Acute flaccid myelitis in childhood: a retrospective cohort study.

BACKGROUND AND PURPOSE: Clusters of acute limb weakness in paediatric patients have been linked to outbreaks of non-polio enteroviruses, termed acute flaccid myelitis (AFM). Outside these clusters, in countries where polio is not endemic, this poliomyelitic-like illness is rare in childhood and its natural history is not well defined. We describe presenting features, investigation findings and long-term outcome of a series of children with AFM. METHODS: This was a retrospective cohort study. RESULTS: Eight children (six females) aged 3 months to 8 years (median age 5 years) met case criteria. Initial symptoms were pain (n = 7) followed by limb weakness with hypotonia (n = 8). Flaccid paralysis occurred in only three patients. Two had cranial nerve dysfunction. Magnetic resonance imaging of the spinal cord demonstrated grey matter involvement particularly affecting the anterior cord, with longitudinally extensive changes in three children. Cerebrospinal fluid examination showed pleocytosis in six children with raised cerebrospinal fluid protein in five. Nerve conduction and electromyography findings were consistent with a motor neuronopathy. Residual deficits were common, with moderate to severe weakness seen in five patients. Median follow-up was 28 months (range 17-108 months, 30.4 patient years in total). CONCLUSIONS: Acute flaccid myelitis is an uncommon condition in childhood with a high rate of significant long-term morbidity. AFM should be considered in children presenting with acute limb pain and weakness.

Two novel germline KRAS mutations: expanding the molecular and clinical phenotype.

Noonan and Cardio-facio-cutaneous (CFC) syndromes are characterized by typical dysmorphic features, cardiac defects, short stature, variable ectodermal anomalies, and intellectual disability. Both belong to the Ras/mitogen-activated protein kinase pathway group of disorders and clinical features overlap other related conditions, notably LEOPARD and Costello syndromes. KRAS mutations account for about 2% of reported Noonan and <5% of reported CFC cases. The mutation spectrum includes recurrent missense changes clustering in particular domains of the KRAS protein and conferring gain-of-function. We report three patients from two unrelated families with novel missense KRAS mutations, p.K147E and p.Y71H. Both mutations affect a residue which is highly conserved in KRAS and other RAS isoforms. One of the families includes a mother and son pair who represent the first report of a vertically transmitted KRAS mutation. In addition, the mother and son pair had peripheral neuropathy, complicated by Charcot arthropathy in the mother. An unusual phenotypic effect of the specific KRAS mutation or a coincidence of two independent disorders may be considered. KRAS mutation-associated phenotypes appear to be subject to considerable clinical heterogeneity. All three cases highlight the challenges of clinical assessment in KRAS mutation-positive patients, and the utility of molecular testing as an adjunct to diagnosis.

Development of clinical practice guidelines for allied health and nursing assessment and management of Duchenne muscular dystrophy.

PURPOSE: To provide evidence-based guidance specific to allied health and nursing practice for the assessment and management of individuals with Duchenne muscular dystrophy (DMD). MATERIALS AND METHODS: Thirteen key focus areas were identified in consultation with health professionals and consumer advocacy groups. A series of systematic literature reviews were conducted to identify assessment and management strategies for each key focus area. A consensus process using modified Delphi methodology, including an Australia-New Zealand expert consensus meeting, was conducted. Recommendations underwent consultative review with key groups before being finalised and prepared for dissemination. RESULTS: This clinical practice guideline (CPG) generated 19 evidence-based recommendations, 117 consensus-based recommendations and five research recommendations across the 13 focus areas to inform allied health assessment and management of individuals with DMD. CONCLUSIONS: The resulting recommendations can be used in conjunction with existing medical CPGs to improve, standardise and advocate for allied health and rehabilitation care in DMD. The process used here may be useful for the development of CPGs in other rare diseases.Implications for rehabilitationImplementation-ready evidence-based statements to guide clinical care of individuals with DMD are provided with the potential to improve participation, function in the community and quality of life.A model for developing best practice statements for other rare neurological diseases is described.Allied health and nursing health professionals should focus research efforts to generate quality evidence to support rehabilitation practice.

