Deborah Gaebler-Spira

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.

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.

Drooling, saliva production, and swallowing in cerebral palsy

Fourteen participants (six females, eight males) ranging in age from 7 years 11 months to 18 years 2 months (mean 11y 7mo) with a confirmed diagnosis of spastic cerebral palsy (CP) were included in the study. Participants included those who drooled (CP+, n=14); age- and sex-matched children with spastic CP who were dry to mild and never to infrequent droolers (CP-, n=14) as well as typically developing peers (CTRL, n=14) served as controls. Frequency of swallowing was measured by using simultaneous cervical ausculation and videotaping of the head and neck. Saliva production was measured with the Saxon test, a simple gauze-chewing procedure. In addition, Pediatric Evaluation of Disability Inventory (PEDI), Test of Nonverbal Intelligence-3 (TONI-3), dysarthria severity scale, and Gross Motor Function Classification System (GMFCS) scores were obtained for each participant. Both groups of participants with CP tended to swallow less frequently than typically developing participants and tended to produce less saliva than typically developing controls; however, these differences were not statistically significant. No correlation was found between amount of saliva produced and amount drooled (r=0.245). An analysis of variance (ANOVA) conducted on the PEDI functional skills mean scores indicated significant differences between the three groups (F(2,39)=23.522,p<0.0001). Likewise, an ANOVA conducted on the TONI-3 scores revealed statistically significant differences between the three groups (F(2,39)=31.761, p<0.0001). A Spearmans rho correlation indicated that GMFCS scores were not significantly correlated with drooling severity (Spearmans rho correlation=0.3951,p=0.037). Drooling severity was found to be positively correlated with dysarthria severity (Spearmans rho correlation=0.82,p<0.0001). These findings suggest that drooling in patients with CP is related to swallowing difficulties rather than hypersalivation.

Prospective open-label clinical trial of trihexyphenidyl in children with secondary dystonia due to cerebral palsy

Although trihexyphenidyl is used clinically to treat both primary and secondary dystonia in children, limited evidence exists to support its effectiveness, particularly in dystonia secondary to disorders such as cerebral palsy. A prospective, open-label, multicenter pilot trial of high-dose trihexyphenidyl was conducted in 23 children aged 4 to 15 years with cerebral palsy judged to have secondary dystonia impairing function in the dominant upper extremity. All children were given trihexyphenidyl at increasing doses over a 9-week period up to a maximum of 0.75 mg/kg/d. Trihexyphenidyl was subsequently tapered off over the next 5 weeks. Objective motor assessments were performed at baseline, 9 weeks, and 15 weeks. The primary outcome measure was the Melbourne Assessment of Unilateral Upper Limb Function, tested in the dominant arm. Tolerability and safety were monitored closely throughout the trial. Of the 31 children who agreed to participate in the study, 5 failed to meet entry criteria and 3 withdrew due to nonserious adverse events (chorea, drug rash, and hyperactivity). Three children required a dosage reduction because of nonserious adverse events but continued to participate. The 23 children who completed the study showed a significant improvement in arm function at 15 weeks (P = .045) but not at 9 weeks (P = .985). Post hoc analysis showed that a subgroup (n = 10) with hyperkinetic dystonia (excess involuntary movements) worsened at 9 weeks (P = .04) but subsequently returned to baseline following taper of the medicine. The authors conclude that scientific evidence for the clinical use of trihexyphenidyl in cerebral palsy remains equivocal. Trihexyphenidyl may be a safe and effective for treatment for arm dystonia in some children with cerebral palsy if given sufficient time to respond to the medication. Post hoc analyses based on the type of movement disorder suggested that children with hyperkinetic forms of dystonia may worsen. A larger, randomized prospective trial stratified by the presence or absence of hyperkinetic movements is needed to confirm these results.

Use of botulinum toxin type A in pediatric patients with cerebral palsy: a three-center retrospective chart review.

