Maria B. D. Resende

Sleep and neuromuscular disorders in children

Children suffering from neuromuscular diseases are at an increased risk of sleep-related breathing disorders (SRBD) such as obstructive sleep apnea syndrome (OSAS) and hypoventilation as well as central sleep apnea, which is frequent in these patients due to diaphragmatic weakness. They are at higher risk for developing complications of nocturnal hypoxemia, including pulmonary hypertension, cor pulmonale and neurocognitive dysfunction. Neuromuscular disorders and OSAS are both prevalent disorders and frequently overlap. Sleep-related hypoventilation/hypoxemia due to neuromuscular diseases may be exacerbated in the presence of OSAS; these children are likely to experience greater severity and duration of sleep-related hypoxemia than are children with either disorder alone. Additionally, some of these children have reduced central neural chemoresponsiveness. The development of SRBD in these patients further impairs their quality of life and worsens their respiratory status. We review the literature on the diagnosis and treatment of SRBD in children with a variety of neuromuscular disorders.

Merosin-deficient congenital muscular dystrophy (CMD) : a study of 25 Brazilian patients using MRI

Background: Merosin-deficient congenital muscular dystrophy (CMD) is characterized clinically by hypotonia and muscular weakness and, on imaging studies, by white matter (WM) abnormality. Objective: To evaluate MRI findings in Brazilian patients with merosin-deficient CMD. Materials and methods: Twenty-five patients were evaluated using MRI. Three patients presented with partial merosin deficiency and 22 with total merosin deficiency. Follow-up examinations were done in 7 cases. T1- and T2-weighted images were performed in all examinations, and fluid-attenuated inversion recovery (FLAIR) was performed in 15. Enhanced images were done in 11 cases. The WM involvement was classified according to location and severity. Results: From 1991 to 2004, 32 MRI examinations were performed. Severe involvement was found in 23 patients in the frontal and temporal lobes, in 18 patients in the parietal lobes, and in 7 patients in the occipital lobes. The brain stem (n=5), cerebellum (n=6), internal capsules (n=1), and external capsules (n=5) were also affected. One patient had occipital pachygyria, and one had cerebellar vermian hypoplasia. No gadolinium enhancement was noted. Follow-up MRI showed no interval change (n=4), progression (n=1), or improvement of the findings (n=2). Conclusion: This series of patients demonstrated that there was no correlation between the extent of WM abnormality on MRI and the clinical status and degree of merosin deficiency (partial or total). Bilateral WM involvement was seen to be more prominent in the parietal, frontal, and temporal regions of the brain. The brain stem and internal and external capsules were less affected. Cerebellar WM involvement is rare. Changes on follow-up imaging studies did not correlate with the clinical status of the patient.

Lung function monitoring in patients with duchenne muscular dystrophy on steroid therapy

BackgroundDuchenne muscular dystrophy (DMD) is a sex-linked inherited muscle disease characterized by a progressive loss in muscle strength and respiratory muscle involvement. After 12 years of age, lung function declines at a rate of 6 % to 10.7 % per year in patients with DMD. Steroid therapy has been proposed to delay the loss of motor function and also the respiratory involvement.MethodIn 21 patients with DMD aged between seven and 16 years, the forced vital capacity (FVC) and the forced expiratory volume in one second (FEV1) were evaluated at three different times during a period of two years.ResultsWe observed in this period of evaluation the maintenance of the FVC and the FEV1 in this group of patients independently of chronological age, age at onset of steroid therapy, and walking capacity.ConclusionThe steroid therapy has the potential to stabilize or delay the loss of lung function in DMD patients even if they are non-ambulant or older than 10 years, and in those in whom the medication was started after 7 years of age.