Is Reluctance to Share Alzheimer's Disease Biomarker Status with a Study Partner a Barrier to Preclinical Trial Recruitment?

BACKGROUND: Preclinical Alzheimer's disease clinical trials test candidate treatments in individuals with biomarker evidence but no cognitive impairment. Participants are required to co-enroll with a knowledgeable study partner, to whom biomarker information is disclosed. OBJECTIVE: We investigated whether reluctance to share biomarker results is associated with viewing the study partner requirement as a barrier to preclinical trial enrollment. DESIGN: We developed a nine-item assessment on views toward the study partner requirement and performed in-person interviews based on a hypothetical clinical trial requiring biomarker testing and disclosure. SETTING: We conducted interviews on campus at the University of California, Irvine. PARTICIPANTS: Two hundred cognitively unimpaired older adults recruited from the University of California, Irvine Consent-to-Contact Registry participated in the study. MEASUREMENTS: We used logistic regression models, adjusting for potential confounders, to examine potential associations with viewing the study partner requirement as a barrier to preclinical trial enrollment. RESULTS: Eighteen percent of participants reported strong agreement that the study partner requirement was a barrier to enrollment. Ten participants (5%) agreed at any level that they would be reluctant to share their biomarker result with a study partner. The estimated odds of viewing the study partner requirement as a barrier to enrollment were 26 times higher for these participants (OR=26.3, 95% CI 4.0, 172.3), compared to those who strongly disagreed that they would be reluctant to share their biomarker result. Overall, participants more frequently agreed with positive statements than negative statements about the study partner requirement, including 76% indicating they would want their study partner with them when they learned biomarker results. CONCLUSIONS: This is one of the first studies to explore how potential preclinical Alzheimer's disease trial participants feel about sharing their personal biomarker information with a study partner. Most participants viewed the study partner as an asset to trial enrollment, including having a partner present during biomarker disclosure.

Reliability and validity of the FSHD-composite outcome measure in childhood facioscapulohumeral dystrophy.

This study aims to investigate intra-rater reliability and construct validity of the Facioscapulohumeral Dystrophy Composite Outcome Measure (FSHD-COM), in childhood FSHD. Participants included eighteen children with FSHD, and matched healthy controls. Reliability data were collected from 15 participants with FSHD over two testing sessions. Validity data were collected from all participants. Participants with FSHD completed; the FSHD-COM (and modified pediatric version), Motor Function Measure-32 (MFM-32), FSHD Severity Scales, Performance of the Upper Limb 2.0, Pediatric Quality of Life™ Neuromuscular Module and pediatric FSHD Health-Index Questionnaire. Both versions of the FSHD-COM showed excellent intra-rater reliability (ICC1,2 > 0.99, lower 95%CI > 0.98) with a Minimal Detectable Change (MDC95%) of ≤14.5%. The FSHD-COM had robust and widespread correlations with other related outcome measures. The FSHD-COM versions and 6 min walk test effectively discriminated between children with and without FSHD; the MFM-32 and 10 m walk/run test did not. Ceiling effects were not observed on either version of the FSHD-COM. Reliability and validity findings in this childhood FSHD study concord with estimates in adults. Both versions of the FSHD-COM were effective in discriminating disease in children with mild FSHD symptoms. The FSHD-COM has the potential to be a useful measure of function across the life span.

Measurement properties and utility of performance-based outcome measures of physical functioning in individuals with facioscapulohumeral dystrophy - A systematic review and evidence synthesis.

