatment option is functional electrical stimulation (FES), a treatment, approved by The National Institute for Health and Care Excellence (NICE), for managing foot drop in upper motor neuron disorders. Limited evidence exists for its use in AMN patients. We describe the effects of FES in an individual case and more broadly within a cohort of 21 patients successfully treated with FES. Patients with AMN referred for FES typically report frequent falls (71%) and foot drop (57%) as the most common barriers to walking. When using FES, walking speed at baseline (0.70 m/s [SD = 0.2]) was maintained at the 2-year review (0.68 m/s [SD = 0.2]) with a persistent orthotic effect (improvement in walking speed when device on vs. off) seen from wearing FES over the same 2-year period (11%-19%). Patient walking satisfaction (visual analogue scale: 0 - very dissatisfied; 10 - very satisfied) was also greater when comparing no-FES versus FES over the same period (Year 1: 2.5 vs. 7.7; Year 2: 2.1 vs. 6.1). FES is not effective in all patients. Twelve patients referred found no benefit from the device; although there was no clear evidence, this was related to the degree of AMN associated peripheral neuropathy. However, FES is a safe, cost-effective treatment option and should be considered, along with assessment in a multidisciplinary clinic, for all AMN patients with walking difficulties.

European expert consensus on improving patient selection for the management of disabling spasticity with intrathecal baclofen and/or botulinum toxin type A.

OBJECTIVE: To develop an algorithm for the selection of adults with disabling spasticity for treatment with intrathecal baclofen (ITB) and/or botulinum toxin type A (BoNT A). METHODS: A European Advisory Board of 4 neurologists and 4 rehabilitation specialists performed a literature review on ITB and BoNT A treatment for disabling spasticity. An online survey was sent to 125 physicians and 13 non-physician spasticity experts. Information on their current clinical practice and level of agreement on proposed selection criteria was used to inform algorithm design. Consensus was considered reached when ≥75% of respondents agreed or were neutral. RESULTS: A total of 79 experts from 17 countries completed the on-line survey (57%). Agreement was reached that patients with multi-segmental or generalized disabling spasticity refractory to oral drugs are the best candidates for ITB (96.1% consensus), while those with focal/segmental disabling spasticity are ideal candidates for BoNT A (98.7% consensus). In addition the following are good candidates for ITB (% consensus): bilateral disabling spasticity affecting lower limbs only (97.4%), bilateral (100%) or unilateral (90.9%) disabling spasticity affecting lower limbs and trunk, and unilateral or bilateral disabling spasticity affecting upper and lower extremities (96.1%). CONCLUSION: This algorithm will support the management of adult patients with disabling spasticity by aiding patient selection for ITB and/or BoNT A treatments.

Early Convalescent Plasma for High-Risk Outpatients with Covid-19.

BACKGROUND: Early administration of convalescent plasma obtained from blood donors who have recovered from coronavirus disease 2019 (Covid-19) may prevent disease progression in acutely ill, high-risk patients with Covid-19. METHODS: In this randomized, multicenter, single-blind trial, we assigned patients who were being treated in an emergency department for Covid-19 symptoms to receive either one unit of convalescent plasma with a high titer of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or placebo. All the patients were either 50 years of age or older or had one or more risk factors for disease progression. In addition, all the patients presented to the emergency department within 7 days after symptom onset and were in stable condition for outpatient management. The primary outcome was disease progression within 15 days after randomization, which was a composite of hospital admission for any reason, seeking emergency or urgent care, or death without hospitalization. Secondary outcomes included the worst severity of illness on an 8-category ordinal scale, hospital-free days within 30 days after randomization, and death from any cause. RESULTS: A total of 511 patients were enrolled in the trial (257 in the convalescent-plasma group and 254 in the placebo group). The median age of the patients was 54 years; the median symptom duration was 4 days. In the donor plasma samples, the median titer of SARS-CoV-2 neutralizing antibodies was 1:641. Disease progression occurred in 77 patients (30.0%) in the convalescent-plasma group and in 81 patients (31.9%) in the placebo group (risk difference, 1.9 percentage points; 95% credible interval, -6.0 to 9.8; posterior probability of superiority of convalescent plasma, 0.68). Five patients in the plasma group and 1 patient in the placebo group died. Outcomes regarding worst illness severity and hospital-free days were similar in the two groups. CONCLUSIONS: The administration of Covid-19 convalescent plasma to high-risk outpatients within 1 week after the onset of symptoms of Covid-19 did not prevent disease progression. (SIREN-C3PO ClinicalTrials.gov number, NCT04355767.).

