Enterostomy tube placement in children with spinal muscular atrophy type 1.

OBJECTIVE: To determine the major complication rate in the first 30 days after enterostomy tube insertion in infants with spinal muscular atrophy (SMA) type 1. STUDY DESIGN: A retrospective case review of all children with SMA type 1 who had a gastrostomy or gastrojejunostomy tube placed by the image-guided technique at the Hospital for Sick Children from 1994-2004. Major complications were classified as peritonitis, aspiration pneumonia, respiratory failure, nonelective admission to the pediatric intensive care unit, and death. RESULTS: Twelve children were identified as having SMA type 1 with an enterostomy tube insertion. The median age at tube insertion was 6.1 months (range 2.2 to 15.8 months). Major complications in the first 30 days after the procedure included aspiration pneumonia (5/12 patients [41.6%]), respiratory failure requiring admission to the pediatric intensive care unit (4/12 [33%]), and death (2/12 [16.7%]). Children with development of aspiration pneumonia were significantly older at time of tube insertion (P < .05) than those with no aspiration. CONCLUSIONS: Major complications including death are seen in children with SMA type 1 in the first 30 days after enterostomy tube insertion.

Nemaline rods and complex I deficiency in three infants with hypotonia, motor delay and failure to thrive.

Three infants are described who had nemaline rods on muscle biopsy and isolated deficiency of complex I of the respiratory chain on biochemical analysis. They all manifested failure to thrive from birth, and hypotonia and muscle weakness within the first three months of life. Different genetic defects leading to isolated complex I deficiency have been described associated with a variety of morphological changes on muscle biopsy, but rods have not been described. Nemaline rods have been secondary phenomena in a number of conditions, as well as being the primary abnormality in nemaline myopathy. However, the combination of nemaline rods and complex I deficiency is an association not previously reported.

Deflazacort in Duchenne muscular dystrophy: a comparison of two different protocols.

We compare the long-term benefits and side effects of deflazacort using two treatment protocols from Naples (N) and Toronto (T). Boys with Duchenne muscular dystrophy between the ages of 8 and 15 years and who had four or more years of deflazacort treatment were reviewed. Diagnostic criteria included males with proximal muscle weakness evident before 5 years, increased serum creatine kinase and genetic testing and/or a muscle biopsy consistent with Duchenne muscular dystrophy. Thirty-seven boys were treated with protocol-N using deflazacort at a dose of 0.6 mg/kg per day for the first 20 days of the month and no deflazacort for the remainder of the month. Boys with osteoporosis received daily vitamin D and calcium. Deflazacort treatment started between 4 and 8 years of age. Thirty-two were treated with protocol-T using deflazacort at a dose of 0.9 mg/kg per day, plus daily vitamin D and calcium. Treatment started between 6 and 8 years of age. All boys were monitored every 4-6 months. The results were compared with age-matched controls in the two groups (19 for protocol-N and 30 for protocol-T). For the boys treated with protocol-N, 97% were ambulatory at 9 years (control, 22%), 35% at 12 years (control, 0%), 25% at 15 years (control, 0%). For the 32 boys treated with protocol-T, 100% were ambulatory at 9 years (control, 48%), 83% at 12 years (control, 0%) and 77% at 15 years (control, 0%). No aids or leg braces were used for ambulation. In boys 13 years and older, a scoliosis of >20 degrees developed in 30% of the boys on protocol-N, 16% on protocol-T and 90% of controls. For protocol-N, no cataracts were observed while in protocol-T, 30% of boys had asymptomatic cataracts that required no treatment. Fractures occurred in 19% (control 16%) of boys on protocol-N and 16% (control, 20%) of boys on protocol-T. This report illustrates: (a) the importance of collaborative studies in developing treatment protocols in Duchenne muscular dystrophy and (b) the long-term beneficial effects of deflazacort treatment in both protocols. However, the protocol-T seems to be more effective and frequently is associated with asymptomatic cataracts.

Creatine monohydrate enhances strength and body composition in Duchenne muscular dystrophy.

