Linkage analysis of candidate loci in autosomal dominant myotonia congenita.

Electrophysiologic studies in patients with autosomal dominant myotonia congenita (ADMC) have implicated defects of both muscle membrane sodium and chloride channels. An adult skeletal muscle sodium channel (ASkM1) gene maps to chromosome 17q23-25, and defects in this gene are almost certainly responsible for at least three variants of hyperkalemic periodic paralysis (HPP)--myotonic HPP, nonmyotonic HPP, and paramyotonia congenita. A gene for a muscle chloride channel has not yet been mapped in humans, but has been identified in the mouse. The gene for the cystic fibrosis transmembrane regulator (CFTR), which has chloride channel properties, is located on chromosome 7q31. This region is syntenic with the area of mouse chromosome 6 that contains the muscle chloride channel gene, a defect in which is responsible for the ADR phenotype, a murine model of myotonia. We performed linkage analysis using chromosome 17q polymorphisms at D17S74, SCN4A, and GH1, two chromosome 7q31 restriction fragment length polymorphisms, and a dinucleotide repeat polymorphism within the CFTR gene (CFTR-DNR), in three pedigrees with ADMC. The lod scores obtained show that the locus for ADMC is not at ASkM1 and is excluded from a region of at least 24 cM on either side of the CFTR gene.

Recognition memory of item, associative and serial-order information after temporal lobectomy for seizure disorder.

Children, adolescents, and young adults with temporal lobectomy judged the context of their encounters with a word (by deciding about its prior occurrence or familiarity) and also identified word attributes involving associative content and serial order (by indicating word meanings and reconstructing word sequences). Laterality of temporal lobectomy was important for identifying familiarity: individuals with right-sided temporal lobectomies made better judgements than those with left resections about the prior occurrence of target words, with the more successful performance depending on enhanced sensitivity to the familiarity or non-familiarity of what was heard. Identifying the attributes of an item, as contrasted with its prior occurrence, depended on aspects of temporal lobe disorder in conjunction with laterality: deficits of brain structure involving histopathology and significant tissue loss disrupted content memory; compromised brain function resulting from certain post-infantile seizures impaired memory for serial order. In the young brain after temporal lobectomy, there exists a functional dissociation between judging the familiarity of an event and identifying its attributes, a dissociation that depends, not only on laterality of surgery, but also on the structural and functional intactness of the residual brain.

Poliomyelitis-like paralysis during recovery from acute bronchial asthma: possible etiology and risk factors.

A poliomyelitis-like paralytic disease during recovery from an attack of bronchial asthma is described in two young children. They presented at the age of 13 and 22 months, respectively, with acute flaccid paralysis of one or both lower limbs and preserved sensation. Cerebrospinal fluid examinations revealed mild protein elevation in both and pleocytosis in the second infant. Enteroviruses were isolated in a nasal swab and stools of the second patient. Acute onset of flaccid paralysis with absent motor action potential and normal sensory responses, detected by electrophysiologic studies, are highly suggestive of motor anterior horn cell disease in these infants. A multifactorial setup of immune suppression, stress, and neurotoxic drugs during an acute bronchial asthma attack triggered by a viral disease may render the patient vulnerable to viral invasion of the anterior horn cell with enteroviruses other than poliovirus. The overall experience of 22 patients with this serious complication is reviewed.

Thymectomy in juvenile myasthenia gravis.

The long-term results of thymectomy in 24 children with generalized myasthenia gravis are reviewed. Sixteen had complete remission and another seven were improved. This compares favorably with reported spontaneous remission rates of 30%. Because of the low morbidity in recent reports and the possibility that early thymectomy is more beneficial, we recommend thymectomy at the onset of juvenile generalized myasthenia gravis.

Magnetic resonance imaging evaluation of delayed myelination in Down syndrome: a case report and review of the literature.

Magnetic resonance imaging has been found to be useful in assessing brain myelination and provides information on brain maturation. The normal pattern of brain myelination conforms to a fixed sequence, with good pathologic and MRI correlation. Neuropathologic analysis of myelination has shown delayed central myelination in Down syndrome. Delayed myelination on MRI in Down syndrome has not previously been reported. We report a case of Down syndrome with a significant delay in myelination as demonstrated on MRI. This 18-month-old infant had brain myelination equivalent to that expected for an 11-month-old infant. To determine the relative incidence, extent of delayed myelination, and time for recovery to full myelination in Down syndrome, more cases require examination and assessment. Magnetic resonance imaging has the advantage of serial assessment of myelination during brain maturation.