The effectiveness of peroneal nerve functional electrical simulation for the reduction of bradykinesia in Parkinson's disease: A feasibility study for a randomised control trial.

OBJECTIVES: To assess the feasibility of a multi-site randomised controlled trial to evaluate the effect of functional electrical stimulation on bradykinesia in people with Parkinson's disease. DESIGN: A two-arm assessor blinded randomised controlled trial with an 18 weeks intervention period and 4 weeks post-intervention follow-up. SETTING: Two UK hospitals; a therapy outpatient department in a district general hospital and a specialist neuroscience centre. PARTICIPANTS: A total of 64 participants with idiopathic Parkinson's disease and slow gait <1.25 ms-1. INTERVENTIONS: Functional electrical stimulation delivered to the common peroneal nerve while walking in addition to standard care compared with standard care alone. MAIN MEASURES: Feasibility aims included the determination of sample size, recruitment and retention rates, acceptability of the protocol and confirmation of the primary outcome measure. The outcome measures were 10 m walking speed, Unified Parkinson's Disease Rating Scale (UPDRS), Mini Balance Evaluation Systems Test, Parkinson's Disease Questionnaire-39, EuroQol 5-dimension 5-level, New Freezing of Gait questionnaire, Falls Efficacy Score International and falls diary. Participants opinion on the study design and relevance of outcome measures were evaluated using an embedded qualitative study. RESULTS: There was a mean difference between groups of 0.14 ms-1 (CI 0.03, 0.26) at week 18 in favour of the treatment group, which was maintained at week 22, 0.10 ms-1 (CI -0.05, 0.25). There was a mean difference in UPDRS motor examination score of -3.65 (CI -4.35, 0.54) at week 18 which was lost at week 22 -0.91 (CI -2.19, 2.26). CONCLUSION: The study design and intervention were feasible and supportive for a definitive trial. While both the study protocol and intervention were acceptable, recommendations for modifications are made.

Reducing Intrathecal Baclofen Related Infections: Service Evaluation and Best Practice Guidelines.

OBJECTIVES: Intrathecal baclofen (ITB) pumps are an effective treatment for spasticity; however infection rates have been reported in 3-26% of patients in the literature. The multidisciplinary ITB service has been established at The National Hospital for Neurology and Neurosurgery, UCLH, Queen Square, London for over 20 years. Our study was designed to clarify the rate of infection in our ITB patient cohort and secondly, to formulate and implement best practice guidelines and to determine prospectively, whether they effectively reduced infection rates. METHODS: Clinical record review of all patients receiving ITB pre-intervention; January 2013-May 2015, and following practice changes; June 2016-June 2018. RESULTS: Four of 118 patients receiving ITB during the first time period (3.4%, annual incidence rate of infection 1.4%) developed an ITB-related infection (three following ITB pump replacement surgery, one after initial implant). Infections were associated with 4.2% of ITB-related surgical procedures. Three of four pumps required explantation. Following change in practice (pre-operative chlorhexidine skin wash and intraoperative vancomycin wash of the fibrous pocket of the replacement site), only one of 160 ITB patients developed infection (pump not explanted) in the second time period (0.6%, annual incidence rate 0.3%). The infection rate related to ITB surgical procedures was 1.1%. In cases of ITB pump replacement, the infection rate was reduced to 3.3% from 17.6%. CONCLUSIONS: This study suggests that a straightforward change in clinical practice may lower infection rates in patients undergoing ITB therapy.

