Polyglucosan bodies in brain tissue: a systematic study.

The relation between age, sex and presence of polyglucosan bodies in the brain has been systematically studied in 64 patients who did not suffer from neurological brain disorders and in 2 cases with Lafora's disease. In the normal brain the number of polyglucosan bodies is related to increasing age. Under the age of 40, polyglucosan bodies can be found sporadically in cases without a neurological disorder, but in the cases of Lafora's disease their number is uncomparatively higher. A sex relation has not been found.

X-linked ataxia, weakness, deafness, and loss of vision in early childhood with a fatal course.

An X-linked recessive disease with, in almost all patients, a fatal course in early childhood, occurring in a five-generation family is described. The 12 affected boys had early-onset floppiness, ataxia, liability to infections especially of the upper respiratory tract, deafness, and later, a flaccid tetraplegia and areflexia. Eleven boys died before the age of 5 years. One boy is still alive at the age of 12 years, but in addition to the above-mentioned signs, he must be ventilated at night and is nearly blind due to optic atrophy. In the only patient whose central nervous system could be examined at the time of autopsy, an almost complete absence of myelin in the posterior columns of the spinal cord was found. This may be the main pathological substrate for the neurological findings. No biochemical or immunological defects were detected. The family also counted 16 healthy male siblings and 13 definite of 28 possible female carriers. Some carriers developed a hearing impairment in early adulthood. As far as is known now, this disease has not been described before.

Histologic factors in the grading and prognosis of astrocytoma grade I-IV.

The prognostic value of histologic or cytologic features were examined in 317 patients with an astrocytic glioma. Of 46 features examined 7 morphologic characteristics of nucleus and 5 of mesenchyma correlated well with grading according to Kernohan. The morphological characteristics of nucleus are cellularity, atypical nuclei, polymorphism, multinucleated cells, hyperchromasia, gigantic nuclei and mitosis. For mesenchyma these were vascularity, vascular endothelial proliferation, vascular glomeruli, necrosis with palisade formation and necrosis without palisade formation. Scoring of these items on a scale from 0 to 4 enables us to establish a nucleus-score (max. 28) and a mesenchyma-score (max. 20). Nucleus-score + mesenchyma-score less than or equal to 10 corresponds with astrocytoma grade II, less than or equal to 20 with grade III and greater than 20 with grade IV. A low nucleus-score in grade II (less than 5) predicts a long survival (greater than 10 years), a high nucleus-score a low survival (median 0.6 year). In grade III a low mesenchyma-score predicts a median survival of 1.25 years, a high mesenchyma-score a median survival of 0.38 year. This retrospective study shows that nucleus-score and mesenchyma-score correlate to grading according to Kernohan and are highly correlative to survival.

Long-lasting epidural sensory blockade by n-butyl-p-aminobenzoate in the terminally ill intractable cancer pain patient.

An aqueous suspension of n-butyl-p-aminobenzoate (BAB), a highly lipid-soluble congener of benzocaine, was applied epidurally in terminally ill cancer patients with intractable pain. The suspension consisted of 10% BAB and 0.025% of the nonionic surfactant polysorbate 80 in 0.9% sodium chloride. Twelve consecutive patients received epidural BAB because pain was uncontrollable either by palliative radiotherapy or oral or epidural administrations of analgesics. The catheter or injecting needle was positioned at the segmental level of the pain. Repeated epidural injections were administered. In all patients, long-lasting sensory blockade (segmental analgesia) occurred, accompanied by a marked reduction or even absence of pain. In all patients, treatment with epidural opioids, alone or combined with local anesthetics, was no longer necessary. Five of the 12 patients did not require further administration of oral opioids. Motor, bowel, and bladder function were well preserved. In 6 patients, extensive necropsy of the spinal cord and spinal nerves did not reveal pathomorphologic changes. The outer aspect of the dura showed signs of focal necrosis on microscopy, yet its collagen structure and thickness were unchanged. Epidurally, focal infiltrative reactions were seen. The epidural use of an extremely lipid-soluble--hence hydrophobic--local anesthetic, with an exceptionally low pKa (2.3), formulated in suspension of the base, is conceptually innovative and needs further investigation. The authors conclude that the epidural administration of a BAB suspension may be an effective alternative to the neurolytic agents alcohol and phenol and may replace procedures such as cordotomy. Further investigation to determine the safety of BAB in this patient group appears warranted.

[Postoperative irradiation in grade III and IV astrocytoma]. / Postoperatieve bestraling bij astrocytoom graad III en IV.