Access to reliable, valid, accurate and responsive outcome measures is essential to ensure standards of care and clinical trial readiness in facioscapulohumeral dystrophy. Review aims: 1. identify and provide a descriptive summary of all outcome measures used to measure physical function. 2. systematically appraise the evidence on measurement properties (reliability, construct validity, measurement error and responsiveness) of performance-based outcome measures of physical function in individuals diagnosed with facioscapulohumeral dystrophy. Selected electronic health-related databases were searched from inception - Feb 2019. Two authors independently screened studies for eligibility and extracted data for psychometric evidence. The methodological quality of outcome measure studies was appraised using the consensus-based standards for the selection of health measurement instruments (COSMIN) checklist. Of 12 identified outcome measures, four required high-technology equipment. Only three were FSHD specific. The FSH-clinical score had 'moderate' quality positive evidence for reliability. The remaining measures had 'low' to 'very low' quality evidence supporting properties of reliability, validity, responsiveness and measurement error. Identified studies tended towards low recruitment in middle-aged, ambulant individuals making results hard to generalise across lifespan and levels of severity. There is a paucity of measurement evidence supporting the use of outcome measures in people with facioscapulohumeral dystrophy.

Autosomal dominant congenital spinal muscular atrophy--a possible developmental deficiency of motor neurones?

We describe a kindred with an unusual congenital lower motor neuron disorder with significant but static muscle weakness predominantly affecting the lower limbs. The proband had talipes equinovarus and congenital hip contractures and did not walk until 19 months of age. Lower-extremity predominant, primarily proximal weakness was identified on assessment at three years. Over a 20 year follow-up there has been no clinical progression. The proband has a four-year-old daughter with very similar clinical findings. Electromyography and muscle biopsy suggest reduced numbers of giant normal duration motor units with little evidence of denervation or reinnervation. Dominant congenital spinal muscular atrophy predominantly affecting the lower limbs is rarely described. It is possible that the disorder is due to a congenital deficiency of motor neurons.

Interventions for the prevention and treatment of pes cavus.

BACKGROUND: People with pes cavus frequently suffer foot pain, which can lead to significant disability. Despite anecdotal reports, rigorous scientific investigation of this condition and how best to manage it is lacking. OBJECTIVES: To assess the effects of interventions for the prevention and treatment of pes cavus. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group Trials Register (April 2007), MEDLINE (January 1966 to April 2007), EMBASE (January 1980 to April 2007), CINAHL (January 1982 to April 2007), AMED (January 1985 to April 2007), all EBM Reviews (January 1991 to April 2007), SPORTdiscuss (January 1830 to April 2007) and reference lists of articles. We also contacted known experts in the field to identify additional published or unpublished data. SELECTION CRITERIA: We included all randomised and quasi-randomised controlled trials of interventions for the treatment of pes cavus. We also included trials aimed at preventing or correcting the cavus foot deformity. DATA COLLECTION AND ANALYSIS: Two authors independently selected papers, assessed trial quality and extracted data. MAIN RESULTS: Only one trial (custom-made foot orthoses) fully met the inclusion criteria. Two additional cross-over trials (off-the-shelf foot orthoses and footwear) were also included. Both studies assessed secondary biomechanical outcomes less than three-months after randomisation. Data used in the three studies could not be pooled due to heterogeneity of diagnostic groups and outcome measures. The one trial that fully met the inclusion criteria investigated the treatment of cavus foot pain in 154 adults over a three month period. The trial showed a significant reduction in the level of foot pain, measured using the validated 100-point Foot Health Status Questionnaire, with custom-made foot orthoses versus sham orthoses (WMD 10.90; 95% CI 3.21 to 18.59). Furthermore, a significant improvement in foot function measured with the same questionnaire was reported with custom-made foot orthoses (WMD 11.00; 95% CI 3.35 to 18.65). There was also an increase in physical functioning of the Medical Outcomes Short Form - 36 (WMD 9.50; 95% CI 4.07 to 14.93). There was no difference in reported adverse events following the allocation of custom-made (9%) or sham foot orthoses (15%) (RR 0.61; 95% CI 0.26 to 1.48). AUTHORS' CONCLUSIONS: In one randomised controlled trial, custom-made foot orthoses were significantly more beneficial than sham orthoses for treating chronic musculoskeletal foot pain associated with pes cavus in a variety of clinical populations. There is no evidence for any other type of intervention for the treatment or prevention of foot pain in people with a cavus foot type.