OBJECTIVE: To determine whether creatine monohydrate (CrM) supplementation increases strength and fat-free mass (FFM) in boys with Duchenne muscular dystrophy (DD). METHODS: Thirty boys with DD (50% were taking corticosteroids) completed a double-blind, randomized, cross-over trial with 4 months of CrM (about 0.10 g/kg/day), 6-week wash-out, and 4 months of placebo. Measurements were completed of pulmonary function, compound manual muscle and handgrip strength, functional tasks, activity of daily living, body composition, serum creatine kinase and gamma-glutamyl transferase activity and creatinine, urinary markers of myofibrillar protein breakdown (3-methylhistidine), DNA oxidative stress (8-hydroxy-2-deoxyguanosine [8-OH-2-dG]), and bone degradation (N-telopeptides). RESULTS: During the CrM treatment phase, there was an increase in handgrip strength in the dominant hand and FFM (p < 0.05), with a trend toward a loss of global muscle strength (p = 0.056) only for the placebo phase, with no improvements in functional tasks or activities of daily living. Corticosteroid use, but not CrM treatment, was associated with a lower 8-OH-2-dG/creatinine (p < 0.05), and CrM treatment was associated with a reduction in N-telopeptides (p < 0.05). CONCLUSIONS: Four months of CrM supplementation led to increases in FFM and handgrip strength in the dominant hand and a reduction in a marker of bone breakdown and was well tolerated in children with DD.

Muscle weakness in critically ill children.

OBJECTIVE: To establish the incidence of muscle weakness in critically ill children. METHODS: Neuromuscular examinations were performed in 830 children without identified antecedent or acute neuromuscular disease (age 3 months to 17 years 11 months) admitted for >24 hours to a pediatric intensive care unit (ICU) over a 1-year period. RESULTS: Fourteen of 830 (1.7%) patients had generalized weakness. Four failed repeated attempts to extubate. Multiple organ dysfunction occurred in 11 patients and sepsis in 9. Most children received corticosteroids, neuromuscular blocking agents, or aminoglycoside antibiotics. Eight of the 14 children were solid organ or bone marrow transplant recipients. Muscle biopsy showed evidence of acute quadriplegic myopathy in all three patients in whom biopsy was performed. Three patients died. In survivors, significant weakness persisted for 3 to 12 months following ICU discharge. CONCLUSIONS: Muscle weakness is an infrequent but significant feature of critical illness in children. Transplant recipients seem to be at particular risk.

Video-assisted thoracoscopic thymectomy in juvenile myasthenia gravis.

As video-assisted thoracoscopic surgery for thymectomy has been reported to be as effective as traditional open surgical approaches in predominantly adult patients with myasthenia gravis, we applied this procedure to juvenile patients with this condition. Six patients underwent total thymectomy using the video-assisted technique (1997-98). Six patients in whom a median transsternal approach was used (1989-95) formed the comparison group. The two patient groups were similar in terms of age at thymectomy and preoperative clinical severity. There were no serious perioperative complications in either group. Minimum post-thymectomy duration of follow-up in the video-assisted thoracoscopic surgery patients was 2.3 years (mean 2.7 years), with all patients clinically improved over their baseline status. Preliminary results suggest that video-assisted thymectomies are comparably effective to transsternal procedures in treating generalized juvenile myasthenia gravis and can be safely performed in children as young as 20 months of age. In addition, video-assisted surgeries are less invasive than transsternal approaches, significantly shorten the postoperative hospital stay, and have superior cosmetic results.

Thoracoscopic thymectomy in juvenile myasthenia gravis.

BACKGROUND: Although transsternal thymectomy is an effective method in the treatment of juvenile myasthenia gravis (JMG) it is traumatic in pediatric patients. Thoracoscopic thymectomy offers an effective and less traumatic approach with respect to cosmesis and postoperative recovery. METHODS: A retrospective analysis of 6 consecutive patients treated with thoracoscopic thymectomy was performed. Perioperative parameters and cost analysis were compared with those of 6 consecutive open procedures performed before the study. RESULTS: Thoracoscopic thymectomy can be performed in patients as young as 1.6 years. There was no conversion to open procedure and no perioperative morbidity and mortality. The length of operating time and the surgical cost of thoracoscopic procedure were not significantly different from those of open procedure. The length of hospitalization, however, was significantly shorter with thoracoscopic procedure, and hence the overall cost was significantly reduced (P < .05). An intermediate follow-up shows that outcome after thoracoscopic procedure is equally as effective as open procedure. CONCLUSIONS: Thoracoscopic thymectomy offers an equally effective but cosmetically more acceptable approach than sternotomy. It has a quicker recovery period and appears to be a less costly alternative to transsternal thymectomy.

Basal lamina abnormality in the skeletal muscle of Walker-Warburg syndrome.

