Search

This paper has given an overview of the complexity of childhood muscle disease. Fortunately, astute history-taking and physical examination, combined with readily available tests, will usually enable the clinician to formulate a diagnosis and plan of management.

The major and minor manifestations of tuberous sclerosis are reviewed and considerations for diagnosis of this complex and progressive disorder. Emphasis is placed on the extremely variable nature of tuberous sclerosis, as well as on its occasional fetal (or embryologic) onset.

The incidence of tuberous sclerosis in Rochester, MN, was 0.56 per 100,000 person-years in 1950 through 1982, and point prevalence on December 31, 1980, was 10.6 per 100,000 persons. The true incidence and prevalence may be even higher, because cases with hypomelanotic macules and no other clinical manifestations are often unrecognized. Pertinent clinical observations in the eight cases identified included familial occurrence in two; hypomelanotic macules in all eight; seizures with onset before age 2 in four, of whom two were mentally retarded; and no neurologic abnormalities in those free of seizures.

In two sets of male homozygous twins with tuberous sclerosis, one twin in each set suffered frequent generalized seizures from early life, and the second either had no seizures or had only short-lived seizures. One twin of each pair is of normal intelligence, and the other is mentally subnormal. We propose that generalized seizures occurring in early life are an important mechanism in an apparently progressive dementing process in some infants and children with tuberous sclerosis. If our assumption is correct, an early attempt to control generalized seizures in these patients is indicated even in the presence of the cortical, subcortical, and subependymal pathologic changes characteristic of cerebral tuberous sclerosis.

The renal lesion classically associated with tuberous sclerosis is angiomyolipoma. Renal cysts are less frequent, occurring alone or in conjunction with angiomyolipomas. We reviewed the records of 274 patients with tuberous sclerosis registered at our clinic. Of 95 patients evaluated for renal lesions 51 (54 per cent) had positive findings: 45 had angiomyolipomas, 17 had renal cysts and 11 had both lesions. These lesions usually are multiple and bilateral, and are diagnosed most effectively with computerized tomography or ultrasound. Surgery (10 kidneys) was done for life-threatening hemorrhage or suspected malignant lesions.

Computerized transaxial tomography (CTT) is a nonivasive roentgenologic method that demonstrates the configuration of the intracranial contents, including the cerebral parenchyma and the ventricular system. Of 207 children examined by CTT, 53 later had neuroradiologic contrast studies or neurosurgical intervention, or both, and two came to autopsy. The neuroradiologic, surgical, and pathologic findings corresponded with the CTT findings in patients with large ventricles, dupratentorial tumors, intracranial hematomas or cysts, and epidural collections. The correlation was less concordant in patients with intracranial vascular malformations or lesions involving cranial bones. CTT promises to be valuable for diagnosis of many intracranial lesions in children.

Six patients in two unrelated families had a hereditary form of sustained muscle activity of peripheral nerve origin. Although varying in severity among affected family members, the disease was manifested clinically as generalized myokymia and muscle stiffness. Motor and sensory nerve conduction velocities and results of nerve biopsy were normal. Repetitive after-discharges followed each motor nerve stimulus. Needle electrode examination demonstrated spontaneous recurrent bursts of motor unit activity. The burst activity of a motor unit occurred rhythmically (0.5 to 4 bursts per second) and independently of the activity of other units. Within a burst, the firing rate was high (150 to 300 Hz). The clinical and electromyographic abnormalities improved considerably after treatment with carbamazepine or phenytoin.

Health and safety regulation, training, and research were practically non-existent in Cuba before the Revolution in 1959. Since that time important advances have been made. Specialized inspectors, occupational physicians, and other such personnel are now trained in Cuba. An Occupational Health Institute, founded in 1976, provides training and specialized technical services, and conducts research. In 1978, a far reaching "Work Safety and Health Law" was enacted which defines the rights and responsibility of government agencies, workplace administrators, unions, and workers. Comprehensive control of toxic substances in workplaces, still at an early stage, is likely to increase in light of the new law, the growing availability of qualified personnel, and the mounting concern of public health authorities with the increasingly "developed" health profile of the population.

Muscle blood flow (MBF) was measured using the local (133)Xenon injection method in patients with Duchenne type muscular dystrophy (six), limb-girdle dystrophy (four), polymyositis (seven), and in normal controls (11). Measurements were made at rest and during hyperaemia induced by ischaemic exercise and by histamine injection. Capillary diffusion capacity was measured with the (51)Cr-EDTA method in three patients with Duchenne dystrophy and in six normal controls. Patients with Duchenne dystrophy had normal MBF during rest and during hyperaemia after exercise and significantly increased MBF after histamine injection. The capillary diffusion capacity was higher than normal, but not significantly. In limb-girdle dystrophy MBF was normal, while in polymyositis it was significantly decreased in all three circulatory states. The relevance of the findings to the proposed ischaemic aetiology of Duchenne dystrophy is considered.