Childhood chronic inflammatory demyelinating polyneuropathy: clinical course and long-term outcome.

We reviewed the clinical history, electrophysiologic and pathologic findings, and response to therapy of 16 children with chronic inflammatory demyelinating polyneuropathy. The majority presented with lower limb weakness. Sensory loss was uncommon. The illness was monophasic in seven children, relapsing in six, and three had a slowly progressive course. All patients were treated with immunosuppressive agents. In 11, the initial treatment was prednisolone. All had at least a short-term response but five went on to develop a relapsing course. Intravenous immunoglobulin was the initial treatment in four patients. Three responded rapidly, with treatment being stopped after a maximum of 5 months. In resistant chronic inflammatory demyelinating neuropathy, in addition to prednisolone and immunoglobulin, plasma exchange, azathioprine, cyclosporine, methotrexate, cyclophosphamide and pulse methylprednisolone were tried at different times in different patients. On serial neurophysiologic testing slowing of nerve conduction persisted for long periods after clinical recovery. Follow-up was for an average of 10 years. When last seen 14 patients were asymptomatic, two having mild residual deficits. Childhood chronic inflammatory demyelinating neuropathy responds to conventional treatment and generally has a favourable long-term outcome.

Changing outcome over 13 years of very low birthweight infants.

The survival prospects for infants of birthweight less than or equal to 1500 g born in recent years have improved. Evidence for a corresponding decrease in long-term morbidity of survivors is conflicting but recent reports from some centers indicate that high morbidity rates are occurring. Until additional satisfactory reports are available on the outcome of very low birthweight (VLBW) infants born after 1975, preferably from a community or region, uncertainty will continue. The outcome of three cohorts of VLBW infants, born in the Royal Women's Hospital, Melbourne between 1966 and 1978 is reported; more than 90% of each cohort were fully assessed, aged 2-8 years. There were 169 long-term survivors from the first cohort (1966-1970 births) and 72 from the second cohort (1973-74 births); survival rates were 37.1% and 37.3% respectively; however, for the 1977-78 births, there were 161 survivors, a significant increase to 68.3%. In the first cohort, 32.7% had one or more visual defects and 3.9% were blind but visual morbidity decreased progressively in cohorts 2 and 3; 3% of the second cohort and 1.2% of the third cohort were blind. There was a trend for a decrease in severe sensorineural deafness. Cerebral palsy increased progressively, respectively 2.6%, 4.5% and 11.9% in the first, second and third cohorts. There was a significant increase in the mean Mental Developmental Index of the Bayley Scales at the age of 2 years from 75.38 for the 64 children born in 1966-70 compared with 90.96 for 150 children in the 1977-78 cohort. Although there had been an increase in upper social class families in the more recent cohort, improvement in test scores was still highly significant when higher social classes (1-3 Congalton Scale) were excluded. However, there was no significant improvement in the 6 year psychological test scores of the first and second cohorts. There was a steady increase in occurrence of cerebral palsy. Significance associations in the 1977-78 cohort were found with only 2 perinatal variables (use of theophylline and necrotizing entercolitis). Furthermore, 17 (89.5%) of children had a five-minute Apgar score greater than 5 and 14 (73.7%) did not require ventilatory support: Prevention of cerebral palsy by selective treatment in the delivery room or nursery was not feasible for prediction of this condition was not possible from perinatal risk factors.

Cerebral vasculitis in a case of Sydenham's chorea.

A 10-year-old girl with acute-onset hemichorea had multiple areas of abnormal signal seen on magnetic resonance imaging of the brain, associated with middle and anterior cerebral artery vasculitis seen on cerebral angiography. Her serology and clinical course were supportive of the diagnosis of Sydenham's chorea. Other causes of cerebral vasculitis were excluded. Follow-up studies revealed resolution of changes seen on magnetic resonance imaging and partial resolution of angiographic abnormalities. This is the first report of abnormal cerebral angiography in Sydenham's chorea.

