Otto Appenzeller

HEADACHE IN SMALL VESSEL DISEASE OF THE BRAIN: A STUDY OF PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

SYNOPSIS

FLASH EVOKED POTENTIALS IN MIGRAINE

A VOLLEY of nerve impulses occurs in response to light falling on the retina. These are transmitted through the optic nerve tract and radiation to the occipital cortex. This electrical response can be recorded through scalp electrodes using appropriate averaging techniques. The latency and wave forms of the potential evoked by bright flashes varies somewhat amongst individuals; nevertheless, in patients having lateralized visual deficits simultaneously recorded interhemispheric differences in the visual evoked responses might be of interest.

Macrodactyly and localized hypertrophic neuropathy

A case of focal hypertrophic neuropathy involving the left median nerve associated with macrodactyly of the left thumb is reported. The pathologic picture showed classic onion bulb formation caused by proliferation of Schwann cell processes, collagen, and fibroblasts. An unusual feature of the ultrastructural aspects of the disorder, to our knowledge not previously recognized, was the participation of processes from one Schwann cell in the formation of several onion bulbs. Although the relationship of the focal hypertrophic neuropathy to the macrodactyly remains speculative, it is tentatively attributed to disturbed trophic functions of peripheral nerves. Onion bulb formation, although not usually clinically apparent at birth, might arise in utero, since the macrodactyly in our patient was noted in infancy.

Pathogenesis of vascular headache of the migrainous type: the role of impaired central inhibition.

5-HT HAS BEEN demonstrated in brain.1 The functional role of 5-HT in the central nervous system is not entirely clear, but abnormalities of brain 5-HT metabolism have been postulated in some neurologic disorders. 5-HT levels are decreased in the brain of patients with Parkinsons disease but the administration of a 5-HT precursor L-5-hydroxytryptophan (L-5HTP) to patients with Parkinsonism does not improve their clinical state. Defects in brain 5-HT metabolism have also been postulated in Huntingtons chorea and Downs syndrome and in these disorders the administration of L-5HTP is also ineffective.2,3 L-5HTP, improves however post-anoxic myoclonic jerks.4 In animals the injection of L-5HTP has produced brief repetitive movements reminiscent of myoclonus. L-5HTP has been found effective recently in the treatment of intention myoclonus resulting from cerebral anoxia when given with a decarboxylase inhibitor.5 In patients with intention myoclonus the concentration of CSF 5-hydroxyindoleacetic acid (5-HIAA) a metabolite of 5-HT was found to be low and this was increased by the administration of L-5HTP. This increase in CSF 5-HIAA concentration coincided with marked clinical improvement. These observations suggest that in post-anoxic intention myoclonus, there might be a deficiency of brain 5-HT. It has been proposed that myoclonus is a release phenomenon which arises from an irritable focus of discharge because of removal of higher center control.6 The therapeutic effect of the postulated elevation of brain 5-HT by L-5HTP in patients with intention myoclonus has been attributed to a suggested central inhibitory synaptic neurotransmitter activity of 5-HT. The absence of central inhibition due to impaired 5-HT function causes intention myoclonus in response to lesions of the central nervous system.

VASOMOTOR FUNCTION IN MIGRAINE

MANY SYMPTOMS and signs of migraine have been attributed to changes in the caliber of cerebral vessels.1 The reason for these changes remains, however, obscure. Because cerebral vessels are not normally available for study, other vascular beds have been examined in migraineurs and a number of abnormalities have been found in such patients during headache-free intervals. For example, in women the subsequent occurrence of headaches could be predicted before the administration of oral contraceptives from the appearance of endometrial arterioles in biopsy specimens.2 In headache-susceptible women, abnormal groups of arterioles during the early part of the cycle were seen but these were not found in controls. Anatomical differences in the capillary pattern of the fingernail folds have been described also,3 and a reduction in size and in the amplitude of pulsations of extracranial vessels has been found.4,5

Sea-blue histiocytes and sural nerve in neurovisceral storage disorder with vertical ophthalmoplegia

