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The objective of the study was to evaluate the epidemiology of patients with congenital myasthenic syndrome (CMS) in Israel. Targeted mutation analysis was performed based on the clinical symptoms and electrophysiological findings for known CMS. Additional specific tests were performed in patients of Iranian and/or Iraqi Jewish origin. All medical records were reviewed and clinical data, genetic mutations and outcomes were recorded. Forty-five patients with genetic mutations in known CMS genes from 35 families were identified. Mutations in RAPSN were identified in 13 kinships in Israel. The most common mutation was c.-38A>G detected in 8 patients of Iranian and/or Iraqi Jewish origin. Four different recessive mutations in COLQ were identified in 11 kinships, 10 of which were of Muslim-Arab descent. Mutations in CHRNE were identified in 7 kinships. Less commonly detected mutations were in CHRND, CHAT, GFPT1 and DOK7. In conclusion, mutations in RAPSN and COLQ are the most common causes of CMS in our cohort. Specific mutations in COLQ, RAPSN, and CHRNE occur in specific ethnic populations and should be taken into account when the diagnosis of a CMS is suspected.

The objective of the present study was to analyze the diagnostic indications that most often prompt the referral of children and adolescents in the outpatient clinical pediatric practice for electroencephalographic evaluation and to check its utility in these clinical conditions. The electroencephalographic records of 547 consecutive children and adolescents (5-16 years of age) referred to a single community laboratory for the evaluation of various neurologic disorders were prospectively read by a single blinded investigator. Common diagnostic indications included the following: clinical seizures (42%), attention-deficit-hyperactivity disorder (23%), headaches (10.4%), syncope (9.9%), and tic disorder (4.9%). Overall, 76% of records were normal. Slowing of electroencephalographic activity was noted in 1% (attention-deficit-hyperactivity disorder) to 26% (probable epilepsy), and epileptiform activity in 53% of the probable and 29% of the clinically possible epileptics. Epileptiform activity was rarely found in the nonepileptic patients. The results of the present study demonstrate that standard interictal electroencephalogram is being overused during evaluation of various neurologic disorders in children and adolescents, suggesting that its use should be reserved for supporting the diagnosis in those cases in which epilepsy is a reasonable clinical possibility.

A series of 9 infants, ranging in age from 3 months to 5 years (average: 2 years), suffered from idiopathic myopathic carnitine deficiency presenting as hypotonia and motor delay. Secondary carnitine deficiency was eliminated by appropriate tests. Muscle carnitine concentration ranged from 2.3–7.1 nmol/mg non-collagen protein (NCP; average: 4.87 nmol/mg NCP; normal: 22 ± 6 nmol/mg NCP). Lipid accumulation in muscle was observed in 2 of 8 patients. Therapy with l-carnitine (100 mg/kg/day in most patients) was given with clinical and laboratory follow-up 6 months later. In 7 of 9 patients, muscle tone and motor function improved. Muscle carnitine concentration increased to a range of 2.7–23.4 nmol/mg (average: 12.27 nmol/mg). In some patients the muscle carnitine content multiplied by a factor of 3–4, but carnitine concentration reached the normal range in only 2 patients. Most infants with idiopathic carnitine deficiency did benefit from 6 months of therapy; however, in order to achieve full recovery the duration of therapy should probably continue for longer periods, with a dose of not less than 100 mg/kg/day.

Bradykinesia and rigidity developed in a 10-year-old girl during an episode of Sydenham chorea. These parkinsonian features improved over 6 months. Serum analysis demonstrated elevated anti-streptolysin-O and anti-basal ganglia antibodies. We suggest that autoimmune antibodies may cause remitting parkinsonian signs subsequent to streptococcal tonsillitis as part of the spectrum of poststreptococcal CNS disease.

Macrophagic myofasciitis has been almost exclusively detected in adults only. We describe six children of Arab Moslem origin with this disorder. Three presented with hypotonia, developmental delay and seizures and were evaluated for a mitochondrial disorder. The other three children had hypotonia and predominantly motor delay. Five of the six families were consanguineous. A massive collection of macrophages was present in the fascia and adjacent epimysium in all biopsies. The macrophages were periodic-acid-Schiff positive and immunoreactive for CD68. One biopsy which was evaluated by electron microscopy and energy-dispersive X-ray microanalysis showed crystalline structures containing aluminum in macrophages. Two children with motor delay and hypotonia were treated with oral prednisone for 3 months with no clinical improvement. Genetic predisposition probably accounts for the variability in the prevalence of macrophagic myofasciitis in different populations. At least in childhood, there seems to be no connection between macrophagic myofasciitis as a pathological entity and the clinical symptoms and signs.

