Dennis J. Matthews

Recommendations for the use of botulinum toxin type A in the management of cerebral palsy

Botulinum toxin type A (BTX-A) is increasingly being used for the treatment of childhood spasticity, particularly cerebral palsy. However, until very recently, all such use in this indication has been unapproved with no generally accepted treatment protocols, resulting in considerable uncertainty and variation in its use as a therapeutic agent. In view of the increasing awareness of, and interest in, this approach to the treatment of spasticity, and also the recent licensing in a number of countries of a BTX-A preparation for treating equinus deformity in children, it would seem timely to establish a framework of guidelines for the safe and efficacious use of BTX-A for treating spasticity in children. This paper represents an attempt, by a group of 15 experienced clinicians and scientists from a variety of disciplines, to arrive at a consensus and produce detailed recommendations as to appropriate patient selection and assessment, dosage, injection technique and outcome measurement. The importance of adjunctive physiotherapy, orthoses and casting is also stressed.

Corticosteroid treatment and functional improvement in Duchenne muscular dystrophy: long-term effect.

Balaban B, Matthews DJ, Clayton GH, Carry T: Corticosteroid treatment and functional improvement in Duchenne muscular dystrophy: Long-term effect. Am J Phys Med Rehabil 2005;84:843–850. Objective:To determine and compare the long-term effects of prednisone and deflazacort on the functional status of children with Duchenne muscular dystrophy. Design:A total of 49 boys with Duchenne muscular dystrophy, between the age of 12 and 15 yrs, who were observed over a 7-yr period were reviewed retrospectively. Eighteen had been treated with prednisone, 12 with deflazacort, and 19 had no drug treatment. All boys treated with steroids received medication for >2 yrs before losing their ambulation. Lower and upper limb motor functions, pulmonary function, prevalence of surgery for scoliosis, and side effects were compared. Results:Boys in the steroid groups were significantly more functional and performed better on all tests than boys not treated (P < 0.05). There was no significant difference between the deflazacort- and prednisone-treated groups (P > 0.05). The number of boys having scoliosis surgery in treated groups was significantly less than nontreated boys (P < 0.05). The control group’s pulmonary capacity was decreasing and significantly less than both prednisone- and deflazacort-treated boys. Both deflazacort and prednisone had beneficial effect on pulmonary function and scoliosis. Cataracts, hypertension, behavioral changes, excessive weight gain, and vertebral fracture were noted as serious side effects. Conclusions:Prednisone and deflazacort have a significant beneficial effect on slowing the disease progress. Their usage in Duchenne muscular dystrophy may prolong ambulation and upper limb function with similar potency. Both steroids also improve pulmonary function, in addition to delaying the need for spinal interventions, with similar therapeutic profiles.

Definition and Classification of Negative Motor Signs in Childhood

In this report we describe the outcome of a consensus meeting that occurred at the National Institutes of Health in Bethesda, Maryland, March 12 through 14, 2005. The meeting brought together 39 specialists from multiple clinical and research disciplines including developmental pediatrics, neurology, neurosurgery, orthopedic surgery, physical therapy, occupational therapy, physical medicine and rehabilitation, neurophysiology, muscle physiology, motor control, and biomechanics. The purpose of the meeting was to establish terminology and definitions for 4 aspects of motor disorders that occur in children: weakness, reduced selective motor control, ataxia, and deficits of praxis. The purpose of the definitions is to assist communication between clinicians, select homogeneous groups of children for clinical research trials, facilitate the development of rating scales to assess improvement or deterioration with time, and eventually to better match individual children with specific therapies. “Weakness” is defined as the inability to generate normal voluntary force in a muscle or normal voluntary torque about a joint. “Reduced selective motor control” is defined as the impaired ability to isolate the activation of muscles in a selected pattern in response to demands of a voluntary posture or movement. “Ataxia” is defined as an inability to generate a normal or expected voluntary movement trajectory that cannot be attributed to weakness or involuntary muscle activity about the affected joints. “Apraxia” is defined as an impairment in the ability to accomplish previously learned and performed complex motor actions that is not explained by ataxia, reduced selective motor control, weakness, or involuntary motor activity. “Developmental dyspraxia” is defined as a failure to have ever acquired the ability to perform age-appropriate complex motor actions that is not explained by the presence of inadequate demonstration or practice, ataxia, reduced selective motor control, weakness, or involuntary motor activity.

Reliability of the Tardieu Scale for assessing spasticity in children with cerebral palsy.