Combined 2-dimensional and M-mode echocardiography was used to assess the cardiac status of 22 patients with Friedreich's ataxia, and the findings were correlated with the clinical and electrocardiographic (ECG) data. Mean age at onset of Friedreich's ataxia was 8 years (range 3 to 18); mean age at echocardiography was 18 years (range 8 to 39). Echocardiographic findings were abnormal in 19 patients (86%). The 3 patients with normal echocardiographic findings did not have cardiac symptoms, but 1 had ECG repolarization abnormalities. Concentric left ventricular (LV) thickening, the most common echocardiographic finding, was found in 15 patients (68%) and in all 15 the papillary muscles were thickened. These 15 patients had ECG repolarization abnormalities and 5 had left-axis deviation; however, only 3 satisfied ECG criteria for LV or right ventricular hypertrophy. Two of the 15 patients (9%) had symptoms of heart failure. Two patients had asymmetric septal thickening without clinical evidence of LV outflow tract obstruction; neither had cardiac symptoms, but both had ECG repolarization abnormalities. Two patients showed a dilated cardiomyopathy pattern; both had heart failure and atrial flutter. One of these patients died, and necropsy revealed 4-chamber cardiac dilatation, biventricular hypertrophy and histologic findings of diffuse interstitial fibrosis, myocellular hypertrophy and necrosis. This study revealed a wide spectrum of cardiac abnormalities in patients with Friedreich's ataxia.

Three patients had a clinical history of epileptic seizures during exercise. In all three patients, generalized epileptiform EEG abnormalities were activated by exercise, whereas none had paroxysms during resting wakefulness or during hyperventilation, and only one had a paroxysmal discharge during sleep. Advice to epileptic patients about physical activity should be based on a careful history of individual tolerance. In doubtful cases, an EEG recorded during exercise can provide evidence for an epileptic mechanism.

A female child with brachycephaly, hypertelorism, convergent strabismus, interstitial keratitis, analgesia on both sides of the face, absent corneal reflexes, and focal congenital alopecia of a zone of the occipital and posterior parietal scalp is presented. The patient also had generalized hypotonia in early life, and at age 4 years 9 months, she was found to be moderately mentally subnormal and to have severe cerebellar deficit consisting of gait and truncal ataxia. There was no clinical evidence of other cranial nerves being affected. It is postulated that the patient has a cerebellotrigeminal and focal dermal dysplasia due to a development arrest of the ectoderm, which gives rise to the alar plate of the rhombencephalon, the overlying epidermis, the motor nucleus of V, and the trigeminal placodes.

The relationship between Reye-Johnson syndrome and acute encephalopathy without fatty liver was investigated by comparing the lipid composition of liver samples obtained from five patients with Reye-Johnson syndrome, two patients with acute encephalopathy, and five controls. The mean total hepatic triglyceride concentration was increased nearly sevenfold in Reye-Johnson syndrome and slightly decreased in acute encephalopathy when compared with the mean control value. The mean total hepatic free fatty acid concentration was increased nearly threefold in acute encephalopathy when compared with the mean value in Reye-Johnson syndrome. Total phospholipid content was decreased in the liver in Reye-Johnson syndrome, and this difference was caused mainly by a diminution of the hepatic lecithin fraction. The ratio of palmitic acid to oleic acid and hepatic free fatty acids was 2.5 in Reye-Johnson syndrome, 0.7 in acute encephalopathy, and 0.8 in controls. These results suggest that, despite clinical similarities and laboratory evidence of hepatic dysfunction in both Reye-Johnson syndrome and acute encephalopathy, different pathogenic mechanisms may be responsible for the liver abnormalities found in the two syndromes.

Nineteen patients with a clinical diagnosis of tuberous sclerosis were examined with high-field-strength magnetic resonance (MR) imaging. Their ages ranged from 6 months to 12 years. In 17 cases, the MR examinations showed both subependymal nodules and multiple peripheral gyral lesions consistent with cortical tubers. Cortical tubers were more frequently demonstrated on spin-echo images obtained with a long repetition time (TR). Because the signal abnormality was located predominantly in the subcortical portion of the tubers, the terms "gyral core" and "sulcal island" were used to describe the patterns noted at MR imaging. Subependymal nodules were best seen on inversion-recovery or short TR spin-echo images, although hypointensity within the nodules consistent with calcification was present in 14 patients and was most evident on long TR spin-echo images. Computed tomographic (CT) scans that had been obtained within 3 years of MR images were available for 13 patients. Intracranial calcification was more accurately diagnosed with CT. However, MR imaging is more sensitive than CT in the detection of gyral tubers and, thus, may be better for screening family members and others in whom tuberous sclerosis is a possibility.