Influenza A encephalitis with movement disorder.

Influenza A is an uncommon but well-recognized cause of viral encephalitis in childhood, occurring most commonly during community influenza outbreaks. The authors report four cases of influenza A encephalitis that occurred during an Australian epidemic in 1997-1998. Choreoathetosis during the acute phase of infection or basal ganglia involvement on neuroimaging was observed in three of the four patients. These findings in pediatric encephalitis are suggestive of influenza A infection and may guide investigation and early diagnosis.

Anterior horn cell disease and olivopontocerebellar hypoplasia.

To date, fewer than 30 cases of anterior horn cell disease with associated olivopontocerebellar hypoplasia have been reported. We describe five patients and review the literature on this uncommon disorder. In addition to a syndrome of progressive spinal muscular atrophy similar to that seen in Werdnig-Hoffmann disease, this disorder is characterised by hypoplasia of the olivary nuclei, pons, and cerebellum. Additional clinical features may include dysmorphism, abnormal eye movements, stridor, congenital joint contractures, and enlarged kidneys. Pontocerebellar hypoplasia may be associated with posterior fossa cystic malformations, cerebral atrophy, and a demyelinating neuropathy.

Relationship of growth and psychoneurologic status of 2-year-old children of birthweight 500-999 g.

There were 257 liveborn infants of birthweight 500-999 g born in one tertiary centre in the 5 1/4 years commencing January 1977; 86 (33.5%) survived to 2 years of age, corrected for prematurity and 83/86 (96.5%) were fully assessed. The prevalence of cerebral palsy was 10/83 (12%) and 17/83 (20%) had a major impairment. The distribution of weights and heights for 2-year-old boys and girls was significantly lower than for the standard population, as was the head circumference distribution for boys; the distribution of the Mental Developmental Index (Bayley Scales) was not related to the head circumference or body weight at two years or to head-circumference/bodyweight or height ratios. At birth measurements of weight, length and head circumference were under the 3rd percentile for 13/86 (15%), 9/86 (10.5%) and 9/86 (10.5%) respectively. By 2 years of age, weight, length and head circumference were under the 3rd percentile in 23/83 (27.7%), 26/83 (31.3%) and 4/83 (4.8%) respectively. 12 children who were SGA at birth were fully assessed at 2 years; the group of 6, who continued with poor postnatal weight gains (under the 3rd percentile) had the highest rate of major impairment but included were the only extremely SGA twins and the only two major malformations in the study. We found no association of other health problems or unfavourable social factors with poor postnatal growth or impaired outcome.

EMG profiles of lower extremity muscles during cycling at constant workload and cadence.

Limited conclusions concerning the variability in EMG patterns during cycling can be made from available data in the literature because of methodological differences which include electrode placement and experimental design. The purpose of this study was to monitor EMG signals from ten lower extremity muscles over a large number of pedalling cycles in experienced cyclists at constant workload and cadence. Variability across subjects was evaluated by calculating the coefficient of variation (CV) at 10% intervals of the pedalling cycle. Within subject EMG patterns were very consistent within a single trial. The single-joint hip and knee extensors (gluteus maximus, vastus medialis, and vastus lateralis) had the lowest CV values (less than 30%). This low variability appears to support their role as power generators. Variability was generally higher in the hamstring muscles with two biceps femoris patterns emerging despite relatively similar experimental conditions. EMG signals from surface and fine wire electrodes for the hamstring muscles were compared for possible contribution to the discrepancies in the EMG profiles. Fine wire EMG data were quite similar to those obtained using surface electrodes, indicating that crosstalk had minimal effect, in general, on the hamstring signals. The tibialis anterior, gastrocnemius, and soleus muscles displayed fairly repeatable patterns, with variability highest in the first 20% of the pedalling cycle for all muscles studied.

