Beevor's sign and facioscapulohumeral dystrophy.

We have frequently observed that Beevor's sign was present in patients with facioscapulohumeral dystrophy (FSHD) but absent in patients with other neuromuscular disorders. To determine the significance of this observation we prospectively evaluated 30 patients with FSHD and 40 patients with other neuromuscular disorders. Beevor's sign was present in 27 of 30 patients with FSHD but absent in all 40 control patients. We conclude that Beevor's sign is a common finding in patients with FSHD even before functional weakness of abdominal wall muscles is apparent. Testing for Beevor's sign is a simple screening test that may help in distinguishing FSHD from other forms of facioscapulohumeral syndrome.

The treatment of Friedreich's ataxia with amantadine hydrochloride.

Amantadine hydrochloride (AH) was orally administered to 16 patients with Friedreich's ataxia. We evaluated patient response with the functional ataxia scoring scale and calculated a total disability score. The mean percent improvement of the total disability score was 29.5%; for ambulatory patients alone it was 45.5%. No significant side effects were encountered. AH appears to be a safe and effective symptomatic treatment of Friedreich's ataxia.

Lissencephaly: fetal pattern of glucose metabolism on positron emission tomography?

BACKGROUND: In classical lissencephaly, the cerebral cortex is four-layered, containing neurons that have failed to complete their migration between 12 and 16 weeks of gestation. METHODS: The authors studied the functional activity of lissencephalic cortex using 2-deoxy-2[(18)F]fluoro-D-glucose PET (FDG PET) in eight patients (six girls and two boys, mean age 7.5 years) with isolated lissencephaly sequence. RESULTS: The PET scans revealed a remarkably similar and bilaterally symmetric pattern of glucose metabolism in all eight patients. The cerebral cortex of lissencephaly showed two layers that could be differentiated based on metabolic activity. The inner layer, which probably corresponds to the inner cellular layer of lissencephalic cortex, showed 8 to 63% higher glucose utilization rate than the outer layer, which probably represents a composite of the molecular, outer cellular, and cell-sparse layers. Patients with a higher metabolic ratio between the cortical layers (inner/outer) showed greater delay in communication (p = 0.007) and socialization (p = 0.03). CONCLUSIONS: These findings are consistent with [(14)C]-2-deoxyglucose autoradiography studies in fetal sheep that have shown that before the development of significant numbers of axons, dendrites, and synapses, glucose metabolism appears to be highest in regions with the highest density of cell bodies, compared to the more mature state when glucose metabolism is highest in areas of greatest dendritic arborization. FDG PET studies of classical lissencephaly provide a different perspective in the analysis of brain gyral anomalies than those with traditional neuroanatomic imaging techniques.

Pulmonary function and ventilatory response to chemical stimuli in familial myopathy.

We studied the pulmonary function and ventilatory response to carbon dioxide and hypoxia in three sisters aged 16, 13, and 10 years who presented with droopy eyelids, external ophthalmoplegia, hearing loss, speech difficulty, and truncal muscular weakness. Pulmonary function test results showed decreased maximum static pressure, reduced vital capacity and total lung capacity, normal functional residual capacity, elevated residual volume, and reduced dynamic pulmonary volumes. The degree of functional abnormality paralleled the severity of clinical manifestations. The characteristic picture of pulmonary functional abnormality was distinct from either restrictive disorders of pulmonary origin or obstructive pulmonary diseases. The ventilatory response to hypoxia was markedly diminished and hypercapnic response was moderately diminished in all three patients.

Colpocephaly in identical twins.

Colpocephaly is congenital disproportionately enlarged occipital horns of the lateral ventricles. It is easily recognized on computed tomography, magnetic resonance imaging or cerebral ultrasonography. The first report of colpocephaly in identical twins is presented. This is also the first reported instance of above normal intelligence occurring in conjunction with colpocephaly. The associated anomalies found as mirror images in these twins imply a genetic basis for their colpocephaly.

Otocerebral anomalies associated with topical tretinoin use.