Over the last several years, botulinum toxin type A has gained widespread use for the management of focal spasticity in children with cerebral palsy. To assess the current patterns of botulinum toxin type A use in the clinical setting, the dose, muscles injected, age at injection, and interval between injections of botulinum toxin type A treatments were examined in a retrospective chart review of children with cerebral palsy (N = 270) over a 2-year period at three major treatment centers. The average dose of botulinum toxin type A across the three centers ranged from 7.7 to 10.8 U/kg body weight, and the average total amount of botulinum toxin type A injected at a single visit ranged from 154 to 205 U. The majority of botulinum toxin type A injections were to the muscles to the lower limbs. The average age at first injection was 6.2 years, and the average interval between injections ranged from 134 to 199 days. (J Child Neurol 2001;16:113-118).

Oral bisphosphonates to treat disuse osteopenia in children with disabilities: a case series.

Children with congenital conditions who are nonambulatory have been observed to have pathologic fractures due to disuse osteopenia. Data support the use of intravenous bisphosphonates to treat this in children with disabilities, but there are no data to guide the use of oral bisphosphonate medication. Ten nonambulatory children with disuse osteopenia secondary to either static brain injury or spina bifida were started on alendronate. Investigators completed a chart review of each subject. There were 17 fractures before starting alendronate and 1 fracture in the follow-up period. All children with nociceptive behavior or pain complaints (5/10) had their symptoms resolve after treatment. Despite the presence of gastrointestinal comorbidities (7/10 with a history of gastroesophageal reflux disease, 5/10 taking reflux medication, and 4/10 with PEG tubes), only 1 of the 10 children discontinued the medication secondary to gastrointestinal complaints. This case series offers evidence that disabled nonambulatory children tolerate alendronate, and it may decrease fractures in those at risk from severe disuse osteopenia.

Functional Improvement After Pediatric Spinal Cord Injury

Garcia RA, Gaebler-Spira D, Sisung C, Heinemann AW: Functional improvement after pediatric spinal cord injury. Am J Phys Med Rehabil 2002;81:458–463. Objective To describe the functional gain (FGain) with pediatric spinal cord injury inpatient rehabilitation and to identify the relationship of various factors to FGain in pediatric spinal cord injury inpatient rehabilitation. Design Retrospective chart review of a series of 91 children with spinal cord injury admitted from 1993 to 1998 in a freestanding rehabilitation hospital. Admission and discharge functional status were assessed with the Pediatric Functional Independence Measure (WeeFIM™) instrument for children ≤7 yr and the Adult Functional Independence Measure (FIM™) instrument for children >7 yr. The outcome measure is the FGain (difference between the discharge and admission functional status). Results Significant gains in functional status were observed in all patients. FGain was not significantly related to age, sex, length of inpatient rehabilitation, pathogenesis, or completeness or neurologic level of injury. However, there was a trend for higher FGain for patients with incomplete spinal cord injury and traumatic spinal cord injury. Conclusions Functional improvement occurs with pediatric spinal cord injury inpatient rehabilitation. There is a trend for higher FGain in patients with less severe injury and traumatic injury. The lack of relationship between FGain and length of inpatient rehabilitation suggests that a variety of other factors influence the relationship between FGain and length of inpatient rehabilitation.

Injury prevention for children with disabilities.