Innovative treatment of clinically diagnosed meniscal tears: a randomized sham-controlled trial of the Mulligan concept 'squeeze' technique.

Objective: The purpose of this study was to assess the effects of the Mulligan Concept (MC) 'squeeze' technique compared to a sham technique in participants with a clinically diagnosed meniscal tear.Methods: A multi-site randomized sham-controlled trial of participants (n = 23), aged 24.91 ± 12.09 years, with a clinically diagnosed meniscal tear were equally and randomly divided into two groups. Groups received a maximum of six treatments over 14 days. Patient outcomes included the numeric pain rating scale (NRS), patient-specific functional scale (PSFS), the disablement in the physically active (DPA) scale and the knee injury osteoarthritis outcome score. Data were analysed using univariate ANOVA, univariate ANCOVA, and descriptive statistics.Results: All participants in the MC 'squeeze' group met the discharge criteria of ≤2 points on the NRS, ≥9 points on the PSFS, and ≤34 points or ≤23 on the DPA Scale for chronic or acute injuries, respectively within the treatment intervention timeframe. A significant difference was found in favor of the MC 'squeeze' technique in PSFS scores (F(1, 21) = 4.40, p = .048, partial eta squared = .17, observed power = .52) and in DPA Scale scores (F(1, 21) = 7.46, p = .013, partial eta squared = .27, observed power = .74).Discussion: The results indicate the MC 'squeeze' technique had positive effects on patient function and health-related quality of life over a period of 14 days and was clinically and statistically superior to the sham treatment. Further investigation of the MC 'squeeze' technique is warranted.

TREATING GROIN AND HIP FLEXOR PAIN USING PRIMAL REFLEX RELEASE TECHNIQUE™: A CASE SERIES.

BACKGROUND AND PURPOSE: The nervous system plays a significant role in groin/hip flexor pain which is a common complaint in the active population. Patient examinations that lack consideration of the nervous system's involvement may result in chronic pain and dysfunctional breathing patterns due to continuously excited (also known as "up-related") primal reflexes. Primal Reflex Release Technique™ (PRRT™) is a novel treatment paradigm that was designed to calm primal reflexes from their excitatory state. The purpose of this case series was to describe the effects of down-regulating primal reflexes using PRRT™ on pain, function, and breathing pattern dysfunction in subjects who presented with groin and hip flexor pain and exhibited hyperesthesia to TriggerRegions™ in areas of respiration. CASE DESCRIPTIONS: Six subjects with acute groin and/or hip flexor pain were examined using a battery of tests including muscle integrity strength and range-of-motion (ROM) measurements, special orthopedic tests, breathing functionality and PRRT™ rib palpation assessments. If subjects were determined to be potential PRRT™ responders through PRRT™ rib palpation assessments, the technique was performed according to PRRT™ guidelines. Outcome measures including the Numeric Pain Rating Scale (NPRS), Patient Specific Functional Scale (PSFS), the Global Rating of Change (GRoC) Scale, and the Disability in the Physically Active (DPA) Scale were collected to determine the effects of the treatment. OUTCOMES: All subjects demonstrated full resolution of pain as reported on the Numeric Pain Rating Scale, and the change was statistically (p = 0.001) and clinically significant. All subjects returned to optimal function as reported on the Patient Specific Functional Scale, and the change was both clinically (minimal detectable change) and statistically significant (p = 0.001). All subjects returned to normal breathing function as observed through the seated assessment of lateral expansion test. The number of treatments (mean = 1.83 ± 1.16) and time to the resolution of symptoms was minimal (mean = 2.833 ± 2.56 days). DISCUSSION: By assessing and treating abnormal breathing patterns, postulated to be a result of a sustained excitatory nervous system, subjects returned to full activity, without pain, in less than three days. After a two-week follow-up, subjects remained functionally pain free. Considering the state of the nervous system in the presentation of musculoskeletal pain and not focusing all treatment on local muscle structures may be beneficial. A multifaceted assessment approach is needed to determine other pain factors. LEVEL OF EVIDENCE: Level 4.