Infant-onset progressive myoclonus epilepsy.

We report the clinical, electroencephalographic, neurophysiologic, and neuroimaging findings in eight children with infant-onset progressive myoclonus epilepsy, all of whom had muscle biopsies performed as as part of the diagnostic evaluation. Each child had myoclonic seizures, generalized tonic-clonic seizures, and neurologic regression or marked developmental delay. Four children died before 3 years of age. Electroencephalograms in seven children showed an abnormally slow background with bilateral multifocal paroxysmal discharges but no burst suppression pattern or photoparoxysmal response. Muscle biopsy specimens were submitted for histopathology and respiratory-chain enzyme studies. Nonspecific abnormalities on light microscopy or electron microscopy were found in seven samples, including increased subsarcolemmal deposits of mitochondria or morphologic mitochondrial changes, but no ragged-red fibers were seen. Respiratory-chain enzyme studies were performed on five samples and in three children (all of whom had a history of elevated lactate in serum or cerebrospinal fluid), there were low levels of rotenone-sensitive reduced nicotinamide adenine dinucleotide (NADH) cytochrome c reductase characteristic of a defect in the complex I part of the respiratory-chain pathway. This study has shown that infant-onset progressive myoclonus epilepsy can be distinguished from other myoclonic epilepsy syndromes of infancy by clinical and electrographic features. Furthermore, respiratory-chain enzyme defects are a relatively common cause of infant-onset progressive myoclonus epilepsy. The absence of ragged-red fibers on muscle histopathology does not preclude a mitochondrial enzyme abnormality.

Clinical progression of giant-axonal neuropathy over a twelve year period.

Giant-axonal neuropathy (GAN), a chronic peripheral neuropathy with associated Central Nervous System dysfunction and tight curly hair, is described in a 17-year-old girl. Biopsies of this girl's muscle and nerve are characteristic of this condition. Her clinical course over a 12 year period characterizes a disease of a slowly progressive nature.

Fatal nemaline myopathy in infancy.

The clinical and neuropathological findings in two infants with congenital nemaline myopathy are described. One patient presented at birth with severe hypotonia, respiratory failure and contractures and died shortly after the neonatal period. The other presented at age two months with hypotonia and, following a period of clinical stability, died at age seven months from respiratory failure. Pathological findings in the fatal neonatal case revealed numerous rod bodies in lingual, pharyngeal, diaphragm and limb muscles, correlating with clinical findings. Significant, but less rod body involvement was found in the diaphragm and limb muscles of the second patient. Although a neural basis has been suggested for this disorder, no abnormalities were found in the central nervous system or in the peripheral nerves of these two severely affected patients.

Somatosensory evoked potentials and nerve conduction studies in patients with Guillain-Barré syndrome.

Somatosensory evoked potentials, F-waves, and nerve conduction studies (NCS) were performed to determine their usefulness in detecting electrophysiologic abnormalities in 23 children in the acute stage of Guillain-Barré syndrome. The studies were performed on average 8.3 days after the onset of neurological symptoms, before the period of maximal weakness. All patients had at least one abnormal test. Somatosensory evoked potentials (SEP) showed most abnormalities: 91% abnormal recordings with posterior tibial nerve (PTN) stimulation and 68% with median nerve (MN) stimulation. The nerve conduction velocities were abnormal in 76% and 67% with PTN and MN stimulation, respectively. The F-waves were abnormal in 66% (PTN) and 56% (MN). The SEP studies were helpful in detecting proximal and central conduction abnormalities in 26% of patients, and they were more sensitive in detecting an abnormality when compared with F-wave recordings. Furthermore, in one patient with normal NCS and F-waves the prolonged lumbar potential-P35 conduction time of the PTN-SEP was the only abnormality found. SEP can detect an abnormality and thus support the clinical diagnosis of Guillain-Barré syndrome in the acute stage when the results of more conventional tests are inconclusive.

Clinical and neurophysiologic response of myopathy and neuropathy in long-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency to oral prednisone.