The aim of this paper is to contribute to the discussion on the value of postoperative radiotherapy in patients with astrocytoma grade III-IV. One hundred and fifteen of the 243 patients with histologically proven astrocytoma grade III-IV received postoperative radiotherapy at the St. Radboud University Hospital Nijmegen. According to the protocol all patients with a fairly good performance status were irradiated. The extent of surgery consisted of biopsy alone in 11%, subtotal tumour resection in 85% and macroscopically complete tumour removal in 4%. All patients received a whole brain irradiation of 40 Gy with a boost of 10-15 Gy in the tumour. Patients with grade III who underwent surgical resection had a median survival of 2.1 months, those with grade IV 2.7 months. Patients who underwent surgical resection and radiotherapy had a median survival of 12 months (grade III) and 8.6 months (grade IV). The extent of surgery and grade of malignancy were the only prognostic factors. Because of the selection of patients this study produces no additional arguments in favour of postoperative radiotherapy. However, we continue our treatment strategy to irradiate patients with grade III-IV tumours because the median survival obtained with this strategy is high in comparison with data from literature.

Myelopathy due to cervical spine rheumatoid arthritis. A case report.

A 62-year-old woman with cervical myelopathy due to cervical spine rheumatoid arthritis is presented. Transoral decompression of the spinal cord, followed by posterior spine fusion in the same session was performed with good results. Unfortunately she died 3 months later due to cardiovascular disease. Clinical, radiological, surgical and autopsy data are presented.

Lafora disease: a quantitative morphological and biochemical study of the cerebral cortex.

Morphological and biochemical studies were performed on a brain biopsy from a patient with typical Lafora disease. Qualitative morphological investigation of the cortex showed that the Lafora bodies were most abundant in layers III and V of the cerebral cortex. They were exclusively located in the neurons and their processes. Quantitative morphological investigation of the cerebral cortex revealed abnormalities of the pyramidal cells of layers III and V. The neurons were often slightly atrophic. There was a reduction in the number of dendrites, in maximal dendritic length, and in the number of spines on the apical dendrites and on the side branches. Because of the biochemical study of the pyruvate metabolism of the gray and white matter of the cortex did not show abnormalities, a mitochondrial dysfunction is not likely.

Leigh syndrome, a mitochondrial encephalo(myo)pathy. A review of the literature.

Results of a literature survey of 173 patients with Leigh syndrome are presented, with emphasis on signs and symptoms in relation to age at onset, contributions of technical investigations to the diagnosis, pathophysiology, genetic considerations and therapeutic aspects. Based on this study we are of the opinion that it is possible to come to a diagnosis of "most probable Leigh syndrome" durante vitamin on the combination of clinical signs and symptoms, autosomal recessive mode of inheritance, association with a defect of energy metabolism, and CT or MRI abnormalities.

Lafora's disease. Comparison of inclusion bodies in skin and in brain.

A patient had the clinical and neuropathologic signs of Lafora's disease. Skin biopsy specimens from the midcalf area confirmed earlier findings by showing numerous periodic acid-Schiff-positive inclusion bodies in eccrine sweat gland duct cells. In our patient, however, inclusion bodies were more abundantly present in the apocrine sweat gland duct cells of the axilla skin. In brain biopsy specimens and autopsy material the same periodic acid-Schiff-positive inclusion bodies were found. From these data it can be stated that skin biopsy of the axilla is the method of first choice in confirming the diagnosis.

Completely thrombosed giant aneurysm of the basilar artery trunk: a case report.

A patient with a completely thrombosed giant aneurysm arising from the trunk of the basilar artery is described. Although it is difficult to differentiate this anomaly from a posterior fossa tumor, negative angiographic findings combined with certain computed tomographic (CT) signs may point to the correct diagnosis. Our case demonstrates that one of these CT signs (viz. ringlike contrast enhancement) can be explained by the presence of vasa vasorum in the aneurysm wall.

Subacute necrotizing encephalomyelopathy (Leigh syndrome) associated with disturbed oxidation of pyruvate, malate and 2-oxoglutarate in muscle and liver.

We studied a 17-year-old girl with subacute necrotizing encephalomyelopathy (Leigh syndrome). Lactate and pyruvate levels were increased in serum and cerebrospinal fluid. The oxidation rates of all substrates tested, i.e. pyruvate in liver, and pyruvate, malate and 2-oxoglutarate in muscle, were decreased, as was the production of adenosine triphosphate plus creatine phosphate. Cytochrome content was normal. The data imply a defect in oxidative phosphorylation, outside the cytochrome region.

Carcinoid of the larynx: a report of three cases and a review of the literature.

Carcinoid tumors are among the exceptional neoplasms of the larynx. The laryngeal carcinoid was first described in 1969 by Goldman, et al. Only 16 cases could be traced from the literature. This paper describes three additional cases. In one patient, the tumor infiltrated the laryngeal tissues and metastasized to the cervical lymph nodes breast. In the second case, the polypoid lesion could be excised completely. The third case was initially diagnosed as undifferentiated squamous cell carcinoma. The diagnosis of carcinoid was made a few years later when a metastasis was removed. The presence of intracellular membrane bound neurosecretory granules and positive argyrophilia in the Grimelius stain are characteristic. In half of the cases described in the literature, the tumor was initially misdiagnosed as undifferentiated carcinoma. The treatment of choice is surgical removal which may be curative. The literature is reviewed.