Improvement in overactive bladder symptoms in patients using functional electrical stimulation of the common peroneal nerve for walking.

OBJECTIVE: Functional electrical stimulation is used to improve walking speed and reduces falls in people with upper motor neurone foot-drop. Following anecdotal observations of changes in bladder symptoms, an observational study was performed to explore this association further. DESIGN: A total of 47 consecutive patients attending for setup with functional electrical stimulation during a six-month period were asked to complete a questionnaire assessing bladder symptoms (ICIQ-OAB (International Consultation on Incontinence Questionnaire Overactive Bladder)) at baseline and three months during routine appointments. SUBJECTS: In all, 35 (75%) had multiple sclerosis and the other 12 subjects had a total of 9 diagnoses including 3 with stroke. Other conditions included cerebral palsy, motor neurone disease, hereditary spastic paraparesis, meningioma and spinocerebellar ataxias. RESULTS: Improvement in overactive bladder symptoms was not significant in the whole cohort, however, was significant in patients with multiple sclerosis ( n = 35; mean change in ICIQ-OAB score 1.0, P = 0.043). Specifically, significant improvements were seen in urgency and urge incontinence in multiple sclerosis patients. There was a significant negative correlation of moderate strength within the multiple sclerosis cohort between baseline walking speed and subsequent change in ICIQ-OAB score (correlation coefficient of r = -0.40, P = 0.046). Thus, greater changes in bladder symptoms were seen with lower baseline walking speeds. CONCLUSION: The results of this exploratory study suggest that functional electrical stimulation use does improve overactive bladder symptoms in people with multiple sclerosis. Further exploration is needed to study this association and explore whether the mechanism is similar to that of percutaneous tibial nerve stimulation, a recognized treatment for the overactive bladder.

Using the MyoKinesthetic System to Treat Bilateral Chronic Knee Pain: A Case Study.

OBJECTIVE: The purpose of this case study was to report the effects of the MyoKinesthetic (MYK) system on pain, functional ability, and psychosocial well-being of a 20-year-old female collegiate softball athlete diagnosed with chronic bilateral knee pain associated with osteoarthritis. CLINICAL FEATURES: The patient presented with bilateral chronic knee pain lasting more than 2 years. A clinical examination and radiographic imaging revealed chondromalacia and the beginning stages of osteoarthritis of the knee. No other comorbidities were noted. INTERVENTION AND OUTCOME: The patient received 4 treatments with the MYK system over 2 weeks. Treatments 1 through 3 were directed at the S1 nerve root; the fourth treatment was directed at the L4 nerve root. Outcome measures included the Numeric Pain Scale, the Patient-Specific Functional Scale, and the Disability in the Physically Active Scale. Pain, function, and quality of life were measured collectively using the Knee Injury and Osteoarthritis Outcome Score. The patient experienced clinical improvements (minimal clinical important differences, minimal detectable changes) for all outcome measures, with the exception of the quality-of-life subscale within the Knee Injury and Osteoarthritis Outcome Score. CONCLUSIONS: The patient in this case study reported a decrease in pain and an increase in function during the course of 4 treatments, which were administered over 14 days and in accordance to the MYK guidelines. Traditional treatment guidelines typically recommend 8 weeks for positive effects to manifest. Manual therapy techniques, such the MYK system, may be a viable treatment option for patients with osteoarthritis of the knee.

AN ALTERNATIVE APPROACH TO THE TREATMENT OF MENISCAL PATHOLOGIES: A CASE SERIES ANALYSIS OF THE MULLIGAN CONCEPT "SQUEEZE" TECHNIQUE.