OBJECTIVE To measure the Tardieu Scales reliability in children with cerebral palsy (CP) when used by raters with and without experience in using the scale, before and after training. DESIGN Single-center, intrarater and interrater reliability study. SETTING Institutional ambulatory care. PARTICIPANTS Referred children with CP in the pretraining phase (n=5), during training (n=3), and in the posttraining phase (n=15). INTERVENTIONS The Tardieu Scale involves performing passive muscle stretch at 2 velocities, slow and fast. The rater derives 2 parameters; the Spasticity Angle X is the difference between the angles of arrest at slow speed and of catch-and-release or clonus at fast speed; the Spasticity Grade Y is an ordinal variable that grades the intensity (gain) of the muscle reaction to fast stretch. In phase 1, experienced raters without formalized training in the scale graded elbow, knee, and ankle plantar flexors bilaterally, without and with a goniometer. In phase 2, after training, the experienced and nonexperienced raters graded the same muscles unilaterally. MAIN OUTCOME MEASURES Intrarater and interrater reliability of the Tardieu Scale. RESULTS After training, nonexperienced raters had mean +/- SD intrarater and interrater agreement rates across all joints and parameters of 80%+/-14% and 74%+/-16%, respectively. For experienced raters, intrarater and interrater agreement rates before training were 77%+/-13% and 66%+/-15%, respectively, versus 90%+/-8% and 81%+/-13%, respectively, after training (P<.001 for both). Specific angle measurements at the knee were less reliable for the angles of catch measured at fast speed. Across all joints, agreement rates were similar using visual or goniometric measurements. CONCLUSIONS Both parameters of the Tardieu Scale have excellent intrarater and interrater reliability when assessed at the elbow and ankle joints of children with CP, with no difference noted between visual and goniometric measurements. Angle measurements were less reliable at the knee joints. Training was associated with a highly significant improvement in reliability.

Delayed Diagnosis in Duchenne Muscular Dystrophy: Data from the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet)

OBJECTIVE To identify key factors for the delay in diagnosis of Duchenne muscular dystrophy (DMD) without known family history. STUDY DESIGN The cohort comes from the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet), a multistate, multiple-source, population-based surveillance system that identifies and gathers information on all cases of Duchenne and Becker muscular dystrophy born since 1982. We analyzed medical records of 453 Duchenne and Becker muscular dystrophy boys to document the time course and steps taken to reach a definitive diagnosis. RESULTS Among 156 boys without known family history of DMD prior to birth, first signs or symptoms were noted at a mean age of 2.5 years. Concerns resulted in primary care provider evaluation of the child at a mean age of 3.6 years. Mean age at time of initial creatine kinase was 4.7 years. Mean age at definitive diagnosis of DMD was 4.9 years. CONCLUSIONS There is a delay of about 2.5 years between onset of DMD symptoms and the time of definitive diagnosis, unchanged over the previous 2 decades. This delay results in lost opportunities for timely genetic counseling and initiation of corticosteroid treatment. We recommend checking creatine kinase early in the evaluation of boys with unexplained developmental delay.

Prevalence of Duchenne and Becker Muscular Dystrophies in the United States

OBJECTIVE: To estimate prevalence of childhood-onset Duchenne and Becker muscular dystrophies (DBMD) in 6 sites in the United States by race/ethnicity and phenotype (Duchenne muscular dystrophy [DMD] or Becker muscular dystrophy [BMD]). METHODS: In 2002, the Centers for Disease Control and Prevention established the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) to conduct longitudinal, population-based surveillance and research of DBMD in the United States. Six sites conducted active, multiple-source case finding and record abstraction to identify MD STARnet cases born January 1982 to December 2011. We used cross-sectional analyses to estimate prevalence of DBMD per 10 000 boys, ages 5 to 9 years, for 4 quinquennia (1991–1995, 1996–2000, 2001–2005, and 2006–2010) and prevalence per 10 000 male individuals, ages 5 to 24 years, in 2010. Prevalence was also estimated by race/ethnicity and phenotype. RESULTS: Overall, 649 cases resided in an MD STARnet site during ≥1 quinquennia. Prevalence estimates per 10 000 boys, ages 5 to 9 years, were 1.93, 2.05, 2.04, and 1.51, respectively, for 1991–1995, 1996–2000, 2001–2005, and 2006–2010. Prevalence tended to be higher for Hispanic individuals than non-Hispanic white or black individuals, and higher for DMD than BMD. In 2010, prevalence of DBMD was 1.38 per 10 000 male individuals, ages 5 to 24 years. CONCLUSIONS: We present population-based prevalence estimates for DBMD in 6 US sites. Prevalence differed by race/ethnicity, suggesting potential cultural and socioeconomic influences in the diagnosis of DBMD. Prevalence also was higher for DMD than BMD. Continued longitudinal surveillance will permit us to examine racial/ethnic and socioeconomic differences in treatment and outcomes for MD STARnet cases.

Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet): Case Definition in Surveillance for Childhood-Onset Duchenne/Becker Muscular Dystrophy

The Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet) is a multisite collaboration to determine the prevalence of childhood-onset Duchenne/Becker muscular dystrophy and to characterize health care and health outcomes in this population. MD STARnet uses medical record abstraction to identify patients with Duchenne/Becker muscular dystrophy born January 1, 1982 or later who resided in 1 of the participating sites. Critical diagnostic elements of each abstracted record are reviewed independently by >4 clinicians and assigned to 1 of 6 case definition categories (definite, probable, possible, asymptomatic, female, not Duchenne/Becker muscular dystrophy) by consensus. As of November 2009, 815 potential cases were reviewed. Of the cases included in analysis, 674 (82%) were either ‘‘definite’’ or ‘‘probable’’ Duchenne/Becker muscular dystrophy. These data reflect a change in diagnostic testing, as case assignment based on genetic testing increased from 67% in the oldest cohort (born 1982-1987) to 94% in the cohort born 2004 to 2009.

Use of Corticosteroids in a Population-Based Cohort of Boys With Duchenne and Becker Muscular Dystrophy

The use of corticosteroids for treatment of Duchenne and Becker muscular dystrophy in clinical practice from 1991 through 2005 was reviewed in a large population-based cohort (MD STARnet) of boys in 4 regional sites and 6 clinics of the United States. Corticosteroid use increased from 20% (11 of 56 individuals) in 1991 to 44% (93 of 218 individuals) in 2005. Average use varied by site and ranged from 15% to 49%. The median age of corticosteroid initiation was 6.9 years (range, 3.7-17.4 years). Dosage and growth information was available for 102 participants and showed a median dose as 0.729 mg/kg for prednisone and 0.831 mg/kg for deflazacort. T. The most common reasons that corticosteroids were discontinued included weight gain, behavioral side effects, and loss of ambulation, resulting in full-time wheelchair use. Substantial variations in clinical practice were identified among study sites.

Functional Status Scale: New Pediatric Outcome Measure

OBJECTIVE: The goal was to create a functional status outcome measure for large outcome studies that is well defined, quantitative, rapid, reliable, minimally dependent on subjective assessments, and applicable to hospitalized pediatric patients across a wide range of ages and inpatient environments. METHODS: Functional Status Scale (FSS) domains of functioning included mental status, sensory functioning, communication, motor functioning, feeding, and respiratory status, categorized from normal (score = 1) to very severe dysfunction (score = 5). The Adaptive Behavior Assessment System II (ABAS II) established construct validity and calibration within domains. Seven institutions provided PICU patients within 24 hours before or after PICU discharge, high-risk non-PICU patients within 24 hours after admission, and technology-dependent children. Primary care nurses completed the ABAS II. Statistical analyses were performed. RESULTS: A total of 836 children, with a mean FSS score of 10.3 (SD: 4.4), were studied. Eighteen percent had the minimal possible FSS score of 6, 44% had FSS scores of ≥10, 14% had FSS scores of ≥15, and 6% had FSS scores of ≥20. Each FSS domain was associated with mean ABAS II scores (P < .0001). Cells in each domain were collapsed and reweighted, which improved correlations with ABAS II scores (P < .001 for improvements). Discrimination was very good for moderate and severe dysfunction (ABAS II categories) and improved with FSS weighting. Intraclass correlations of original and weighted total FSS scores were 0.95 and 0.94, respectively. CONCLUSIONS: The FSS met our objectives and is well suited for large outcome studies.

PALLIATIVE CARE SERVICES IN FAMILIES OF MALES WITH DUCHENNE MUSCULAR DYSTROPHY

Introduction: Palliative care services that address physical pain and emotional, psychosocial, and spiritual needs may benefit individuals with Duchenne muscular dystrophy (DMD). Methods: The objective of this study was to describe the palliative care services that families of males with DMD report they receive. A questionnaire was administered to families of males with DMD born prior to January 1, 1982. Thirty‐four families responded. Results: Most families (85%) had never heard the term palliative care. Only attendant care and skilled nursing services showed much usage, with 44% and 50% indicating receipt of these services, respectively. Receipt of other services was reported less frequently: pastoral care (27%); respite care (18%); pain management (12%); and hospice care (6%). Only 8 respondents (25%) reported having any type of directive document in place. Conclusion: The data suggest a need for improved awareness of palliative care and related services among families of young men with DMD. Muscle Nerve 44: 93–101, 2011