Topical preparations of tretinoin are used for the treatment of various skin conditions and for rejuvenation of the skin. Published information on pregnancy outcome following maternal exposure to topical tretinoin is limited to three case reports. We report a case of a patient with anomalies involving the ear and central nervous system with exposure to topical tretinoin during the first trimester. Though the potential link between the use of topical tretinoin and the existence of fetal malformations remains to be further documented by animal as well as epidemiological studies, we strongly recommend that the use of topical tretinoin during pregnancy should be discouraged, and effective contraception should be used in patients of childbearing age.

Nitrazepam-induced cricopharyngeal dysphagia, abnormal esophageal peristalsis and associated bronchospasm: probable cause of nitrazepam-related sudden death.

Nitrazepam was used in the treatment of resistant myoclonic epilepsy in 38 children. After the occurrence of nitrazepam-associated swallowing incoordination, high-peaked esophageal peristalsis and related bronchospasm in one patient, we initiated a prospective study of esophageal manometry using a station pull-through technique with a pediatric 4-channel continuous perfusing system. Three more patients were found to have delayed cricopharyngeal relaxation and high-peaked esophageal peristaltic waves. The initial patient developed severe respiratory distress and bronchospasm necessitating ventilatory support while on nitrazepam and improved dramatically with subsequent normal manometric study following nitrazepam discontinuation. Nitrazepam was reintroduced for its anticonvulsant and cognitive benefits and was tolerated at a reduced dosage. We postulate a central nervous system effect of nitrazepam promoting parasympathetic overactivity or vagotonia which can cause potentially fatal respiratory distress. Care must be exercised in nitrazepam use and esophageal manometry may be helpful in defining patients at greater risk for sudden death.

Hyperekplexia and sudden neonatal death.

Fifteen patients with hyperekplexia were identified in 3 families; diagnostic clinical characteristics were defined which allowed for early recognition and treatment. During the first 24 hours of life, spontaneous apnea and sluggish feeding effort were observed. After the first 24 hours, surviving infants exhibited the hyperekplexic startle response to nose tapping. This startle response is characterized by sudden muscular rigidity, feeding-induced oropharyngeal incoordination, and poor air exchange often with apnea, persisting with repetitive nose tapping. Untreated infants experienced recurring apnea until 1 year of age. Three of 15 patients died unexpectedly during the neonatal period. Patients treated with clonazepam (0.1-0.2 mg/kg/day) had no serious apneic episodes and startle reflexes were diminished. The pathophysiologic mechanism for hyperekplexia remains obscure. Electroencephalographic studies were consistently normal. The response to and tolerance of benzodiazepines are striking in newborns and infants and suggest an aberrant central nervous system reflex as the etiology; therefore, hyperekplexia should be considered in the evaluation of neonates and infants with apnea, aspiration pneumonia, episodic muscular rigidity, hyperexcitability, and near-miss sudden infant death syndrome. The need for immediate monitoring of at-risk infants, observation for signs of hyperekplexia, and initiation of clonazepam in these patients are emphasized. Hyperekplexic startle response to nose tapping should be included in the routine examination of all newborns.

XY sex reversal and a nonprogressive neurologic disorder: a new syndrome?

We report a patient with a unique combination of clinical findings: XY sex reversal, spastic paraplegia, mental retardation, dysmorphism, and infantile-onset olivopontocerebellar hypoplasia. The phenotype of our patient did not coincide with any of the described forms of XY reversal syndromes, hereditary or sporadic spastic paraplegias, or congenital or infantile-onset cerebellar or olivopontocerebellar atrophies or hypoplasias. The disorder of this patient likely represents a genetic condition with pleiotropic effects on brain development and sex determination and adds further evidence for the heterogeneity of spastic paraplegia/infantile olivopontocerebellar hypoplasia syndromes and sex reversal syndromes.

Childhood lumbosacral plexus neuropathy.

Primary lumbosacral plexus neuropathy without underlying disease is a well-defined syndrome characterized by pain, weakness, and atrophy in the distribution of the lumbosacral plexus. It generally affects adults and rarely occurs in children. We report 2 children with primary lumbosacral plexus neuropathy evaluated at our institution and review the literature. This syndrome, despite initially severe symptoms, appears to be benign with a favorable prognosis in children.

High-dose intravenous immunoglobulin therapy in juvenile myasthenia gravis.