Observations of body mass index in Duchenne muscular dystrophy: a longitudinal study.

BACKGROUND/OBJECTIVES: Nutritional issues that are associated with Duchenne muscular dystrophy (DMD) remain poorly understood. The aim of this analysis was to describe and explore longitudinal observations of body mass index (BMI) in a cohort of children with DMD. SUBJECTS/METHODS: Anthropometric and clinical characteristics were collected retrospectively and longitudinally for boys with DMD seen in two large neuromuscular clinics. BMI Z-scores were determined using the Centers for Disease Control and Prevention reference values for children (2000). RESULTS: Medical records (n=193) were examined from which 75% were included for analysis. The mean age of the cohort at the time of data collection was 11.9 years, with 72% of patients currently or previously using steroids. The highest prevalence of obesity based on the BMI Z-score was 50% at the age of 10 years. Longitudinally, BMI Z-scores from the age of 2 to 12 years plot approximately one s.d. above the mean, after which there is a marked and progressive decline. BMI gainers were identified for whom BMI Z-score increased by 1.65 units compared with the 0.09 units in non-gainers. BMI gainers were younger when they had their first BMI measurement (5.9 vs 7.2 years), and this measure was significantly lower compared with the non-gainers (BMI Z-score: 0.04 vs 1.17). In this cohort, BMI was associated with age, ambulatory status and lung function. CONCLUSIONS: This study demonstrates that boys with DMD using steroid therapy experience shifts in BMI. A declining BMI appears to be associated with increasing age. Interpretation of growth patterns is limited here by a lack of normative growth references in DMD.

Binaural speech processing in individuals with auditory neuropathy.

Auditory neuropathy disrupts the neural representation of sound and may therefore impair processes contingent upon inter-aural integration. The aims of this study were to investigate binaural auditory processing in individuals with axonal (Friedreich ataxia) and demyelinating (Charcot-Marie-Tooth disease type 1A) auditory neuropathy and to evaluate the relationship between the degree of auditory deficit and overall clinical severity in patients with neuropathic disorders. Twenty-three subjects with genetically confirmed Friedreich ataxia and 12 subjects with Charcot-Marie-Tooth disease type 1A underwent psychophysical evaluation of basic auditory processing (intensity discrimination/temporal resolution) and binaural speech perception assessment using the Listening in Spatialized Noise test. Age, gender and hearing-level-matched controls were also tested. Speech perception in noise for individuals with auditory neuropathy was abnormal for each listening condition, but was particularly affected in circumstances where binaural processing might have improved perception through spatial segregation. Ability to use spatial cues was correlated with temporal resolution suggesting that the binaural-processing deficit was the result of disordered representation of timing cues in the left and right auditory nerves. Spatial processing was also related to overall disease severity (as measured by the Friedreich Ataxia Rating Scale and Charcot-Marie-Tooth Neuropathy Score) suggesting that the degree of neural dysfunction in the auditory system accurately reflects generalized neuropathic changes. Measures of binaural speech processing show promise for application in the neurology clinic. In individuals with auditory neuropathy due to both axonal and demyelinating mechanisms the assessment provides a measure of functional hearing ability, a biomarker capable of tracking the natural history of progressive disease and a potential means of evaluating the effectiveness of interventions.

Pediatric sciatic neuropathies: a 30-year prospective study.

