Terminals of intralaminar thalamic neurons in the pallidum externum of Saimiri sciureus.

Stereotactic coagulations of intralaminar thalamic nuclei in 6 squirrel monkeys Saimiri sciureus produced dark degenerations only of type IV synapses in pallidum externum, according to the classification of Hassler and Chung often preserving the slightly asymmetric contact and subsynaptic densities. Other type IV boutons underwent semidark degeneration, whereas others showed crystalloid degeneration. Some of type IV boutons show the deposition of many dense core vesicles and mitochondria with loss of most synaptic vesicles. Enlarged type IV boutons are sometimes overcrowded with irregularly shaped lysosomes. Thus, a monosynaptic connections of intralaminar thalamic nuclei to pallidum externum could be demonstrated.

Effect of motor and premotor cortex ablation on concentrations of amino acids, monoamines, and acetylcholine and on the ultrastructure in rat striatum. A confirmation of glutamate as the specific cortico-striatal transmitter.

At 1, 2, and 4 weeks after unilateral premotor and motor cortex ablation in rats, a significant and lasting decrease in glutamate levels in the ipsilateral versus contralateral striatum was observed. A significant corresponding fall in aspartate was seen only after 1 week. In contrast, there was a large increase in the striatal concentrations of lysine, threonine, alanine, and glutamine 1 week after the cortical ablation. This correlates with the extensive glial proliferation in the deafferented ipsilateral striatum. Four weeks after cortical ablation the GABA concentration was significantly increased. There was no decrease in other putative transmitters (dopamine, serotonin, acetylcholine, glycine and taurine), nor was a glutamate decrease observed in the hippocampus or in the hypothalamus, which do not receive direct premotor and motor cortical inputs. Both biochemical and morphological evidence for a minor contralateral cortico-striatal projection was obtained. Correlating with the fall in glutamate, ultrastructural observations indicated the degeneration of two types of striatal synapses, i.e., those of the axo-spinous type III and of the axo-dendritic type VII. Frontal cortex ablation clearly affects, in opposite directions, the metabolism of various striatal amino acids but not that of acetylcholine and the monoamine transmitters. The results strongly support the view that glutamate is the transmitter of the cortico-striatal fibers.

Degeneration of two of nine types of synapses in the putamen after center median coagulation in the cat.

The cat putamen contains the identical nine types of synapses and the same proportion of axo-dendritic (or axo-somatic) synapses as described for the fundus striati. However, type III (cortico-striatal) (31:16%) and type V Caxon-callateral) (13:1%) occur much more frequently and type I (nigro-striatal) much less frequently (14:34%) in the putamen than in the fundus striati. Of the axo-spinous synapses only type IV, with densely arranged small round vesicles and interrrupted, asymmetric contact, shows a dark degeneration after center median lesions, mainly in the parvocellular part. Of the six axo-dendritic (or axo-somatic) synapses, only type VII, with densely packed small round vesicles and asymmmetric contact, is degenerated after the same lesion in the center median nucleus. However, after such lesions type VII synapses are much more frequently degenerated in the putamen than those of type IV.

[Interaction between the systems involved in fast pain perception and in slow, persistent pain (author's transl)]. / 2. Wechselwirkungen zwischen dem System der schnellen Schmerzempfindung und dem des langsamen, nachhaltigen Schmerzgefühls

A single pinprick triggers both a pang, the "1st pain" and after a pause of 0.5 s, a spreading burning feeling, the "2nd pain". The 2nd pain is delayed because it is conducted by unmyelinated C-fibers at a rate of less than 1 m/s, 20 times slower than conduction of the 1st pain. In the spino-thalamic tract the myelinated fibers of the 1st pain conduct much faster than those of the 2nd pain, and terminate in the parvocellular ventroposterior (VP) thalamic nucleus, which projects to area 3b in the postcentral gyrus. The slow C-fibers of the 2nd pain terminate in cortex-independent thalamic nuclei like limitans, which project to the outer segment of the pallidum. This subcortical pain pathway is disinhibited after destruction of the cortical pathway of the 1st pain, so that the patients suffer from spontaneous agonizing pain feeling (thalamic pain). Unbearable pain in cases of thalamic softening, in anaesthesia dolorosa and in phantom pain can be relieved by stereotactic coagulation of the thalamic nuclei involved in the 2nd pain. Normally they are inhibited by the cortical pathway of the 1st pain.

Experimental kuru in the spider monkey. Histopathological and ultrastructural studies of the brain during early stages of incubation.

The brains of 10 spider monkeys inoculated intracerebrally with brain suspension from kuru patients have been studied histologically and ultrastructurally. The animals were killed by perfusion of fixative from four to forty-one weeks after inoculation, when healthy and free of neurological signs. Definite histopathological changes had occurred as early as four weeks after inoculation, when moderate numbers of bi-nucleated neurons were found within the limbic cortex, striatum, the hypothalamus and amongst the Purkinje cells of the cerebellum. At later stages of incubation a moderate loss of neurons in the cerebral and cerebellar cortex and a mild to moderate proliferation of fibrous astrocytes here and also in the hypothalamus were the most striking features. None of our cases showed either status spongiosus or the generalized astrocytic proliferation and hypertrophy, characteristic of fully developed experimental kuru, in any region of the brain. The principal ultrastructural abnormalities consisted of the formation of membrane-bound intracytoplasmic vacuoles, predominantly within dendrites, and of concentric laminar arrays derived from the endoplasmic reticulum. The former were seen in all regions of the brain examined and at all stages of incubation. Concentric laminar arrays were confined to the cerebellar nodulus, where they were most numerous in dendrites and neuronal perikarya four weeks after inoculation. Both changes are interpreted as an indication that the kuru agent acts upon the plasma membrane from an early stage onwards and, by stimulating its growth, leads to the formation of complex, membrane-bounded vacuoles and to hyperplasia of the endoplasmic reticulum. The formation of vacuoles is further regarded as the first sign of status spongiosus on an ultrastructural level. Attention is drawn to the great similarities between the changes observed in the present material and those described in the brains of patients dying from kuru and of primates with fully developed experimental kuru. The significance of the relatively rapid spread of the kuru agent throughout the brain is discussed in relation to the concept of "slow virus" diseases.

Intention myoclonus of multiple sclerosis, its patho-anatomical basis and its stereotactic relief.

The typical multiple sclerosis case considered here is especially informative from both the standpoint of its clinical course and on the basis of the autopsy findings. The foci responsible for the severe bilateral intention myoclonus of the trunk and limbs are the nerve cell losses in both red nuclei due to extensive and almost complete demyelination. Thereby the triangle of Mollaret between the red nucleus, inferior olives and dentate nucleus is involved as the patho-physiological circuit responsible for myoclonus. Stereotactic coagulation of dentato-thalamic fibres resulted in complete relief of intention myoclonus. With regard to the triggering of fresh demyelinating foci by stereotactic interventions, our point of view is as follows: Although a stereotactic operation introduces the possibility of triggering new demyelinating foci in less than 10% of the cases, such a possibility does not represent an absolute contra-indication to the stereotactic treatment of action myoclonus in multiple sclerosis, if the patient is informed accordingly.