Little injury data exists for children who have disabilities. There is an urgent need to address injury prevention and to improve safety standards for this group. Understanding the epidemiology of injuries will allow clinicians to accurately advise patients and their families on individual risks and counsel them in steps to take to reduce those risks. Safety information must be tailored to consider each childs functional impairments. All children who have disabilities are at risk for maltreatment. Open discussion of this problem is warranted given the immensity of the problem. Identifying parental concerns and supporting parents in the use of respite resources are appropriate. For children who have problems in mobility, falls are the number one concern. Collaboration with reliable vendors and therapists that adhere to standards for safe seating is essential for reducing the risk of wheelchair tips and falls. In addition, therapists should be directed to provide mobility training for activities from safe transfers to street crossing in a community setting. Parents should be counseled to approach their childs injury risk based on the childs cognitive and behavioral level rather than their chronological level. Knowledge of the childs developmental quotient or intelligence quotient will also allow the clinician to accurately formulate an injury prevention plan. Many children will always need supervision for tasks that put them in situations of injury risk (i.e., swimming, street crossing, bathing). Sensorineural deficits such as blindness or deafness create significant alterations in negotiating the environment and an increased risk of injury. Awareness of the special needs for fire risk reduction and street safety are critical in this population. The collection of injury data is critical to define the scope of the problem and to influence changes in policy and the development of technical standards. Educational efforts focused on safety should include pediatricians, rehabilitative therapists, social workers, teachers, parents, and--most importantly--the empowerment of children as they age injury-free into adults. SUGGESTED STRATEGIES: A national injury surveillance system for children who have disabilities should be developed to identify injury risk factors for children with disabilities. Children with disabilities should be monitored as a separate risk group in data collection regarding injuries. Parents should be aware of the cognitive level of their child and its influence on their injury risk. Crash testing on passenger restraints should include crash dummies whose physical characteristics resemble those of children who have disabilities. Families should have an emergency evacuation plan with specific consideration of their disabled child in the event of an emergency. Risk of burns to insensate skin and risks of thermal and friction trauma should be discussed when appropriate. The fire department and the police department should be notified of the presence of a child who has a disability in the home. Parents must be aware of the risk of falls to children who are mobile but cognitively impaired and to those in wheelchairs regardless of cognitive ability. Hospitals must have Child Protective Services teams with specific training in abuse to children with disabilities. Discussion of maltreatment risk should be addressed during routine office visits and appropriate resources should be made available to provide support to families. Educational programs should be developed to alert providers to the risks of abuse of children who have disabilities.

Selective Posterior Rhizotomy and Soft-tissue Procedures for the Treatment of Cerebral Diplegia

The results of selective posterior rhizotomy in fifty patients (group I) and of soft-tissue procedures in fifty patients (group II), all 100 of whom had cerebral diplegia and were seen in a private office, were reviewed retrospectively. No effort was made to randomize the treatment, as the selection criteria for the two procedures are different. We evaluated the range of motion and the ability and quality of walking preoperatively and postoperatively as well as the need for additional operative intervention in the two groups. The average age of the patients in both groups was five years (range, three to twelve years in group I and one to thirteen years in group II). The average duration of follow-up in both groups was four years (range, one to six years in group I and one to seven years in group II). Thirty-two patients (64 percent) in group I and forty-one patients (82 percent) in group II were able to walk independently at the latest follow-up examination. Both groups had an over-all improvement in the ranges of abduction of the hips and dorsiflexion of the ankles, a decrease in the flexion contractures of the hips, and more normal popliteal angles; however, with the numbers available, there were no significant differences in these measurements between the two groups at the 0.05 percent confidence level. Despite the overall improvement in range of motion, thirty-one patients in the rhizotomy group subsequently had soft-tissue releases, and twenty-two patients in the soft-tissue-release group had additional operative intervention.

Deep vein thrombosis in the disabled pediatric population

The incidence of deep vein thrombosis (DVT) in the disabled pediatric population has rarely been studied. The purpose of our retrospective study was to define the incidence in patients younger than 18 years of age who were in a rehabilitation center. We reviewed the charts of 532 children admitted to the center from 1983 through 1987, and found a 2.2% overall incidence of DVT. The largest group of children under 18 of age with documented or suspected DVT was the group with spinal cord injuries (SCI). There were 87 SCI children, 67 of whom were between the ages of 15 and 18. Of the 67, 7 (10%) had DVT: 1 of the 20 SCI children under age 15 had DVT. There were single cases of DVT documented in children with: meningoencephalitis, arteriovenous malformation, closed head injuries, and Guillian-Barré syndrome. We studied the risk involved in treating DVT with heparin and formulated recommendations based on our findings.