Autoimmune neurologic disease management has been significantly modified by the use of high-dose intravenous immunoglobulin (HDIVIG) during the past 15 years. Venous access, readily available IgG (until recently), and the relative lack of serious identifiable complications have prompted its use in myasthenia gravis. In adults, its effectiveness has been inconsistent, with variable acetylcholine receptor (AChR) antibody responses. Ten children were evaluated for clinical responses to, and complications of, HDIVIG. Weekly anti-AChR antibody titers in three patients were obtained. The HDIVIG dosage was 2 gm/kg body weight, infused at variable rates of 2 gm/kg for 1 day, 0.66 gm/kg daily for 3 days, and 0.5 g/kg daily for 4 days; in one patient the total dose was 0.8 gm/kg to correct to the ideal body weight. All children but one tolerated HDIVIG without complications. Eight patients exhibited definite improvement in functional strength after HDIVIG, but a decreasing response to HDIVIG was evident after multiple monthly treatments, warranting the additional use of corticosteroids in two patients. A decrease in anti-AChR antibody levels was observed in the three patients tested, but this decrease was constant in one patient. No correlation was observed between clinical response and antibody titers. HDIVIG is safe and effective in most patients for short-term management of juvenile myasthenia gravis, in myasthenic crises, and in preparing patients for surgery but appears to be of limited long-term benefit.

Partial cytochrome b deficiency and generalized dystonia.

An 18-year-old female had clinical features of idiopathic torsion dystonia with bilateral hypodense putaminal lesions on computed tomography. Mitochondrial encephalomyopathy was suspected because of persistent lactic acidemia and myopathy. Studies of oxidative metabolism on isolated skeletal muscle mitochondria revealed partial cytochrome b deficiency indicating a defect in the cytochrome b- c1 complex. This finding represents a unique, multisystem syndrome of progressive dystonia, putaminal degeneration, myopathy, and mitochondrial cytochrome b deficiency. Mitochondrial metabolic disorders may be a cause of torsion dystonia when other known associated factors are absent.

Muscle and nerve biopsy in the evaluation of neuromuscular disorders: the surgeon's perspective.

BACKGROUND/PURPOSE: A muscle biopsy frequently is requested by the neurologist evaluating a child with neuromuscular symptoms. However, there are no reports discussing the preoperative evaluation for, and diagnostic yield of, this procedure. The authors reviewed our experience over a 10-year period to obtain these data. METHODS: The records of 153 patients who underwent muscle biopsy were reviewed with particular attention to the cardiology evaluation, the pathology report, and any resultant change in diagnosis and treatment of the child. RESULTS: All 153 specimens contained adequate tissue for complete histological analysis. Preoperative cardiology consults were obtained in 82% of the children, with abnormalities found in 9%. Severe cardiac dysfunction was found in three children, all of whom had a previously diagnosed cardiomyopathy or dysrhythmia. No pathological abnormality was found in 41% of the muscle biopsy specimens, and nonspecific pathological findings were described in 23%. A specific diagnosis was made in 36%. Only 19% of the children had their treatment changed by the results of the muscle biopsy. CONCLUSIONS: Muscle biopsies can be performed safely without routine preoperative cardiac evaluation. A specific diagnosis, however, may be made in less than half of the patients with a change in therapy available for even fewer.

Metastatic hypopharyngeal carcinoma mimicking necrotizing vasculitis of the skin.

Clinical features of cutaneous necrotizing vasculitis were the presenting signs of a hypopharyngeal carcinoma in a forty-three-year-old man. A definite diagnosis was established by examination of fine-needle aspiration biopsy and scalpel biopsy specimens. Among the dermatoses simulated by metastatic pharyngeal carcinoma, necrotizing vasculitis has not, to our knowledge, been reported previously.

A variant of adrenomyeloneuropathy in a family with adrenoleukodystrophy and adrenomyeloneuropathy.