Harris first reported transient idiopathic trigeminal sensory neuropathy in 1935, although it later appeared that, in some of his patients, this condition evolved to typical chronic and painful trigeminal neuralgia. The patients who were later described by Hill and Hughes suffered a combined motor-sensory Vth cranial nerve dysfunction, and most cases reported by Spillane and Wells developed sustained permanent trigeminal neuropathy. The largest reported series of pure trigeminal sensory neuropathy includes 10 adults with varying degrees of sensory disturbance confined to all three nerve divisions. These patients experienced no facial pain or motor deficit, and 5 (50%) recovered completely within a few months. It is estimated that typical trigeminal neuralgia occurs in about 1 in 25,000 of the population and is uncommon prior to the third decade, with 1% of the cases occurring before the age of 20 years. To our knowledge, we present the first clinical report of idiopathic trigeminal sensory neuropathy occurring in childhood.

LEMS is a presynaptic neuromuscular junction disorder typically associated with small cell lung carcinoma. The characteristic electrophysiological abnormality is a low amplitude compound muscle action potential that shows a marked increment after short maximal contraction or brief tetanic nerve stimulation. Here we describe 3 patients who had LEMS in association with lymphoproliferative disorder. The first patient had Castleman's syndrome with typical clinical and electrophysiological features of LEMS, which responded partially to treatment with 3-4-diaminopyridine. The second patient was a 7-year-old boy who had an unusual acute onset of LEMS associated with relapse of his Burkitt's leukemia. The third patient was a 60-year-old woman with non-Hodgkin's lymphoma. These 3 patients (together with 6 additional patients identified in the literature) lead us to suggest that lymphoproliferative diseases are another, hitherto unrecognized, type of malignancy associated with LEMS. Thus, any patient with these malignancies and unexplained muscle weakness should have electrophysiological evaluation for LEMS.

The present study describes the use of simple video games for a 5-week regimen of respiratory muscle training in 15 patients with Duchenne muscular dystrophy (DMD) at various stages of the disease. The games were re-arranged to be operated and driven by the respiratory efforts of the patient and to incorporate accurate ventilation and time measurements. Improvement in respiratory performance was determined by maximum voluntary ventilation (MVV), maximal achieved ventilation (VEmax) during a progressive isocapnic hyperventilation manoeuvre (PIHV) and the PIHV duration. The actual training period was 23 +/- 4 days (mean +/- S.D.) at ventilatory effort of 46 +/- 6% MVV, for 10 +/- 3 min day-1. Patients with moderate impairment of lung function tests (LFT) showed an improvement in MVV, VEmax, and duration of PIHV of 12 +/- 7% (p < 0.02), 53 +/- 25% (p < 0.001) 57 +/- 21% (p < 0.01), respectively. Improvements correlated with actual training time and ventilation level, %MVV, but negatively correlated with years of immobilization and with the initial MVV. We conclude that computerized respiratory games may be applied for breathing exercises and may improve respiratory performance in recently immobilized children with DMD who have moderate impairment of LFT.

A 15-month-old boy, thought to have a congenital myopathy, was subsequently diagnosed as having mucolipidosis type IV, with typical membranous inclusions in muscle fibers. Involvement of skeletal muscle in this lysosomal storage disease may explain the motor delay and hypotonia that are its most common presenting signs.

The development of neuromotor patterns in relation to birth weight was studied in the rabbit, a perinatal brain developer. In order to induce intrauterine growth retardation and to increase the number of low birth weight rabbits, experimental ischemia to half the fetuses in each doe was achieved by total ligation of approximately 30% of spiral vessels to the placenta, during the last trimester of gestation. Following natural delivery, the rabbit pups were periodically observed for the appearance of eye-opening and righting reflex, and for the cessations of falling, circling and dragging of hind limbs. An index of neuromotor development was assigned to each rabbit by summing up the age (in days) of appearance of each of the neuromotor milestones. An association was found between low birth weight and delayed neuromotor development at 2 weeks of age. The most significant correlation was found between low birth weight and delayed disappearance of falling. The latter may represent incoordination as an expression of cerebellar dysfunction.

A one-month-old infant with chronic diarrhea, staphylococcus septicemia, otitis, mastoiditis, and malnutrition was treated by intravenous alimentation and multiple antibiotics. He developed an abscess at the site of an intrajugular indwelling plastic catheter, from which Candida was grown. He died suddenly with signs of endocarditis with embolization. Autopsy revealed disseminated candidiasis, endocarditis with large candidal vegetations on all valves, with multiple granulomata and microabscesses in the brain. The possible role of indwelling plastic catheters, mastoiditis, malnutrition, and antibiotics in the pathogenesis of disseminated candidiasis in infants is discussed. Candida endocarditis is very rare in children, and this case is the fourth to be reported in the literature.