The purpose of this study was to evaluate the clinical and neurophysiologic responses to oral prednisone therapy in a boy with enzymatically confirmed long-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency in biopsied muscle and cultured skin fibroblasts. This boy presented with progressive limb girdle myopathy, recurrent myoglobinuria, peripheral sensorimotor axonopathy, and intraventricular conduction delays. Prior to prednisone therapy, at age 8 years, he exhibited marked distal weakness greater than proximal weakness with a waddling and high-steppage gait, Gowers' maneuver (10 s to rise from the floor), fatigue after 3-20 yards of walking and the ability to climb only 2 stairs. Serum levels of creatine kinase rose from 34 to 4,124 U/L following mild exertion. Nerve conduction studies revealed progressive axonopathy with secondary demyelination. Four weeks after initiation of oral prednisone (0.75 mg/kg/day) therapy, there was approximately a 100% increase in power and endurance. He was able to walk at least 100 yards before tiring, could rise from sitting on the floor in 3-4 s, and was able to climb 20 steps in 30 s. There was concurrent improvement in nerve conduction studies. Prednisone was gradually withdrawn over the next 4 months to 0.19 mg/kg/day; lower doses of 0.08 mg/kg/day resulted in a marked deterioration in power to the prior state. Although 0.19 mg/kg/day did not maintain the peak power achieved at 0.75 mg/kg/day, it provided adequate baseline power and endurance. It is concluded that there was a significant clinical and neurophysiologic response to prednisone at a dosage > or = 0.16 mg/kg/day. Prednisone may stabilize muscle and neuronal plasma membranes, as well as the fatty acid oxidation enzyme complex in the mitochondrial membrane.

Immune globulins are effective in severe pediatric Guillain-Barré syndrome.

The effect of high-dose intravenous immune globulins was evaluated in an open prospective multicenter study of 26 children with severe Guillain-Barré syndrome. They presented with mild to moderate flaccid weakness of extremities, with cranial nerve involvement (20) and sensory impairment (22). All children rapidly deteriorated in 2-16 days (mean 6) to become bedridden, and 2 children also developed respiratory failure requiring artificial ventilation (Disability Grading Scale 4-5). Immune globulins were then administered at a total dose of 2 gm/kg, on 2 consecutive days, without adverse effects requiring discontinuation of therapy. Marked and rapid improvement was noted in 25 children, who improved by 1 to 2 Disability Grade Scales < or = 2 weeks after the infusion. Twenty were able to walk independently by 1 week, and 1 could be weaned off a ventilator. Eighteen children recovered by 2 weeks. The rest recuperated in a period of four months, including a child who was artificially ventilated for 4 weeks. The uniform rapid improvement and recovery associated with immune globulins contrasts with the slow recovery course in severe natural cases. We conclude that immune globulins are effective and safe in severe childhood-onset Guillain-Barré syndrome and therefore may serve as the initial treatment of choice.

Neonatal Guillain-Barré syndrome.

A term female infant had the clinical manifestations and accompanying electrophysiologic studies to fulfill the criteria of Guillain-Barré syndrome. At birth, she presented with generalized hypotonia, paucity of lower limb movements, and diminished muscle stretch reflexes. At 3 weeks of age, motor nerve conduction studies demonstrated evidence of demyelination and axonal involvement. Progressive clinical improvement was observed beginning at the age of 2 weeks with subsequent normalization of clinical examinations and nerve conduction studies. To our knowledge, this patient is the youngest reported with Guillain-Barré syndrome.

Congenital muscular dystrophy: a clinicopathologic report of 24 cases.

Congenital muscular dystrophy (muscular dystrophy presenting from birth) with a wide spectrum of clinical severity is reported in 24 patients. Progression of symptoms was evident, leading to significant motor handicap in all patients and death in eight cases. Muscle enzyme studies did not always correlate with the severity of the disease. In six cases, initial muscle biopsy showed only minimal, nonspecific abnormalities; however, characteristic dystrophic changes were evident on repeat biopsies. Histochemical and electron microscopic studies did not show consistent changes, except type I predominance in a few cases. Evidently the condition is rarely, if ever, benign and the clinical course cannot be predicted from the initial presentation or early pathologic findings. Clinical, laboratory and pathologic characteristics are outlined for the diagnosis of this disorder.

Nerve conduction in childhood diabetes.

Sixty-nine diabetic children were studied with respect to the motor nerve conduction velocities, duration of illness and adequacy of control.As a group there was a trend for children with diabetes to have slower MNCV than non-diabetic children, and for the slowing to become progressive as the duration of their disease increased. Poorer quality of diabetes control was also associated with progressive slowing of conduction but the exact relationship is uncertain, since no patient who had diabetes for more than four years was well controlled.Theories of causation of peripheral neuropathy in diabetic patients are reviewed; metabolic changes, rather than other factors, are thought most likely in children.