Arnulf H. Koeppen

Central nervous system vasculitis in cytomegalovirus infection

A 51-year-old man received cyclophosphamide, vincristine, procarbazine and prednisone in the treatment of a small-cell undifferentiated lymphoma. Two years later, he developed a rapidly progressive neurological syndrome characterized by a decline in alertness, deafness, blindness and paraplegia. Examination of his eyes revealed severe hemorrhagic chorioretinitis. Leg weakness was thought to be due to transverse myelopathy at a thoracic level. He had a grand mal convulsion and died from terminal bronchopneumonia. Autopsy examination of the eyes revealed sweeping destruction of the retina due to inclusion body chorioretinitis. The brain and spinal cord showed multiple small infarcts accounting for the deafness and paraplegia. The lesions were due to occlusive arteritis in gray and white matter. Veins were also involved. Tissue surrounding the foci of necrosis contained cells with intranuclear an intracytoplasmic inclusion bodies. Some of the Cowdry type A inclusion bodies were large, measuring 30 micrometer in diameter and were located in enlarged cells. Electron microscopy of retina and brain tissue disclosed virus particles compatible with cytomegalovirus. The subject of cerebral and ocular angiitis due to herpes virus infections is reviewed.

Supranuclear ophthalmoplegia in olivopontocerebellar degeneration.

Autosomal dominant olivopontocerebellar degeneration was diagnosed in a family of Scottish ancestry by clinical examination and autopsy. In addition to having progressive cerebellar ataxia, head titubation, and severe dysarthria, the patients are unable to initiate saccadic eye movements. Slow pursuit movements are normal. Reflex movements of the eyes caused by passive rotation or caloric labyrinthine stimulation are not impaired but are not associated with nystagmus. The phenomenon can be classified as supranuclear pseudo-ophthalmoplegia. It differs from congenital ocular motor apraxia in age at onset and the absence of random eye movements. The anatomic lesion responsible for the defect of saccadic eye movements remains to be established.

The nucleus pontis centralis caudalis in Huntington's disease*

Slow saccadic eye movements occur in some patients with Huntingtons disease (HD), and minor defects of supranuclear eye movement control can be demonstrated in the majority by neuroophthalmological laboratory methods. In the pathogenesis of slowed saccades, a lesion of the paramedian pontine reticular formation and specifically the nucleus pontis centralis caudalis was considered likely due to similar eye movement disturbances in well documented degenerative and vascular lesions of the lower pontine tegmentum. A systematic morphometric study was performed on the nucleus pontis centralis caudalis in 9 patients with HD. Two of them had grossly defective saccades during life, and 7 had normal eye movements on routine examination. In 8 patients, the nucleus was reduced in size, revealed a higher than normal neuronal density, and a striking loss of large neurons. One patient with HD and normal morphometric results had died 2 years after the onset of chorea from an unrelated illness. It is proposed that the nucleus pontis centralis caudalis is regularly affected in HD and that progressive loss of large neurons is the cause of saccadic slowing.

Foix-Alajouanine Syndrome*

SummaryTwo patients with progressive flaccid and areflexic paraparesis were found, at post mortem examination, to have the Foix-Alajouanine syndrome. The thoracic spinal cord was surrounded by dilated, tortuous and thick-walled venous channels embedded in fibrotic arachnoid. The spinal cord at the midthoracic level and below was severely necrotic. Intramedullary blood vessels frequently showed fibrinoid necrosis and there was proliferation of blood vessels within necrotic parenchyma. Histochemical methods and scanning electron microscopy identified an excess of calcium in the wall of proliferated intramedullary blood vessels and abnormal distribution of phosphorus and sulfur. The etiology of the Foix-Alajouanine syndrome remains unknown but the lesions are probably acquired.

The origin of free brain malonate

Rat brain contains substantial concentrations of free malonate (192 nmol/g wet weight) but origin and biological importance of the dicarboxylic acid are poorly understood. A dietary source has been excluded. A recently described malonyl-CoA decarboxylase deficiency is associated with malonic aciduria and clinical manifestations, including mental retardation. In an effort to study the metabolic origin of free malonate, several labeled acetyl-CoA precursors were administered by intracerebral injection. [2-14C]pyruvate or [1,5-14C]citrate produced radioactive glutamate but failed to label malonate. In contrast, [1-14C]acetate, [2-14C]acetate, and [1-14C]butyrate were converted to labeled glutamateand malonate after the same route of administration. The intracerebral injection of [1-14C]-β-alanine as a precursor of malonic semialdehyde and possibly free malonate did not give rise to radioactivity in the dicarboxylate. The labeling pattern of malonic acid is compatible with the reaction sequence: acetyl-CoA→malonyl-CoA→malonate. The final step is thought to occur by transfer of the CoA-group from malonyl-CoA to succinate and/or acetoacetate. Labeling of malonate from acetate is most effective at the age of 7 days when the net concentration of the dicarboxylic acid in rat brain is still very low. At this age, butyrate was a better precursor of malonate than acetate. It is proposed that fatty acid oxidation provides the acetyl-CoA which functions as the precursor of free brain malonate. Compartmentation of malonate biosynthesis is likely because the acetyl-CoA precursors citrate and pyruvate are ineffective.

POLYMYOSITIS IN KAPOSI SYNDROME

Polymyositis in association with Kaposi sarcoma occurred in a 60-year-old black man. Muscle biopsy revealed prominent plasmacytic and eosinophic inflammatory infiltration resembling the myopathy of Sjögrens syndrome. Nonspecific changes were seen by electron microscopy of post mortem muscle. The myopathy could be interpreted as a remote effect of neoplasm.

Growth Studies on Fibroblasts of Patients with Autosomal Recessive Friedreich’s Ataxia

Fibroblasts derived from patients with undisputed autosomal recessive Friedreichs ataxia were examined for their growth characteristics including plating efficiency, proliferation curves and cumulative number of population doublings. In comparison to cells of healthy controls, the cells from ataxia patients showed lower plating efficiency, growth rate and number of cumulative population doublings in these parameters. Cells of heterozygotes showed clonal growth and growth curves in the range of the healthy controls.