OBJECTIVE: The incidence, cause, and prognosis of sciatic neuropathy in children is not well understood. We report our 30-year experience of 53 patients with pediatric sciatic neuropathies (SN). METHODS: Prospective review of the history, physical examination, electrophysiologic findings, and clinical course of children with SN. RESULTS: The etiology of SN injury was varied and included trauma (13), iatrogenic causes (13) (8 orthopedic surgeries and 5 miscellaneous surgeries), prolonged extrinsic compression and immobilization (6), tumors (7), vascular (5), idiopathic and progressive (4), infantile and nonprogressive (2), and unknown, presumed postviral (3). Electrophysiologic studies demonstrated abnormalities in motor conduction studies of the peroneal nerve in 44/53 (83%) or tibial nerve in 35/51 (67%). Sensory conduction studies were abnormal in sural nerve in 34 of 43 cases (79%), and superficial peroneal nerves in 15/25 (60%). Needle EMG was abnormal in peroneal innervated muscles in all subjects, in tibial nerve innervated muscles in 43/51 (84%), and in the hamstrings in 18/29 (62%). Prognosis for recovery was variable and depended on the etiology and the severity of the nerve injury. CONCLUSIONS: SN is an uncommon mononeuropathy in children. The causes of SN are varied in children compared to adults. Electrophysiologic studies in children may be limited by poor tolerance but play an important role in establishing the diagnosis.

A retrospective review of X-linked Charcot-Marie-Tooth disease in childhood.

OBJECTIVE: X-linked Charcot-Marie-Tooth disease (CMTX) is infrequently diagnosed in childhood, and its clinical and neurophysiologic features are not well-described. We reviewed clinical, neurophysiologic, and pathologic findings in 17 children with CMTX. METHODS: This was a retrospective review of children with CMTX from 2 tertiary pediatric hospitals. The diagnosis of CMTX was based on an identifiable connexin 32 mutation (CMTX1) or a consistent pedigree and neurophysiologic features in children without a connexin 32 mutation (CMTX-other). RESULTS: Six boys and 2 girls from 8 kindreds had CMTX1, and 8 boys and 1 girl from 5 kindreds had other forms of CMTX (CMTX-other). Fifteen children, including males and carrier females, were symptomatic from infancy or early childhood (younger than 5 years). In addition to the typical Charcot-Marie-Tooth disease clinical phenotype, some patients had delayed motor development, sensorineural hearing loss, tremor, pathologic fractures, or transient CNS disturbances. Eleven children underwent nerve conduction studies. Median nerve motor nerve conduction velocities were in the intermediate to normal range (30-54 m/s) in all children older than 2 years. Axon loss, reflected by low-amplitude compound muscle action potentials, was present in all patients. A pattern of X-linked dominant inheritance, with carrier females showing an abnormal neurologic or neurophysiologic examination, correlated with the presence of a connexin 32 mutation in all but 2 pedigrees. CONCLUSIONS: The clinical phenotype of CMTX is broader than previously reported. Onset in males and carrier females is most often in early childhood. Families with an X-linked dominant inheritance pattern are likely to have CMTX1.

Randomized, blinded trial of weekend vs daily prednisone in Duchenne muscular dystrophy.

OBJECTIVE: To perform a double-blind, randomized study comparing efficacy and safety of daily and weekend prednisone in boys with Duchenne muscular dystrophy (DMD). METHODS: A total of 64 boys with DMD who were between 4 and 10 years of age were randomized at 1 of 12 centers of the Cooperative International Neuromuscular Research Group. Efficacy and safety of 2 prednisone schedules (daily 0.75 mg/kg/day and weekend 10 mg/kg/wk) were evaluated over 12 months. RESULTS: Equivalence was met for weekend and daily dosing of prednisone for the primary outcomes of quantitative muscle testing (QMT) arm score and QMT leg score. Secondary strength scores for QMT elbow flexors also showed equivalence between the 2 treatment groups. Overall side effect profiles of height and weight, bone density, cataract formation, blood pressure, and behavior, analyzed at 12 months, did not differ between weekend and daily dosing of prednisone. CONCLUSIONS: Weekend dosing of prednisone is equally beneficial to the standard daily dosing of prednisone. Analysis of side effect profiles demonstrated overall tolerability of both dosing regimens. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that weekend prednisone dosing is as safe and effective as daily prednisone in preserving muscle strength and preventing body mass index increases in boys with DMD over a 12-month period.