Central nervous system calcifications following tap water rinsing in autopsy material from children. A pitfall.

CNS from 80 children collected consecutively at the Institute of Forensic Medicine, Aarhus, were investigated. Owing to peculiar calcifications of the first 41 CNS examined, we gradually came to suspect that some external factors had influenced the results. Different fixation methods used on the CNS, rinsed or not rinsed in tap water, led us to suggest that the relatively high calcium content in the tap water in our part of the country was the cause. The non-pathologic calcification could presumably mimic metabolic diseases.

Enzyme and protein studies of demyelination in diabetes.

Neuropathological evidence of demyelination was found in the brain and sciatic nerve of diabetic patients at autopsy. The activity of acid proteinase was somewhat increased in the white matter but decreased in the gray matter of diabetic patients. No increase was observed in the activity of neutral proteinase in diabetic white and gray matter. The activities of beta-glucuronidase and 2',3'-cyclic nucleotide-3'-phosphohydrolase (CNP) were of the same level as those of the controls. The activities of all 4 enzymes appeared to be increased in the diabetic nerve, with the possible exception of CNP which was measured from only 1 nerve. Furthermore, the amount of total protein was markedly decreased in diabetic peripheral myelin. The encephalitogenic basic protein of diabetic brain myelin was normal in the disc gel electrophoretic patterns of brain myelin proteins. However, the basic proteins of peripheral myelin were reduced in a number of diabetic patients. The present biochemical findings for diabetic white and gray matter were largely normal. Instead, the increased activities of at least the proteinases and beta-glucuronidase in diabetic peripheral nerve, together with the loss of basic proteins, indicate extensive biochemical damage of the peripheral nervous system in diabetes. They suggest that demyelination and other phenomena observed in diabetic peripheral nerve are not caused only by angiopathy and impaired circulation.

Familial progressive myoclonic epilepsy. A clinical, genetical, biochemical and patho-anatomical study of a family with a 6-year follow-up.

Six siblings, including 4 cases of myoclonic epilepsy, their parents and 2 grandmothers were subjected to systematic investigation, and the patients were followed-up. The genetic studies revealed in the mother's family a patient with Lafora bodies demonstrated at autopsy. No chromosome abnormalities were found nor any linkage to the HLA system. The affected family members were characterized biochemically by an increased excretion of total glycosaminoglycans and/or an abnormal electrophoretic pattern of urinary glycosaminoglycans with an increased proportion of low-sulfated glycosaminoglycans. In the healthy family members this pattern of electrophoresis could also be demonstrated in the father and the paternal grandmother. Based on the biochemical results and the genetic studies it is suggested that the family members with progressive familial myoclonic epilepsy present a combination of at least 2 hereditary defects. The course of the disease has been relatively benign and treatment with sodium valproate, baclofen and clonazepam has shown quite satisfying results. In consequence of the biochemical findings combined treatment with A and E vitamins has been initiated.

A neuropathological and neuropsychological study of Turner's syndrome.

A neuropathological study was made in 2 women with Turner's syndrome. Neuropsychological investigation in one of them correlated with what has previously been found in Turner's syndrome as well as with the localization of the most pronounced neuropathological aberration which was of atherosclerotic nature, most pronounced in the right temporo-parietal area. These findings as well as the findings of acidophile hypoplasia of the pituitary gland are discussed.

Histological and morphometric observations on the reticular fibers in the arterial beds of patients with ruptured intracranial saccular aneurysms.

Histological and morphometric studies on the collagenous, reticular, and elastic fibers of the tunica media were performed on the middle cerebral and brachial arteries of patients with ruptured intracranial saccular aneurysms and controls. There was no difference between aneurysm patients and controls in the amount of collagenous and elastic fibers. The amount of reticular fibers was, however, reduced about 35% in aneurysm patients within both the middle cerebral artery (P less than 0.01) and the brachial artery (P less than 0.02). The reticular fibers were irregularly distributed and often appeared shorter and coarser than normally. The observations point to a generalized abnormality of the arterial bed in some patients with rupture of saccular aneurysms.

The concentration of the Na,K-pump in skeletal and heart muscle in congestive heart failure.