A new myasthenic syndrome is described in a patient whose symptoms began soon after birth and included generalized weakness increased by exertion, easy fatigability, hyporeflexia, and refractoriness to anticholinesterase drugs. Electromyography showed a decremental response at all frequencies of stimulation and a repetitive response to single nerve stimulation. Miniature end-plate potentials (mepps) were of normal amplitude but of decreased frequency. The mepp duration and half-decay time were prolonged, and prostigmine was without any addtitional effect. The quantum content of the end-plate potential was decreased due to a reduced store of quanta immediately available for release, but the probability of release was normal. Quantitative electron microscopy demonstrated a 3-fold to 4-fold decrease of nerve terminal size and reduced postsynaptic membrane density. The postsynaptic folds showed focal degeneration, and many were distended by labyrinthine membranous networks that communicated with the synaptic space. Degenerating nuclei were found in the junctional sarcoplasm. The ultrastructural localization of the acetylcholine receptor protein was normal. Acetylcholinesterase (AChE) was absent from the motor end-plates by histochemical and electron cytochemical criteria. Biochemical studies indicated total absence of the end-plate-specific 16 S species of AChE and marked decrease in total muscle AChE. A congenital defect in the molecular assembly of AChE or in its attachment to the postsynaptic membrane might represent the basic abnormality and condition the morphological and physiological alterations.

Computerized transaxial tomography is a useful test for the recognition of tuberous sclerosis when this diagnosis has not been firmly established by clinical methods. In addition, computerized transaxial tomography may demonstrate the location of obstruction in patients with tuberous sclerosis who have developed signs of increased intracranial presure. These generalizations are supported by evidence from four patients investigated by this test.

Duchenne muscular dystrophy manifested in one of girl twins. The twins were monozygous on the basis of red cell and HL antigens and skin graft compatibility. Karyotyping, including banding techniques, showed a normal number of chromosomes and a normal configuration of the X-chromosome in both twins. The twins were identical in appearance until symptoms of Duchenne dystrophy developed in one at age 4 years. The maternal uncle had classic Duchenne dystrophy; the mother and the nonmanifesting twin showed evidence of being heterozygous for Duchenne dystrophy. The phenotypic difference in monozygous twins is readily explained by lyonization of the X-chromosome after twinning has occurred. The findings substantiate the existence of Duchenne dystrophy manifesting in females with normal karyotypes.

The Lafora type of progressive myoclonus epilepsy is a rare and fatal familial disease characterized by seizures, myoclonus, and dementia. This diagnosis was confirmed in 2 patients by demonstrating the presence of intracytoplasmic polyglucosan bodies, or Lafora bodies, in the peripheral portion of the eccrine sweat gland duct. Exclusive use of the periodic acid-Schiff stain is recommended for demonstrating these diagnostic inclusions. Electron microscopy reveals fine pale-staining filaments, fine dark-staining granules, and dark-rimmed vacuoles within these non-membrane-bound inclusions. Skin biopsy is the preferred method of confirming the diagnosis of Lafora disease.

Dilation of the subarachnoid channels overlying the cerebral hemispheres, ie, external hydrocephalus, can be an early anatomic-radiologic finding in some infants with congenital communicating hydrocephalus. This structural change may progress to ventricular dilation or internal hydrocephalus. Enlargement of the subarachnoid channels appears to occur during the first stage in the development of congenital communicating hydrocephalus, which is to say that the subarachnoid compartment allows accumulation of CSF before there is significant ventricular distention, at least in some infants. When a pneumoencephalogram or a CT scan is performed at this stage, the findings may falsely suggest "cerebral atrophy." In six patients who received this grave neuroradiologic diagnosis, five subsequently developed normally and the sixth has static incoordination or clumsiness and mild intellectual deficiency.

Two patients with tuberous sclerosis are described in whom computed tomography of the head revealed areas of diffuse diminution of density suggestive of demyelination. Computed tomography is a sensitive test for the detection of intracerebral lesions in tuberous sclerosis, and the finding of areas of diminished density in the absence of evidence for tumor or ventricular obstruction correlates with the common histologic finding of diffuse demyelination. Serial studies with computed tomography are likely to determine whether such demyelination precedes the growth of hamartomas and calcification that characterize tuberous sclerosis.