The basal lamina of skeletal muscle fibers has been reported to be thinned and disrupted in patients with Fukuyama and laminin-alpha-2-deficient congenital muscular dystrophies. The basal lamina is normal in other, later-onset, muscular dystrophies, but the plasma membrane is disrupted. It is unknown whether the dystrophic process in Walker-Warburg syndrome (WWS) is characterized by a basal laminal abnormality, a sarcolemmal abnormality, or both. The present study examined the skeletal muscle of a 3-month-old patient with WWS by immunohistochemistry and electron microscopy and compared the findings with control muscle samples. In control samples the basal lamina of skeletal muscle fibers was a continuous, uniformly dense structure associated with sarcolemma. In WWS the basal lamina appeared deranged, with disruptions in nonnecrotic muscle fibers. Furthermore, in some fibers the basal lamina was thinner, and in others, it was duplicated. Dystrophin, laminin-alpha-2, and adhalin stains revealed normal immunoreactivity. The disruptions in the basal lamina may play a primary role in the degeneration of muscle fibers in WWS. When compared with the dystrophies with a primary sarcolemmal defect, it appears that those with primary basal lamina abnormalities (WWS, laminin-alpha-2-deficient, and Fukuyama congenital muscular dystrophies) present early in life, and the phenotype is more severe.

The natural history and ophthalmic involvement in childhood myasthenia gravis at the hospital for sick children.

OBJECTIVE: To characterize signs, symptoms, and the natural history of myasthenic syndromes in pediatric patients. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Thirty-four patients with a diagnosis of myasthenia were identified from either the hospital's or treating physician's database. METHODS: Retrospective chart review, clinical examination, and telephone interview. MAIN OUTCOME MEASURES: Information pertaining to the ophthalmologic and neurologic examination, diagnostic interventions, and treatment was noted. Patients with active disease, attending during the study period, were examined at their outpatient visits. Those who no longer attended the hospital were contacted by means of a telephone interview to complete their follow-up. RESULTS: Thirty-four children were found to have myasthenia. Two had transient neonatal myasthenia, which resolved quickly. Seven (20.6%) patients had congenital myasthenic syndromes (CMS) and 25 (73.5%, 19 females) were affected with autoimmune myasthenia gravis (AMG). In those patients with severe CMS, three showed signs of generalized weakness, including failure to thrive, frequent apneas, and aspirations. In four patients with mild CMS, eye signs were relatively more prominent. In all patients with CMS, strabismus, ophthalmoplegia, and ptosis were the main ophthalmologic signs and remained relatively constant. Fourteen (56%) patients with AMG had ocular signs and symptoms, and five of them progressed to systemic involvement in 7.8 months on average (range, 1-23). The remaining nine patients with ocular AMG had either strabismus or ptosis and were treated with pyridostigmine (nine patients) and prednisone (two patients). Patients with ocular AMG were seen at 78 months on average, those with systemic AMG at 85.6 months. Systemic AMG was seen in 16 patients. No thymomas were found in 14 patients who underwent thymectomy. Of the 25 patients with AMG, 8 are still being treated, 8 are in remission for an average of 65.2 months and are asymptomatic, 4 patients are receiving long-term immunosuppressants (1 has likely sustained permanent damage to her extraocular muscles with complete ophthalmoplegia and ptosis), and 4 have been lost to follow-up. Finally, one patient died after aspiration because of bulbar weakness. CONCLUSIONS: Patients with CMS varied in the degree of severity. Apneic attacks, aspiration, and failure to thrive may obscure the diagnosis. Compared with AMG, their ophthalmologic signs and symptoms were usually permanent. Visual signs and symptoms were usually prominent in those patients with active AMG, but those in remission were asymptomatic. More than half of the patients with juvenile AMG had ocular symptoms. Generalization occurred in a minority in an average of 7.8 months. Patients entered remission after approximately 2 years of treatment and were visually asymptomatic. This study suggests that long-term permanent damage to the extraocular muscles as a result of juvenile AMG is rare. Myasthenia gravis is a life-threatening disease as evidenced by the death of one of our patients. Many of these patients are first seen by the ophthalmologist who can aid the diagnosis, screen for amblyopia, and monitor the patient's response to therapy.

MRI of the cauda equina in CIDP: clinical correlations.

Isolated reports have documented enhancement and/or enlargement of spinal nerve roots on magnetic resonance imaging (MRI) in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). This work examines those findings in a consecutive series of 16 patients with CIDP, with blinded comparison to MRI in 13 disease controls, including five patients with Charcot-Marie-Tooth disease type 1A. MRI sequences consisted of T1 weighted sagittal and axial views, before and after administration of gadolinium. Blinded MRI interpretation was performed independently by two neuroradiologists. MRI results were correlated with data collected from chart review. Enhancement of the cauda equina was seen in 11 of 16 CIDP patients (69%), and in none of 13 control subjects. Nerve roots were enlarged, most significantly in the extraforaminal region, in three CIDP patients, and in one patient with Charcot-Marie-Tooth type 1A. MRI findings did not correlate with disease activity and severity, nor with any clinical or laboratory features in patients with CIDP.

