David H. George

Clinical-pathological study of levodopa complications.

We sought to determine the continued benefit and the pattern of motor complications of long‐term levodopa treatment in Parkinsons disease. Patients were evaluated between 1968 and 1996. Only those who had an adequate levodopa trial and in whom autopsy revealed Lewy body Parkinsons disease were included. Total levodopa and mean daily dose were calculated in each case. Dyskinesia, wearing‐off and on‐off were collectively classified as motor adverse effects and reported as cumulative incidence. Forty‐two patients (male, 30; female, 12) with mean 15.9 years of illness and 9.1 years follow‐up received on average 500‐mg levodopa daily over 9.8 years. Seventeen of 21 patients assessed during the last 18 months of life reported some motor benefit. Adverse effects were seen in 71.4% of patients. The most common was dyskinesia, in 61.9%; wearing‐off in 35.7%; and on‐off in 16.7% of patients. The earliest adverse effect was dyskinesia and the last to emerge was on‐off. Isolated dyskinesia was seen in 35.7% and wearing‐off in 7.1% of patients; 15.5% of patients developed dyskinesia after 2.6 years and 31% after 6.4 years on levodopa. We concluded that levodopa benefit declined and adverse effects increased with time. Dyskinesia was the earliest and the most common isolated adverse effect.

SMI-32 immunoreactivity in human striate cortex during postnatal development

SMI-32, an antibody which recognizes the non-phosphorylated epitopes on the neurofilament proteins was used to study the morphological changes in the human striate cortex during postnatal development. Striate cortices from 12 autopsied patients with ages ranging from 1 day to 70 years were obtained. Using the avidin-biotin-peroxidase method, the first SMI-32 immunoreactive neurons were identified at sublayers Vb/VIa on the first postnatal day. At 5 months, the next group of neurons to develop immunoreactivity were in IVb. By 15 months, SMI-32 immunoreactive neurons were observed at III, IVa, IVb, V and VI. The changes in SMI-32 immunoreactivity (ir) were stabilized from 3 years and after. The SMI-32 ir in the striate cortex could be a useful morphological correlate for studying developmental diseases affecting the neocortex.

Ultrastructural morphology and cellular differentiation in acinic cell carcinoma

Acinic cell carcinomas, in some instances, contain a component of intercalated duct cells. However, the manner in which this element is integrated within the more obvious acinar cells, as well as the role neoplastic intercalated duct cells play in determining morphologic patterns in acinic cell tumors, has not been fully investigated. Ultrastructural study and immunostaining with antibodies to cytokeratins and to S-100 protein carried out in nine cases of parotid acinic cell carcinoma suggest two basic differentiation patterns. In three cases, the lesions were essentially composed of acinar cells (with variation in the number and form of secretory granules), and one of these tumors was unique in having ultrastructural evidence of differentiated myoepithelial cells. In the second group of six cases, there was light microscopic, ultrastructural, and immunohistochemical evidence of a significant component of intercalated duct cells. By means of both immunostaining (intercalated ducts were positive for keratin and S-100 protein; acinar cells were negative for both antigens) and electron microscopy, flattened-to-cuboidal intercalated duct cells were noted to enclose and, presumably, to be involved in the formation of microcystic spaces. Acinic cell carcinomas with a more solid growth pattern contained groups of intercalated duct cells positive for keratin and S-100 protein. Ultrastructurally, these cells were organized into well-formed ducts related to nests of acinar cells. Acinic cell carcinoma is another class of salivary gland tumor in which there can be an integrated proliferation of intercalated duct and acinar cells and, infrequently, of myoepithelial cells, all organized in a simulation of the intercalated duct-acinar unit of the normal salivary gland.

Association of infantile neuroaxonal dystrophy and osteopetrosis: a rare autosomal recessive disorder

The association of neuroaxonal dystrophy and osteopetrosis is reported in 2 siblings born to non-consanguineous parents. The 1st child was diagnosed as having infantile osteopetrosis shortly after delivery. A computed tomography scan of the head revealed agenesis of the corpus callosum. She died at the age of 9 months. Post-mortem examination showed pneumonia and bony sclerosis. Neuropathological examination revealed cerebral atrophy, ventricular dilation, absence of the corpus callosum, and a small hippocampus. Neuroaxonal spheroids were found in hippocampus, basal ganglia, pons, medulla, spinal cord, cranial nerves, cerebellum, and peripheral nerves. Ultrastructural examination revealed membranous cytoplasmic bodies and electron-dense granular deposits within the neuroaxonal spheroids as well as the soma of neurons. The 2nd child was delivered at 36 weeks of gestation because of intrauterine fetal distress. The diagnosis of osteopetrosis and partial agenesis of the corpus callosum was made shortly after delivery. The child died at 1 month without an autopsy. There are rare cases reported previously with the association of neuroaxonal dystrophy and osteopetrosis. We review these cases and compare them with ours.

Increase in enkephalin-like immunoreactivity in hippocampi of adults with generalized epilepsy

The changes of opioid peptide reactivity in seizure activity have been well studied in animals. Increased enkephalin and dynorphin immunoreactivity in the hippocampi of animals are interpreted as the result of seizure induced mossy fibre sprouting. We studied the hippocampi of six patients with a history of long-standing grand mal seizures and six age-matched control patients with no history of epilepsy or neurologic disease, using frozen sections which were immunostained with antibodies against Leu-enkephalin and Met-enkephalin. The staining intensity in the CA3, CA4 and internal molecular layer of the dentate fascia in each case was quantified using optical densitometry image analysis. The CA3 and CA4 of the epileptic hippocampi showed highly significant increase in Leu-enkephalin-like immunoreactivity compared to the controls (P < 0.005) while the inner molecular layer showed only significant increase (P < 0.05). Met-Enkephalin-like immunoreactivity was only significantly increased in CA4 of the epileptic hippocampi (P < 0.05).

Cerebral malignant tumors with ependymal and choroidal differentiation in two siblings.

&NA; Two siblings in a family without a history of phacomatosis or cerebral tumors developed malignant tumors in the posterior fossa at age 28 months and in the left cerebral hemisphere at age 15 months, respectively. Dual ependymal and choroid plexus epithelium differentiation was established by histological, ultrastructural, and immunocytochemical studies. The development of this rare tumor in siblings suggests an inherited predisposition, a common environmental insult, or both.

Dense microspheres in the human hippocampus.

SummaryDense microspheres (DMS) are structures found within neuronal processes of the adult human brain. Although best known as a feature of the neocortex, they are also found in the hippocampal formation. We describe a characteristic pattern of DMS distribution in the human hippocampus. The functional significance of this pattern is unknown, but it casts doubt on the proposed relationship of DMS to senile plaques. We also present evidence that DMS are composed of protein, but without a significant component of carbohydrate or neutral glycoprotein.

Delayed changes of chromogranin A immunoreactivity (CgA ir) in human striate cortex during postnatal development

The changes in chromogranin A expression in the human striate cortex from birth till 67 years were studied by immunohistochemical method in 18 autopsied patients. The first chromogranin A immunoreactivity (CgA ir) was identified at birth in layer IV (especially IVc) mainly as fine nerve terminals. By 6 months, the first perikaryal reactivity was noted in the large pyramidal neurons of layer V. The smaller neurons in layers IV, V and VI showed a progressive increase in CgA ir from 15 months to about 17 years. At approximately 9 years, immunoreactivity began to be noted in supragranular neurons in layers II and III. The final laminar distribution of CgA ir seemed to be attained at about 25 years with relatively little change thereafter. The CgA ir in the striate cortex demonstrates a prolonged period of developmental changes, lasting from birth to about 25 years.