We conducted postmortem magnetic resonance imaging (MRI) studies of five brains from patients with a clinical and pathologic diagnosis of tuberous sclerosis. Areas of prolonged T1 and T2 relaxation could easily be identified within the white matter subjacent to the cortical tubers despite formalin fixation and storage. The signal changes were identical to those reported in living patients with the disease. The detection of cortical tubers by MRI in two patients who were 34 and 35 years of age, respectively, at the time of death suggests that the signal changes on MRI are less affected by aging than are the low-attenuation changes on computed tomography, which are rarely identified in patients older than 27 years of age. Once the changes caused by fixation of tissues are considered, postmortem MRI is a viable investigative tool in studying tuberous sclerosis and other diseases, and it seems to correlate well with the MRI findings in living patients, as well as the gross and histopathologic changes seen at autopsy.

Liver specimens from 8 patients with Reye-Johnson syndrome, 2 patients with acute encephalopathy, and 10 patients without liver disease were analyzed for aflatoxins. An aflatoxin was obtained from the liver of one patient, a 15-year-old girl who had clinical, laboratory, and pathologic features of Reye-Johnson syndrome. Thin-layer chromatography, fluorescence emission, infrared spectroscopy, and derivatization studies characterized the aflatoxin as related structurally to but not identical with aflatoxin B1. This report is added to previous ones from Thailand, New Zealand, and Czechoslovakia in which the association of aflatoxins and fatty liver has been found in Reye-Johnson syndrome.

We have used computerized tomography (CT) to look for evidence of cerebral demyelination in children with progressive neurologic disorders. Fourteen patients with a clinical diagnosis of a demyelinating disorder were examined by CT, and five had CT findings suggesting cerebral demyelination. In two patients with a so-called myelinoclastic demyelinating disease, CT showed asymmetric, circumscribed areas of diminished radiodensity, and in three patients with a leukodystrophy, scans showed diffuse symmetric areas of low density in the centrum ovale. Autopsy examination in one patient confirmed the diagnosis of sudanophilic leukodystrophy and substantiated the abnormalities suspected from CT.

We reviewed the clinical records of all the patients examined at the Mayo Clinic who were operated on and found to have arachnoid diverticula of he cervical and thoracolumbar regions of the spinal column. Only patients whose lesion did not have a traumatic cause were selected for a study. There were 21 patients: 20 had been operated on at the Mayo Clinic and 1 was seen 43 years after surgery done elsewhere. The symptoms associated with the thoracolumbar lesions were, in order of decreasing frequency, pain, weakness, gait disorder, sensory symptoms, and sphincter dysfunction. The conditions associated with thoracic arachnoid diverticula included congenital pigmented nevus, diastematomyelia, multiple sclerosis, Marfan's syndrome, and syringomyelia.

One hundred two patients with Sturge-Weber disease who were seen at the Mayo Clinic between 1942 and 1986 were studied retrospectively to determine the difference in prognosis between unihemispheric (88 patients) and bihemispheric (14 patients) involvement. Seizures occurred in 63 with unihemispheric involvement and 13 with bihemispheric; the mean age at onset of seizures was 24 months in the former and 6 months in the latter. Of the total group, 19% were severely or moderately mentally retarded, 27% were mentally retarded but educable, and 45% had average intelligence. In the bihemispheric involvement group, 46% were severely or moderately mentally retarded, 38% were retarded but educable, and only 8% had average intelligence. Bilateral involvement of the brain by Sturge-Weber disease is associated with earlier onset of seizures and worse prognosis for mental development compared with unilateral involvement.

We report observations made on 149 patients with juvenile myasthenia gravis studied from onset of disease for as long as 40 years. Median follow-up was 17 years; minimum was 4 years. Eight other patients with congenital myasthenia gravis were studied separately. Of the juvenile myasthenic patients, 85 (57%) underwent thymectomy because of diseases severity. In juvenile myasthenia gravis, a spontaneous remission rate of 22.4 per 1,000 person-years was observed, regardless of disease duration. A remission rate of 260 per 1,000 person-years was seen during the first year after thymectomy, with a rate of 95 per 1,000 person-years during the next 2 years. Early surgery, presence of bulbar symptoms, absence of ocular signs or generalized symptoms, onset of symptoms between ages 12 and 16, and presence of other immune disease were associated with increased postoperative remission rates. Epilepsy (4 patients) and neoplasia (7 patients) were the most frequent associated nonimmune disorders; rheumatoid arthritis (5 patients), juvenile-onset diabetes mellitus (3 patients), asthma (3 patients), and thyroid disease (3 patients) were the most frequent associated immune diseases.