IGIV in neurology--evidence and recommendations.

OBJECTIVE: To summarize the evidence for neurologic uses of immunoglobulin, intravenous (IGIV) in light of present-day clinical usage. This summary guided the development of practice recommendations for the effective and efficient use of IGIV in Neurology. METHODS: MEDLINE was searched to identify pertinent English-language review articles and original reports (n = 231) on the use of IGIV in neurology (excluding editorials, letters, and comments) published before March 1998. Evidence on alternative therapies was only included as compared to IGIV. The relevant original reports and review articles and older classic studies (n = 92) were synthesized into an information foundation. Extracted data included laboratory and clinical findings, objective measures, and clinical impressions. Clinical recommendations were based on evidence quality, graded by study design, clinical experiences of IGIV in Neurology Advisory Board members, and the conditions of IGIV use in therapy. RESULTS AND CONCLUSIONS: In neurology, many disorders are poorly understood, and the mechanisms behind beneficial regimens even less so. As a result, it is fairly common for best-practice decisions to rest on weaker evidence. The usefulness of IGIV in neurology can be described by a "combined score" based on evidence quality and strength of impact. Combined scores ranged from A+ (strongly recommended) to C (recommended as a last resort). The following clinical recommendations are made: IGIV is: strongly recommended for the treatment of Guillain-Barré syndrome (A+); favorably recommended for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy, dermatomyositis, and multifocal motor neuropathy (A); recommended as a second resort for the treatment of multiple sclerosis and myasthenia gravis (B); and recommended as a last resort for the treatment of polymyositis, inclusion-body myositis, intractable epilepsies, and stiff-man syndrome (C).

Myasthenia gravis and polymyositis as manifestations of chronic graft-versus-host-disease.

Myasthenia gravis and polymyositis are each a rare manifestation of immune dysregulation in chronic graft-versus-host disease (cGVHD). We report a 4-year-old boy with idiopathic acquired aplastic anemia who developed myasthenia gravis 22 months and polymyositis 69 months after an allogeneic BMT (5/6 matched, MLC-nonreactive). The occurrence of both syndromes in one patient is unique. Autoimmune dysfunction may be associated with the development of cGVHD as demonstrated by the high incidence of prior aplastic anemia in BMT patients presenting with myasthenia gravis and polymyositis. Recognition of these neurologic manifestations is important in the diagnosis and treatment of cGVHD.

Cardiac manifestations of congenital fiber-type disproportion myopathy.

Cardiac involvement has not been a reported feature of congenital fiber-type disproportion myopathy. We describe two children, aged 13 years and 1 year, respectively, who presented with serious cardiac symptomatology in conjunction with congenital fiber-type disproportion. One child developed dilated cardiomyopathy and medically intractable congestive heart failure necessitating cardiac transplantation at the age of 13 years. The second (unrelated) child developed atrial fibrillation with rapid atrioventricular conduction requiring treatment with digoxin. Skeletal muscle biopsy findings in both children showed congenital fiber-type disproportion with no evidence of a structural, dystrophic, or metabolic myopathy. Adenosine triphosphatase (ATPase) reacted sections showed type I hypotrophy with a predominance of type I fibers, confirmed by histogram analysis. Examination of the heart from patient 1 at the time of transplantation confirmed dilated cardiomyopathy with hypertrophic myocardiocytes. Although cardiomyopathy is commonly associated with other childhood myopathies, to our knowledge it has not been a feature in reported cases of congenital fiber-type disproportion. We recommend close cardiac assessment, with annual electrocardiograms, of children with congenital fiber-type disproportion.

Long-chain L-3-hydroxyacyl-coenzyme A dehydrogenase deficiency neuropathy: response to cod liver oil.

Docosahexaenoic acid (DHA) deficiency has recently been documented in several children with long-chain L-3-hydroxyacyl-coenzyme A dehydrogenase deficiency (LCHADD). We studied a 13-year-old boy with LCHADD who had limb girdle myopathy, recurrent myoglobinuria, and progressive sensorimotor axonopathy with demyelination. At 11 years of age, he was started on cod liver oil extract, high in DHA content. Over 12 months, he demonstrated a marked clinical recovery. Nerve conduction studies (NCS) demonstrated reappearance of previously absent posterior tibial and peroneal nerve responses and the amplitudes on motor ulnar and median NCS markedly increased from 7- to 14-fold, respectively.