Na,K-ATPase (or the Na,K-pump) is essential for excitability and contractility of muscle tissue. Previous studies have shown a decrease in the concentration of this pump in endomyocardial biopsies from patients with dilated cardiomyopathy. The effect of congestive heart failure on the concentration of Na,K-ATPase in skeletal muscle was assessed in 16 patients by measurement of binding of 3H-ouabain to biopsies of the vastus lateralis muscle. Ten patients had impaired left ventricular function with an ejection fraction of 0.32 +/- 0.03 and a concentration of the Na,K-pump of 229 +/- 15 pmol/g wet weight in the skeletal muscle, whereas 6 patients had an ejection fraction of 0.66 +/- 0.05 (P less than 0.001) and a concentration of 307 +/- 17 pmol/g wet weight (P less than 0.01). In endomyocardial biopsies, the concentration of Na,K-ATPase was 340 +/- 37 and 500 +/- 39 pmol/g wet weight (P less than 0.025) in patients with impaired and normal ventricular function, respectively. There was a significant correlation between the concentration of the Na,K-pump in the biopsies of the skeletal muscle and ejection fraction, as well as between its concentration in the endomyocardial and skeletal muscular biopsies (r = 0.56, P less than 0.025 and r = 0.72, P less than 0.005, respectively). The decrease in concentration of the pump in skeletal muscle may contribute to the limitation of exercise capacity in congestive heart failure.

Cerebral magnetic resonance spectroscopy in Rett syndrome. Failure to detect mitochondrial disorder.

A total of eight girls with Rett syndrome were examined, by 31phosphorous magnetic resonance spectroscopy (31P MRS) (4 girls), proton MRS (1H MRS) (4 girls), muscle biopsying (2 girls), and determination of pyruvate and lactate in plasma (5 girls), to investigate the hypothesis of a mitochondrial malfunction as the etiology for this neurologic disorder. Almost all examinations, including electron microscopy in search of structural mitochondrial abnormalities, gave normal results, the only exception being the not unexpected finding of slight neurogenic atrophy in the muscle biopsy specimen from a 15-year-old girl.

Diffuse muscle fiber atrophy in newly diagnosed diabetes.

Muscle fiber dimensions were studied in six newly diagnosed insulin-dependent young diabetic males and in four age, sex and weight matched controls. Three of the patients had never received any antidiabetic medication before biopsy and the others had been treated with insulin for a few days only. Mean fiber caliber of the anterior tibial muscle was smaller in diabetics than in controls, the values being 61.8 +/- 4.3 micron (SD) versus 77.8 +/- 9.1 micron (2p less than 0.01). The size-frequency distribution of fiber calibers showed that a considerable part of the fiber population was reduced in size. No significant changes were found in sarcomere length, number of muscle or interstitial cell nuclei or number of capillaries. The observation of an over-all reduction of muscle fiber size following a few weeks of severe hyperglycemia is in accordance with previous experimental studies. We conclude that the catabolism associated with a sustained and uncorrected diabetic state in man leads to muscle fiber atrophy.

Prader-Willi syndrome and central nervous system calcifications: chance or fundamentally related findings?

The central nervous system of a 16 8/12-year-old boy with Prader-Willi syndrome is described. Extensive calcifications of the central nervous system were observed at autopsy as grittiness of the brain slices and verified by X-ray and microscopy. The encrustations were particularly localized in the leptomeninges, the first and second layer of the cerebral and cerebellar cortex and along the ventricular system. We suggest that the alterations are nonspecific and perhaps secondary to a fundamental metabolic disorder in the central nervous system.

Preservation of the nucleus X-pelvic floor motosystem in amyotrophic lateral sclerosis.

Fourteen cases of amyotrophic lateral sclerosis (ALS) were investigated neuropathologically, emphazising the sacral spinal cord which contains Onuf's nucleus X. The nucleus innervates the pelvic sphincters. In two cases, small striated pelvic muscles were studied. No changes characteristic of ALS were observed in Onuf's nucleus X, not even in 8 cases in which other caudal motoneuron nuclei presented a severe loss of neurons. The striated sphincters proper demonstrated no signs of neurogenic atrophy in contrast to muscles in the limbs. The bulbo- and ischiocavernosus muscles, also supposedly innervated by Onuf's nucleus, were without pathological changes. Moreover, the latter two muscles were found to have a composition very similar to that of the sphincters. This indicates that a characteristic morphology of the nucleus X-innervated muscles exists. A review of the clinical records of all the cases revealed, that although 8 demonstrated severe involvement of the lower extremities, only one presented vesico-rectal dysfunction which could be ascribed to ALS. But even in this case, the pelvic closure mechanisms appeared to be intact. The preservation of continence in ALS is related to the neuropathological findings, and the observations are compared with previous neuropathological studies concerning Onuf's nucleus X as well with experimental studies including this nucleus. It is pointed out that structural and biochemical differences must exist between nucleus X neurons and other motoneurons.

Dorsal root gangliopathia presenting with rapidly progressing sensory polyneuropathy.

A 52-year-old woman developed progressive sensory polyneuropathy leading to death in 1.5 years. Electromyography and peripheral nerve biopsy had revealed severe axonal degeneration. Neuropathological examination showed involvement of all dorsal root ganglia with loss of the bipolar nerve cells, degeneration of the remaining nerve cells, Nageotte's residual nodules, and scattered lymphocytes. The posterior columns of the spinal cord and the sensory spinal roots revealed secondary loss and degeneration of the nerve fibers. The etiology is unknown but an autoimmune-mediated reaction effecting the nervous system is strongly suggested.