Tumors of the pineal region account for 3% to 8% of pediatric intracranial tumors. The treatment of such tumors has been in a state of flux between conservative therapy (cerebrospinal fluid shunting and radiotherapy) and direct surgical removal. A brief history and review of the literature with analysis of both approaches is given, and the Mayo Clinic's experience with conservative treatment of tumors in the pineal region in patients 20 years old and younger (27 cases) is studied and analyzed. The series comprises 21 boys and six girls, with an age range of 1 to 20 years (mean 13.7 years). Follow-up examinations are complete and range from 1 to 24 years, with a mean follow-up period of 7.8 years. The median survival time for these patients treated with shunt and radiotherapy is 17.7 years. There was no mortality from treatment and complications were rare. The details of the clinical presentation, diagnostic findings, pathology, therapy, recurrence, and survival are presented. All patients under 6 years of age (six cases) had recurrences, 50% in other areas in the brain and 50% in the spinal cord, perhaps pointing to the need for whole-brain and spinal-axis irradiation in patients in this age group. The results of this study of the conservative approach form a standard against which results of any other type of therapy may be compared.

Abnormalities of the cerebral arteries and the aorta are more common in young patients with tuberous sclerosis than in the rest of the population. Strokes have been reported but there is no confirmation that embolization of cerebral arteries by fragments of cardiac rhabdomyoma plays a role in the higher incidence of strokes in these patients.

Retinal lesions in 116 patients with tuberous sclerosis included three types: the relatively flat, semitransparent, non-calcified tumors; the more commonly described nodular, calcified tumors; and a third lesion that possessed features of the other two. Other less definite pigmented and plaque-like lesions also were seen. The evolution of a relatively flat, noncalcified lesion into an elevated nodular, apparently calcified lesion during an interval of two decades was photographically recorded.

All primary intracranial neoplasms diagnosed between 1935 and 1964, inclusive, in the well-defined populations of children under age 15 residing in the state of Connecticut and the city of Rochester, Minnesota, formed the basis for this study. The tumors occurring in this group were characterized by histologic type and by the patient's sex and the age when the tumor occurred. In Connecticut, over the 30-year period, a primary intracranial neoplasm was diagnosed in 380 patients in a mean population of 582,286 children, yielding an average annual incidence rate of 2.17 cases/100,000 population per year. Of the microscopically confirmed tumors, the most common, in order, were medulloblastoma (24.2%), astrocytoma (20.6%), glioblastoma (20.3%), ependymoma (6.5%), craniopharyngioma (5.6%) and meningioma (4.6%). These figures contrast sharply with the corresponding frequency of these tumors in the adult Connecticut population. In Rochester during the same years, 12 primary intracranial neoplasms occurred in a mean population of 7,981 children, yielding an average annual incidence rate of 5.01 cases/100,000 population per year.

Thirty-four patients with pathologically confirmed primary pineal tumors were evaluated at the Mayo Clinic from 1923 through 1976. All tumors were of germ cell or pineal cell origin. Most patients were adolescent boys with subacute increased intracranial pressure and Parinaud's syndrome. Hypothalamic symptoms were surprisingly infrequent. Direct surgical intervention was associated with high mortality, but has been more successful in recent years.

Although subacute sclerosing panencephalitis (SSPE) often presents with a characteristic EEG pattern, a 13-year-old boy with a confirmed diagnosis of SSPE had several EEG features that are unusual for this condition, namely, generalized sharp and slow wave (slow spike and wave) discharges during the waking record, an electrodecremental pattern associated with clinical seizures, and activation of the typical periodic complexes of SSPE only during sleep.

Reye-Johnson syndrome was found in 17 patients in a retrospective study of 235 children with acute encephalopathy seen at the Mayo Clinic in the period 1955 through 1971. Eight of the nine patients under 4 years of age developed the syndrome prior to 1968; eight children 10 to 15 years of age acquired the disorder from 1968 through 1971. Seven patients were admitted during the month of February. Prodromal symptoms preceded the encephalopathy in 13 patients. Eight patients had seizures. Progressive deterioration with brainstem signs led to death in 15 patients. Electroencephalographic findings correlated well with the clinical course and eventual outcome. However, no correlation was found between seizure activity and the electroencephalogram. Autopsy findings in 14 cases included cerebral edema, tonsillar herniation, hypoxic neuronal degeneration, and fatty inflitration of the liver and kidneys.