Computed tomography in the diagnosis of Wernicke's encephalopathy: a radiological-neuropathological correlation.

A case of Wernicke's encephalopathy with pathological verification is reported. Results of computed tomography scanning performed one day after admission of the patient, a male alcoholic, strongly suggested Wernicke's encephalopathy and were in agreement with the subsequent postmortem findings.

Defects in citric acid cycle and the electron transport chain in progressive poliodystrophy.

We will present 8 children with progressive infantile or juvenile poliodystrophy (Alpers' disease), associated with a defect in pyruvate metabolism. Laboratory studies showed elevated levels of lactate in CSF and, in 4 children, elevated levels in serum. Histopathologic studies revealed lipid storage in liver and/or muscle tissue, sometimes myopathy with abnormal mitochondria and slight axonal degeneration in the peripheral nerve. Autopsy showed the characteristics of progressive poliodystrophy with degeneration and loss of neurons. Electron microscopy of cerebral cortex showed no mitochondrial abnormalities in neurons or astroglia. Biochemical studies in muscle and/or liver and/or cerebral tissue showed different deficiencies in pyruvate metabolism: in the pyruvate dehydrogenase complex, in the second part of the citric acid cycle (after the oxoglutarate dehydrogenase complex), in the NADH oxidation, in cytochrome aa3 and in pyruvate carboxylase.

Malignant tumours of the nasopharynx: retrospective review of 74 cases.

Seventy-four patients with histologically confirmed malignant tumours of the nasopharynx were treated by the Departments of ENT and Radiotherapy of the Sint Radboud Academic Hospital, Nijmegen, The Netherlands. Selected prognostic factors were examined. The 5-year overall survival for the malignant epithelial tumours was 35%. The number of patients treated was too small to reach definite conclusions with respect to age and histology as prognostic factors. Staging, however, seems to be of value and it is suggested that the classification proposed in Kyoto, Japan, 1977 be adopted because it offers a better relationship between clinical staging and prognosis. From our data it appeared that treatment failure occurs mainly because of advanced initial tumour stage or distant metastasis; 40% of patients with initial locoregional control died because of distant metastasis. As half of the patients with distant metastasis presented with 'early' tumour stages (T1, T2, T3a), we strongly recommend adding systemic chemotherapy to the primary treatment of nasopharyngeal tumours.

Ultrasound detection of congenital arteriovenous aneurysm of the great cerebral vein of Galen.

Using combined echoencephalography and Doppler flow determination the diagnosis Arteriovenous aneurysm of the great cerebral vein of Galen could be made in two infants. Without vascular surgery one patient died, the other recovered completely. CT scanning confirmed the diagnosis. Invasive methods such as cerebral angiography were avoided. Case histories, neuropathological findings, ultrasound method and results are presented. Pathogenesis, clinical signs, treatment and prognosis are discussed. With the ultrasound method presented, the nature and location of the vascular anomaly were demonstrable, thus additional higher risk diagnostic methods could be avoided or planned more purposefully.

Progressive infantile poliodystrophy (Alpers' disease) with a defect in citric acid cycle activity in liver and fibroblasts.

We present the case history of a boy, who died at the age of 3 1/2 years after a rapidly progressive neurologic disorder, characterized by psychomotor retardation, hypotonia, hemiparesis, seizures and myoclonic contractions. Histopathologic studies showed slight lipid storage in liver. Autopsy showed the characteristic features of progressive infantile poliodystrophy (Alpers' disease); ultrastructural examination showed an increased density of mitochondria in cerebral gray matter. Biochemical studies in leukocytes, cultured fibroblasts and liver indicated a deficiency in the citric acid cycle between succinate and fumarate; this deficiency was not present in muscle tissue. This study supports the view that progressive infantile poliodystrophy is associated with abnormalities in pyruvate metabolism and/or in cell mitochondria.

Familial lissencephaly with extreme neopallial hypoplasia.

Two siblings, male and female, with identical lethal brain malformation are described. Their anomaly is characterized by very low brain weight, lissencephaly, wide ventricles and thin neopallium (colpocephaly) varying in thickness between 0.2 and 3 mm. The neocortex is four layered as in classic lissencephaly. Brainstem and cerebellar anomalies are more extensive than in cases hitherto described in detail. No extracranial malformation is found. The parental karyotypes are normal. The relationship to previously reported familial cases of lissencephaly and several inherited syndromes featuring lissencephaly is discussed. The present family may represent a severe expression of previously described autosomal recessive lissencephaly without extracranial anomaly or may represent a new genetic lissencephaly syndrome.