Motor function measure scale, steroid therapy and patients with Duchenne muscular dystrophy

OBJECTIVE To assess the evolution of motor function in patients with Duchenne muscular dystrophy (DMD) treated with steroids (prednisolone or deflazacort) through the Motor Function Measure (MFM), which evaluates three dimensions of motor performance (D1, D2, D3). METHODS Thirty-three patients with DMD (22 ambulant, 6 non-ambulant and 5 who lost the capacity to walk during the period of the study) were assessed using the MFM scale six times over a period of 18 months. RESULTS All the motor functions remained stable for 14 months in all patients, except D1 for those who lost their walking ability. In ambulant patients, D2 (axial and proximal motor capacities) motor functions improved during six months; an improvement in D3 (distal motor capacity) was noted during the total follow-up. D1 (standing posture and transfers) and total score were useful to predict the loss of the ability to walk. CONCLUSIONS The use of the MFM in DMD patients confirms the benefits of the steroid treatment for slowing the progression of the disease.

Schwartz-Jampel syndrome: report of five cases.

We describe five patients with Schwartz-Jampel syndrome (SJS) examined at the outpatient service for neuromuscular disorders at our Institution from 1996 to 1999 with the objective of emphasizing the characteristic dysmorphic phenotype of SJS and its different clinical forms. Two cases presented SJS-type 1A, two had SJS-type 1B and one manifested SJS-type 2. Two boys with 3 and 13 years of age had generalized stiffness and the characteristic facial as well as osteoarticular changes from birth. Other two boys with 11 and 7 years had less marked dysmorphic changes at birth and manifested myotonia, as a limiting factor, during the second year of age. A girl with two months of age had severe myotonia from birth leading to feeding difficulties. In all cases the diagnosis was based on dysmorphic features, and on electromyographic changes showing continuous electrical activity of muscle fibers. All were treated with carbamazepine, 20-30 mg/Kg since diagnosis. The four boys (all with normal intelligence) improved of myotonia in daily activities, markedly in three, and moderately in one. The girl did not improve and showed global development delay: by the last follow-up (at 20 months of age) she did not sit unsupported, and had mental retardation. Carbamazepine in SJS-type 1 improves general daily performance and psychological status of the patients.

King-Denborough Syndrome: report of two Brazilian cases

We report on two boys aged 2 and 6 years-old respectively with dysmorphic face, ptosis, down-slanting palpebral fissures, hypertelorism, epicanthic folds, low-set ears, malar hypoplasia, micrognathia, high-arched palate, clinodactyly, palmar simian line, pectus excavatum, winging of the scapulae, lumbar lordosis and mild thoracic scoliosis who present congenital hypotonia, slightly delayed motor development, diffuse joint hyperextensibility and mild proximal weakness. The muscle biopsy revealed minimal but identifiable changes represented by size fiber variability, type I fiber predominance and atrophy, perimysial fibrous infiltration and some disarray of the intermyofibrillary network. These cases correspond to the first Brazilian reports of the King-Denborough syndrome and our objective is increasing the awareness of this disorder as these patients are predisposed to developing malignant hyperthermia.

Congenital Muscular Dystrophy With Dropped Head Linked to the LMNA Gene in a Brazilian Cohort

BACKGROUND Congenital muscular dystrophy is a clinically and genetically heterogeneous group of myopathies. Congenital muscular dystrophy related to lamin A/C is rare and characterized by early-onset hypotonia with axial muscle weakness typically presenting with a loss in motor acquisitions within the first year of life and a dropped-head phenotype. METHODS Here we report the clinical and histological characteristics of four unrelated Brazilian patients with dropped-head syndrome and mutations in the LMNA gene. RESULTS All patients had previously described mutations (p.E358K, p.R249W, and p.N39S) and showed pronounced cervical muscle weakness, elevation of serum creatine kinase, dystrophic pattern on muscle biopsy, and respiratory insufficiency requiring ventilatory support. Three of the patients manifested cardiac arrhythmias, and one demonstrated a neuropathic pattern on nerve conduction study. CONCLUSION Although lamin A/C--related congenital muscular dystrophy is a clinically distinct and recognizable phenotype, genotype/phenotype correlation, ability to anticipate onset of respiratory and cardiac involvement, and need for nutritional support remain difficult.