Ultrastructural investigation of bone marrow histiocytes in neurovisceral storage disorder associated with vertical ophthalmoplegia revealed 3 types of cytosomes: (1) lamellar cytosomes; (2) larger cytosomes composed of lamellar fragments and a granular component; and (3) large irregular cytosomes with amorphous and granular portions, often including fingerprint profiles--in some of these, lysosome-like bodies were numerous. The lamellar cytosomes corresponded to vacuoles seen by light microscopy. The Type 2 and 3 cytosomes were the ultrastructural substract of Wright-Giemsa stained blue granules. Histiocytes having a predominance of Type 2 cytosomes in a cytoplasm rich in free ribosomes had the appearance of sea-blue histiocytes at the light-microscopic level. Transformed Type 1 cytostomes served as building blocks for Type 2 and 3 cytosomes. In the sural nerve, Schwann cells and endoneurial fibroblasts accumulated autofluorescent lipopigment but no lamellar cytosomes or their fragments were found on electron-microscopic examination. Ultrastructure of sea-blue histiocytes in this disease differed from that observed in some other diseases.

Myelinated fibres in the human paravertebral sympathetic chain; quantitative studies on white rami communicantes

Myelinated fibres in the human sympathetic paravertebral chain were examined histologically and in single teased fibre preparations in various age groups in subjects dying from disorders not affecting primarily the autonomic nervous system. An increase in fibre density predominantly due to an increase in the number of small fibres was found in older subjects. A correlation between internodal length and fibre diameter was found but the internodes of sympathetic myelinated fibres are shorter for any given diameter than those found on fibres of comparable size in the sural nerve. A reduction in internodal lengths with advancing years was demonstrated. These observations are interpreted to show that Wallerian degeneration and segmental demyelination occur with increasing frequency in old age and that regeneration does not keep pace with successive degenerative events. The deterioration in function of the autonomic nervous system with advancing years may be attributed in part to the changes found in myelinated fibres in the paravertebral sympathetic chain.

Neurofibromatosis xenografts. Contribution to pathogenesis

We transplanted Schwann cells of 3 patients with neurofibromatosis from neurofibromas, sural nerve, and from a malignant schwannoma into sciatic nerves of immunoincompetent mice. Three and six months later, the grafts and distal nerve segments contained normal myelinated fibers. After rendering host animals immune competent again, neurofibroma and malignant schwannoma Schwann cells were rejected, but grafts retained normally myelinated fibers indicating that these were of mouse origin. Sural nerve Schwann cells from a neurofibromatosis patient were rejected also leaving naked axons in the grafted segments showing that human Schwann cells from the sural nerve of one patient had invested and myelinated the regenerating mouse axons. The nature of putative signals passing between axons and Schwann cells might be elucidated by the combination of human and animal cells in immunoincompetent host nerves. Hypothetical signals for myelination of mouse axons were normally received by sural nerve Schwann cells of a patient with neurofibromatosis, but not by Schwann cells from neurofibromas or malignant schwannomas.

HEMICRANIA AND RAYNAUD'S PHENOMENON — MANIFESTATIONS OF THE SAME DISEASE?

Dr. Atk.: A 36 year old, married, housewife has recurrent, throbbing headaches involving the right side of the head, rarely, the left, for the past 17 years. At the onset, the pain may be associated with dizziness and blurred vision. Nausea is frequently present during an attack. Her husband has noted drooping of the right eyelid and outward pointing of the right eye during headache. In the past the headaches have been associated with menstrual periods, but recently they occur almost daily. She has noted that the pain may be brought on by alcohol, but other dietary factors have not induced attacks.

Autonomic failure in hydrencephaly

Autonomic functions were studied in three patients with hydrencephalus and five with hydrocephalus. Autonomic failure of central origin was found in the patients with hydrencephalus; whereas, those suffering from hydrocephalus had essentially normal autonomic function. In two patients with hydrencephalus, the hypothalamus was markedly abnormal but the rest of the autonomic nervous system was histologically normal. From this it is concluded that in some patients with mental and motor retardation, autonomic failure may be of cerebral origin but that this is not a feature of patients with hydrocephalus.