Acute disseminated encephalomyelopathy and Guillain-Barré syndrome are both immunologically mediated para-infectious demyelinating disorders, the former affecting the central nervous system and the latter affecting the peripheral nervous system. The term encephalo-myelo-radiculo-neuropathy was introduced to describe cases in which major involvement of one system, most commonly the peripheral, was associated with mild involvement of the other. We present a case of acute severe demyelination simultaneously affecting both the central and the peripheral nervous systems in a 10-year-old female. This clinical picture combines acute disseminated encephalomyelopathy and Guillain-Barré syndrome, both of which are extremely severe.

Two sisters are described. They are offspring of Arabic parents who are both first and second cousins, through both sets of grandparents; additionally the father9s parents are first cousins. The diagnosis of agenesis of the corpus callosum in the propositae was made by the characteristic picture on the pneumoencephalogram. The clinical symptoms in the two sisters varied considerably. The older sister had shown delayed psychomotor development in infancy, mild mental retardation, and developed seizures at 7 years of age of both the grand mal and akinetic types. Her physical and neurological examination did not show any abnormalities. The EEG was severely abnormal with slow wave activity over the posterior parts of the brain and focal spiking. The younger sister presented at 6 months of age with failure to thrive, generalized hypotonia, but without seizures. Her EEG was within normal limits. This anomaly was probably transmitted by an autosomal recessive gene. The clinical and genetic aspects of this syndrome are discussed.

The occurrence of Zollinger-Ellison syndrome and neurofibromatosis in the same patient has theoretic and practical implications. It was believed that the overlap between MEN-I and MEN-2 was restricted to the parathyroid glands. Recently, however, several reports have described patients in whom characteristics of both MEN conditions existed ..-o The findings in our patient support the concept of a relationship between MEN-I and MEN-2. Adult patients with neurofibromatosis and hypertension are likely to have pheochromocytoma, but renal artery stenosis is a more common cause for hypertension in young patients with neurofibromatosis." We were unable to demonstrate a pheochromocytoma or renal artery stenosis in our patient. After total gastrectomy, the urinary vanillylmandelic acid content decreased abruptly, and the blood pressure and heart rate returned to normal limits. We cannot explain these changes. A similar return to normal of the blood pressure was described by Tomlinson," who reported that a hypertensive patient with the Zollinger-Ellison syndrome, a pituitary tumor, and hyperparathyroidism became normotensive after total gastrectomy and parathyroid resection.

An infant presented with congenital hypotonia, poor sucking, apathy, and areflexia. Muscle biopsy at two months of age revealed numerous nemaline rods, suggesting congenital nemaline myopathy. During the ensuing months, familial dysautonomia was suggested by recurrent pulmonary infections, dysphagia, alacrima, hyperhydrosis, emotional lability, and unexplained episodes of hyperthermia and breath-holding spells. The diagnosis was confirmed by positive intradermal histamine and ocular mecholyl tests. The finding of nemaline rods adds a new facet to the recognized polymorphic presentation of familial dysautonomia.

Vitamin E levels were measured in the plasma of infants and children with various neuromuscular disorders. Seven of 8 infants with Werdnig-Hoffmann disease (WHD) had a significantly lower plasma vitamin E level (p less than 0.01) than age-matched normal controls, children with congenital myopathies, or children with muscular dystrophy. Vitamin E deficiency in WHD is not caused by malabsorption. A therapeutic trial of vitamin E in 3 patients with WHD did not change the natural course of the disease. Vitamin E deficiency may play a role in the pathogenesis of WHD.

SYNOPSIS A case of transient global amnesia in a nine year old child with a history of recurrent episodes of vertigoand a family history of migraine headache is described. The possibility that acute confusional state inchildren, presenting as transient global amnesia may represent a variant of basilar migraine is discussed.

To the Editor.— In the February 1977Archives(34:114-115, 1977), we described an infant who had severe generalized congenital hypotonia, in whom selective myosin degeneration was found in a muscle biopsy specimen. During the following year, we reexamined the girl and performed another biopsy on her contralateral quadriceps femoris muscle. We would like to report here the benign course of this disorder. During the second year of life, the infant showed great improvement in motor performance. At 1 year of age, she was able to stand against the wall and walk with assistance. At 15 months of age, she learned to roll over and to sit up. At 18 months of age, she was able to get up from the floor and walk unassisted. At 27 months of age, she still had a positive Gowers' maneuver and tired easily. The results of a Bayley development test showed a two-month delay