A 31-year-old man was seen with addisonian crisis, followed by the abrupt onset of spastic paraparesis and peripheral neuropathy. A workup revealed adrenal insufficiency, for which the patient was aggressively treated. The workup also revealed an increase in very-long-chain fatty acids consistent with the diagnosis of adrenomyeloneuropathy. Abnormal pituitary dysfunction improved with treatment of the Addison's disease. A review of the patient's pedigree revealed two family members in whom multiple sclerosis had been diagnosed but which, in retrospect, was thought to be adrenomyeloneuropathy. No other family member was found to have Addison's disease. A sibling died at age 8 of Schilder's disease, confirming the presence of adrenoleukodystrophy as well as adrenomyeloneuropathy within this family.

Clinical improvement of the myopathy in eosinophilia-myalgia syndrome with steroids and rehabilitative therapy.

The authors report a case of eosinophilia-myalgia syndrome with a progressive neuromyopathy. Progressive weakness, myalgia, and dermatitis developed in the patient described after chronic ingestion of high-dose L-tryptophan for insomnia. Laboratory, electrophysiologic, and muscle biopsy results support the diagnosis of an inflammatory myopathy consistent with that of eosinophilia-myalgia syndrome. The patient's weakness led to wheelchair dependency. A review of the literature regarding this disorder shows inconsistent results with steroid and other modes of therapy. After a course of high-dose steroids with long-term tapering and vigorous inpatient and outpatient rehabilitation, the patient was able to walk and function independently within 2 months.

[Etiopathogenesis of malignant melanoma of the skin. I. Clinico-biological and nosologic considerations]. / Etiopatogenesi del melanoma maligno cutaneo. I. Considerazioni biologico-cliniche e nosologiche.

Melanoma incidence is rapidly increasing in several countries. This neoplasm has been consistently studied in patients with dysplastic (pleomorphic) nevus, mainly in Anglo-Saxon populations. There is no evidence that among Italians the sequence pleomorphic nervus----cutaneous malignant melanoma shares the identical pathophysiologic mechanisms with the above mentioned form. Pleomorphic nevi are generally thought to be precursors of malignant melanoma of the skin, due to their chromosomal instability. Also common acquired nevi are lesions which can exhibit, although exceptionally, chromosomal abnormalities. Consequently, the sequence pleomorphic nevus----cutaneous malignant melanoma could also include the common nevus. The clinical implications of this stand-point, however, are to be more extensively investigated.

[Etiopathogenesis of malignant melanoma of the skin. II. Disease factors inherent in the organism]. / Etiopatogenesi del melanoma maligno cutaneo. II. Fattori di malattia inerenti all'organismo.

Familial malignant melanoma with dysplastic (pleomorphic) nevus has been the most extensively investigated form of this neoplasm. Searches for dominant oncogenes and tumour recessive genes have been performed in various populations to clarify the pathogenesis of the disease. Some of the them have made in possible to localize the gene of the familial cutaneous melanoma with pleomorphic nevus on 1p chromosome. In various progression stages of this neoplasm different chromosomal abnormalities have been reported, which are only relatively specific of the disease stage. Growth substance (sex steroids, hormones, vitamins, immune factors, ions, prostaglandins, and others) regulate melanocyte proliferation and, perhaps, that of melanoma cells.

[Etiopathogenesis of malignant melanoma of the skin. III. Disease factors inherent in the environment. Pathogenetic hypothesis]. / Etiopatogenesi del melanoma maligno cutaneo. III. Fattori di malattia inerenti all'ambiente. Ipotesi patogenetica--conclusioni.

Sunlight, particularly its UVB component, is thought to be the most important environmental factor for oncogenesis of melanoma. Its intensity, at the ground level, is a positive function of altitude and a negative function of latitude. Sun exposure and susceptibility in childhood seem to be major risk factors at least in Anglo-saxon countries. UV radiations are able to act as complete carcinogen. Eumelanin/pheomelanin ratio also appears as an important risk factor. Ionizing radiations, heat and traumas have been seldom related to melanoma carcinogenesis. Several chemicals, among them drugs and toxic drugs, add to the list of possible causative agents. Loss of alleles encoding for suppressor factors, caused by UV radiation, might play a significant role in carcinogenesis. A model is proposed, for "mediterranean" vs "caledonian" melanoma, in which the phenotypic sequence melanocytic nevus----melanoma would exhibit peculiar characteristics.