Incomplete development of the brain in a newborn with methylmalonic aciduria.

The investigation of the brain from a seven-day-old girl who died from a disorder in the metabolism of methylmalonic acid revealed a severe reactive gliosis of the cerebral white matter and the deeper layers of the cortex, incomplete development of the fetal granular layer of the cerebellum and the Bergmann glial cells, and delayed myelination of the cerebellum, the brainstem, and the cervical spinal cord. We suggest that some of the described neuropathological findings are an immediate consequence of a disturbed methylmalonic acid metabolism starting in utero, and not exclusively a secondary phenomenon due to accumulation of metabolites and acidosis postpartum.

Late nervous system disorders in cured malignant lymphoma: a clinical and neuropathological study.

A 53-year-old woman was treated for and cured of low grade malignant lymphoma, localized to the neck, by irradiation and chemotherapy. One year later she developed signs of damage to the spinal cord with slight paraparesis of the lower extremities, which remained stationary for seven years. Then, new and rapidly progressive central and peripheral neurological symptoms developed. About one year later the patient died. At autopsy a malignant glioma of the right temporal lobe and radiation damage to the spinal cord were found. Lymphocytic infiltrations in the peripheral nerves and muscles of the lower extremities were also seen. A severe neurogenic atrophy was present but no relapse of malignant lymphoma was found. Depressed immune defense is suggested to be the cause of the pathological changes of the nervous system in this case. The inflammation of the peripheral nerves might be due to activation of a latent virus infection.

Distribution of dietary mercury in a dog. Quantitation and localization of total mercury in organs and central nervous system.

An Alsatian dog which had been fed fish contaminated with methyl mercury for 7 years was examined after its death at the age of 12, 4 years after the exposure to methyl mercury had ceased. Two dogs of the same age and breed served as controls. In the exposed dog, mercury was found in all of the organs examined; the highest concentrations were found in the kidneys, and the lowest in the gastrointestinal tract and skeletal muscles. In the central nervous system (CNS) the mercury was fairly uniformly distributed, with 93% in the inorganic state, whereas the skeletal muscles contained approximately 30% inorganic mercury. This demonstrates time-dependent demethylation and suggests a variation in the rate from one type of tissue to another. At the time of death, the mercury level in the dog was still falling. In the control dogs, detectable amounts (0.01 mg kg-1) of mercury were only found in the kidney and liver. The distribution of mercury was determined by a histochemical method (autometallography) for locating mercury in tissue sections. Sections from autometallography of the central nervous system showed large deposits of mercury in all areas of the cerebral hemispheres, the brainstem and the spinal cord, including nerve cells, astrocytes, microglial cells and vessel walls. The granular layer of the cerebellar hemispheres was especially loaded, while only a few granules were present in the Purkinje cells. In the leptomeninges the vessels and the macrophages were heavily encrusted. High amounts of histochemically demonstrable mercury were observed in the liver, thyroid gland and kidney. In the control dogs, all the organs examined were practically devoid of deposits.

Morphology of tracheal scar after resection with CO2-laser and high-frequency cutting loop. A study in normal pigs.

In 6 pigs a bronchoscopical resection of the tracheal mucosa was performed using CO2-laser on one side, and an electric high-frequency cutting loop (ECL) on the other. The pigs were sacrificed 3 months later. On macroscopic examination the tracheal mucosa appeared almost normal on the laser-resected side, while severe deformation was seen after ECL treatment. Microscopically the respiratory epithelium had regenerated irrespective of the instrument used. After laser resection the subepithelial tissue had a normal width and consisted of collagen fibrils with few vessels and sparse fragmented elastic tissue. The cartilage showed necrosis and pericellular fibrosis. The scar tissue after ECL was a broad cellular and richly vascularized connective tissue. The content of elastic fibres was markedly greater than after laser resection. The cartilage showed small irregular necroses lined by pyknotic nuclei. In neither case had the gland regenerated. Both CO2-laser and ECL caused severe (but not identical) damage to the tissue, clearly visible after 3 months. However, the deformation caused by ECL was not seen at the laser-resected sites, which makes the laser technique seem preferable--where economy permits.

Intracranial lipoma. Report of a case and differentiation from other tumours of the cerebellopontine angle.

Teratomata of the cerebellopontine angle are rare. A case of a lipoma of this localization occurring in a 50-year-old man with an interesting case history is reported. The differential diagnosis of tumours of the internal auditory meatus and the surrounding structures is discussed. In cases with an uncharacteristic clinical history suggesting involment of the VIIIth cranial nerve, it is important to focus attention on the existence of rare lesions of the internal acoustic porus. The diagnosis can only be established with operation and biopsy.