Severe classical congenital muscular dystrophy and merosin expression.

It has been suggested that patients with autosomal recessive merosin deficient congenital muscular dystrophy (CMD), as opposed to the merosin positive cases form a homogeneous subgroup of a clinically more severe form of CMD. We examined merosin expression in muscle biopsies from five children with the severe classical form of CMD. Merosin deficiency was found only in 1 patient, a 6-year-old female, with abnormal brain myelination. However, her initial biopsy did not reveal the classical picture of dystrophy. The four merosin positive cases exhibited severe muscle weakness but their brain imagings were normal. There were no familial cases, except for the mother of 1 patient who had a milder form of the disease, suggesting an autosomal dominant mode of inheritance. In contrast to previous reports, the merosin deficient CMD cases were rare in our group. Furthermore, merosin positive cases were also associated with severe phenotype suggesting that a severe phenotype is not exclusive to merosin deficient cases. Finally, the absence of merosin in a neonate with hypotonia and weakness can be helpful in making a definitive diagnosis of CMD, even though the dystrophic process may not be evident yet and histology may be non-specific.

Congenital cytoplasmic body myopathy with survival motor neuron gene deletion or Werdnig-Hoffmann disease.

A 5-week-old boy became rigid and developed cardiac arrest after receiving succinylcholine. He was resuscitated and ventilated but died at 5 months. Muscle biopsy demonstrated no neurogenic features and numerous cytoplasmic bodies, suggesting the possibility of congenital myopathy with cytoplasmic bodies. However, molecular analysis revealed a homozygous deletion of exons 7 and 8 of the survival motor neuron (SMN) gene, suggesting that the patient had Werdnig-Hoffmann disease. We recommend that every patient with congenital cytoplasmic body myopathy be tested for SMN gene deletion.

Amplitudes of sural and radial sensory nerve action potentials in orthodromic and antidromic studies in children.

Several previous studies of adults have reported that the amplitudes of the sural and superficial radial nerve action potentials (SN and SRN SNAP respectively) are larger with antidromic than with orthodromic recordings. However, this difference has not been documented in children. This study evaluated the amplitudes of SN and SRN SNAPs obtained with antidromic and orthodromic recordings in children with and without neuropathy and compared these data with findings in adults. The SN or SRN or both of 10 neurologically normal children, 6 children with neuropathy and 7 healthy adults were studied with surface stimulation and recording. The position of the stimulating and recording electrodes for the orthodromic recordings was the reverse of that for the antidromic recordings. Peak-to-peak SNAP amplitudes were measured and analyzed. The mean of the SRN SNAP amplitude was significantly higher with the antidromic than the orthodromic technique for the first and third groups (p < 0.05). The mean SN SNAP amplitude was higher in the three groups, but not statistically significant when the data for the children and adult normal groups were combined and reanalyzed (p < 0.05). Consistent responses were obtained with both techniques. However, the antidromic technique was superior to the orthodromic technique because of the greater amplitude of responses. We recommend the use of the antidromic technique because of its greater amplitudes, ease of use and potential reduction of discomfort to the patient.

Intravenous immunoglobulin treatment in children with Guillain-Barré syndrome.

We have retrospectively reviewed the data of 75 consecutive children diagnosed with Guillain-Barré syndrome (GBS) and hospitalized in two centres. There were 51 children with GBS treated in Ankara, Turkey and 24 patients treated in Toronto, Canada. To evaluate the effect of intravenous immunoglobulin (IVIG) treatment, the patients were divided into three groups. All 24 Canadian patients received IVIG in a dose of 1 g/kg/day for 2 days. In the Ankara group 23 children received 0.4 g/kg/day for 5 days and the remaining 28 patients in that group received supportive treatment only. In all but two patients IVIG was started within the first 2 weeks of neuropathic symptoms. The patients' data, including mean functional grades, frequency of bulbar signs and autonomic dysfunction and age were similar in all three groups. Analysis of the short-term outcome demonstrated that the patients treated with IVIG had a significantly faster rate of recovery. Mean time-lapse until improvement of one functional grade was 17.4 days in the IVIG group from Toronto, and 20.8 days in the IVIG group and 62.4 days in the non-IVIG group of patients from Ankara. We conclude that IVIG has considerable efficacy in the treatment of children with GBS. Furthermore, we have also demonstrated a faster rate of recovery in patients who received a total dose of IVIG in 2 days as opposed to 5 days.