BACKGROUND: Partial meniscectomy does not consistently produce the desired positive outcomes intended for meniscal tears lesions; therefore, a need exists for research into alternatives for treating symptoms of meniscal tears. The purpose of this case series was to examine the effect of the Mulligan Concept (MC) "Squeeze" technique in physically active participants who presented with clinical symptoms of meniscal tears. DESCRIPTION OF CASES: The MC "Squeeze" technique was applied in five cases of clinically diagnosed meniscal tears in a physically active population. The Numeric Pain Rating Scale (NRS), the Patient Specific Functional Scale (PSFS), the Disability in the Physically Active (DPA) Scale, and the Knee injury and Osteoarthritis Outcomes Score (KOOS) were administered to assess participant pain level and function. OUTCOMES: Statistically significant improvements were found on cumulative NRS (p ≤ 0.001), current NRS (p ≤ 0.002), PSFS (p ≤ 0.003), DPA (p ≤ 0.019), and KOOS (p ≤ 0.002) scores across all five participants. All participants exceeded the minimal clinically important difference (MCID) on the first treatment and reported an NRS score and current pain score of one point or less at discharge. The MC "Squeeze" technique produced statistically and clinically significant changes across all outcome measures in all five participants. DISCUSSION: The use of the MC "Squeeze" technique in this case series indicated positive outcomes in five participants who presented with meniscal tear symptoms. Of importance to the athletic population, each of the participants continued to engage in sport activity as tolerated unless otherwise required during the treatment period. The outcomes reported in this case series exceed those reported when using traditional conservative therapy and the return to play timelines for meniscal tears treated with partial meniscectomies. LEVELS OF EVIDENCE: Level 4.

Cerebral palsy.

Cerebral palsy has always been known as a disorder of movement and posture resulting from a non-progressive injury to the developing brain; however, more recent definitions allow clinicians to appreciate more than just the movement disorder. Accurate classification of cerebral palsy into distribution, motor type and functional level has advanced research. It also facilitates appropriate targeting of interventions to functional level and more accurate prognosis prediction. The prevalence of cerebral palsy remains fairly static at 2-3 per 1000 live births but there have been some changes in trends for specific causal groups. Interventions for cerebral palsy have historically been medical and physically focused, often with limited evidence to support their efficacy. The use of more appropriate outcome measures encompassing quality of life and participation is helping to deliver treatments which are more meaningful for people with cerebral palsy and their carers.

Balance dysfunction in hereditary and spontaneous spastic paraparesis.

OBJECTIVE: To determine how postural sway is affected in people with spastic paraparesis (pwSP) and the impact of different impairments. METHODS: In 20 pwSP and 18 matched healthy controls standing postural sway was measured with eyes open and closed. Vibration threshold, isometric ankle and hip muscle strength and ankle stiffness with the participant at rest or preactivating the muscle was measured. RESULTS: Antero-posterior (AP) and medio-lateral (ML) sway was higher in pwSP. Muscle strength was reduced and ankle stiffness increased in pwSP. Increased vibratory threshold was seen in 35% of participants. Higher total ankle stiffness (R2=0.44) was associated with lower AP sway with eyes open whilst hip abductor weakness was associated with increased ML sway with eyes open (R2=0.36) or closed (R2=0.47) or AP sway with the eyes closed (R2=0.48). CONCLUSIONS: The degree of postural sway was related to muscle paresis of the hip abductors particularly in the ML direction and under conditions of reduced sensory input. People with higher total ankle stiffness have less AP sway suggesting that this may help to stabilise the body.

The effects of functional electrical stimulation on walking in hereditary and spontaneous spastic paraparesis.

OBJECTIVES: To investigate in people with spastic paraparesis (SP): 1) the factors contributing to foot drop and reduced toe clearance while walking; 2) short-term effects of bilateral functional electrical stimulation (FES) of the common peroneal nerve. MATERIALS AND METHODS: Long term (>0.5 years) users of FES with SP were compared to matched controls (N = 11 per group). Ankle strength and plantarflexor stiffness and walking kinematics were objectively recorded. The effects of FES on: 1) perceived efficacy; 2) muscle torque and ankle motion; 3) clinical outcome measures and walking kinematics were assessed. Results were compared using an analysis of covariance. RESULTS: Ankle weakness and stiffness is higher among people with SP. Higher plantarflexor stiffness is associated with reduced swing phase dorsiflexion; higher toe clearance while walking is associated with increased hip flexion. FES increases dorsiflexor torque, improves toe clearance and dorsiflexion in swing phase, and significantly improves walking speed (p < 0.05). CONCLUSIONS: There are multiple causes of tripping in people with SP; FES reduces foot drop and improves walking speed.

Muscle paresis and passive stiffness: key determinants in limiting function in Hereditary and Sporadic Spastic Paraparesis.

BACKGROUND: People with Hereditary and Sporadic Spastic Parapresis (SP) walk with a stiff legged gait characterised by a lack of knee flexion. OBJECTIVE: We investigated the relationship between lower limb strength and stiffness and knee flexion during swing phase while walking in 20 people with SP and 18 matched controls. METHODS: Maximal isometric strength was measured using a dynamometer. Passive stiffness and spasticity was assessed during motor-driven slow (5°/s) and fast (60°/s) stretches at the ankle and knee while the subject was relaxed or preactivating the muscle. Walking was assessed using 3D motion analysis. RESULTS: Isometric muscle strength was decreased in people with SP with over a 50% reduction in strength being found in the ankle dorsiflexors. Passive stiffness, assessed during slow stretches, was 35% higher in the plantarflexors in people with SP (P<0.05). Faster stretches induced large stretch evoked muscle activity and over a 110% increase in stiffness at the ankle and knee in people with SP reflecting the presence of spasticity (P<0.05). However, stretch reflex size and stiffness was similar between the groups following identical stretches of the pre-activated muscle (P>0.05). Lower knee flexion during swing phase was associated with reduced knee flexion velocity at the end of stance phase which in turn was associated with reduced plantarflexor strength and increased passive stiffness in the knee extensors. CONCLUSIONS: The relative importance of muscle paresis and passive stiffness in limiting walking in SP suggests that these impairments should be the target of future therapies.

Intrathecal baclofen in multiple sclerosis: too little, too late?

The majority of patients with multiple sclerosis (MS) have symptoms of spasticity that increasingly impair function as the disease progresses. With appropriate treatment, however, quality of life can be improved. Oral antispasticity medications are useful in managing mild spasticity but are frequently ineffective in controlling moderate to severe spasticity, because patients often cannot tolerate the adverse effects of increasing doses. Intrathecal baclofen (ITB) therapy can be an effective alternative to oral medications in patients who have a suboptimal response to oral medications or who cannot tolerate dose escalation or multidrug oral regimens. ITB therapy may be underutilized in the MS population because clinicians (a) are more focused on disease-modifying therapies rather than symptom control, (b) underestimate the impact of spasticity on quality of life, and (c) have concerns about the cost and safety of ITB therapy. Delivery of ITB therapy requires expertly trained staff and proper facilities for pump management. This article summarizes the findings and recommendations of an expert panel on the use of ITB therapy in the MS population and the role of the physician and comprehensive care team in patient selection, screening, and management.

An electronic regulatory document management system for a clinical trial network.

A computerized regulatory document management system has been developed as a module in a comprehensive Clinical Trial Management System (CTMS) designed for an NIH-funded clinical trial network in order to more efficiently manage and track regulatory compliance. Within the network, several institutions and investigators are involved in multiple trials, and each trial has regulatory document requirements. Some of these documents are trial specific while others apply across multiple trials. The latter causes a possible redundancy in document collection and management. To address these and other related challenges, a central regulatory document management system was designed. This manuscript shares the design of the system as well as examples of it use in current studies.