«NOTES ON THE OLIVOCEREBELLAR CONNECTIONS* H. M. ZIMMERMAN AND BERNARD S. BRODY In a previous communication' evidence was adduced to indicate that the ...»
NOTES ON THE OLIVOCEREBELLAR CONNECTIONS*
H. M. ZIMMERMAN AND BERNARD S. BRODY
In a previous communication' evidence was adduced to indicate
that the dorsal accessory olives of the medulla are connected with
the dorsal part of the vermis (lingula, lobus centralis, culmen and
declive) and that the ventromedian accessory olives and the ventral
limbs of the inferior olives are connected with the ventral part of the vermis (folium, tuber, pyramis, uvula and nodulus). Holmes and Stewart2 and Brouwer3 previously had stated that there is a definite regional relationship between the different portions of the inferior olives and the different areas of the cortex of the cerebel- lum; that the dorsal olivary loops are connected with the dorsal cerebellar cortex, the ventral with the ventral part, the medial with the medial, and the lateral with the lateral part of the cortex.
Brouwer also quoted Bruns to the effect that the inferior olives send fibers to the uncrossed cerebellar cortex by way of the homolateral restiform body. These fibers were said to take origin from the dorsal portion of the olive.
These views on the olivocerebellar relationships are contradicted by the findings in the case reported by Spiller4, in which were present atrophy and sclerosis involving the vermis, lateral cerebellar lobes and inferior olives, but no changes in the accessory olives. Further doubt on the olivocerebellar connections was cast in a recent report by Pines and Surabaschwili5, who described an almost complete absence of the ventral part of the vermis in an individual who had, nevertheless, intact dorsal and median accessory olives.
Recently, the present writers had the opportunity to study the relationships between the olivary bodies and the various parts of the cerebellum in three cases which are presented in this communi- cation. This is done in the hope that some light will be thrown on what is still a controversial question.
REPORT OF CASESCase L.
Clinical History (No. 22382). Baby W., a white male infant, was born in the New Haven Hospital on February 5, 1932. The course of the preg- From the Department of Pathology, Yale University School of Medicine.
478 YALE JOURNAL OF BIOLOGY AND MEDICINEnancy and the delivery were normal in all respects. At birth the baby weighed 2514 gms., was quite feeble, and showed cyanosis of the hands and feet. The following congenital defects were noted: complete hairlip and cleft palate, an accessory digit arising from the proximal phalanx of the right thumb, and undescended testes.
Respirations were regular and slightly accelerated. From the first day of life the child began having frequent spells of cyanosis, usually after a feeding.
There was no evidence of congenital heart disease. Because the spells of cyanosis continued, some barium was introduced into the esophagus for the purpose of radiographic examination. By this means an atresia of the esophagus approximately 0.5 cm. above the bifurcation of the trachea was established. There were no abnormal changes found in either lung field by roentgenography. The child became weaker and extremely emaciated and died when two weeks old.
Necropsy. A wide cleft in the upper lip was present to the left of the midline and extending through the maxilla and roof of the mouth, exposing the turbinate bones. A small accessory digit, 1.1 cm. in length, was attached to the right thumb at the first phalanx. The ears were crumpled and lacked cartilage. Both testes were contained in the inguinal canals. The heart was slightly enlarged-the foramen ovale and ductus arteriosus were widely patent. Several small zones of atelectasis were noted in the apices of the upper lobes of both lungs.
The upper portion of the esophagus was markedly dilated, measuring, about 2 cm. in circumference. The dilatation ended blindly at the bifurcation of the trachea, at which point a small fistulous communication was found between the esophagus and trachea. A small diverticulum (Meckel) was seen in the small intestine about 30 cm. proximal to the ileocecal valve.
The bones of the cranium were over-riding and the fontanelles were depressed. The cerebral hemispheres were normal in size and symmetrically developed. There were no abnormalities in size of the cerebral convolutions.
The dorsal half of the vermis cerebelli was well formed, but the ventral half was underdeveloped and, as a result, the fourth ventricle was in direct communication by a large opening with the cisterna magna (Fig. 1). The aplasia of this part of the cerebellum involved the folium, tuber, pyramis, uvula and nodulus. Remnants of these structures were, however, present, as will be brought out more fully in the microscopic description. The flocculi and paraflocculi appeared to be fully developed.
Microscopic examination of the brain revealed a normal cerebral cytoarchitecture of six layers, but the central gray matter was composed of immature, small, round, indifferent cells. The cerebellum and medulla were sectioned serially at 20 microns; every tenth section was stained with toluidine blue (Nissl method) and mounted. The microscopic preparations thus obtained showed a normal architecture in the dorsal half of the vermis and in the lateral cerebellar lobes. The lingula, lobus centralis, culmen and W. I
FiC;. 2 (Case I). I"thotomicrograph of nodulus. Note thc aplasia and abnormal architecturc. Nissl; x25.
FIcG. 3 (Case I).-Photomicrograpli of roof of fourth ventricle showing malformation of nuclei fastigii. Nissl; x22.
declive were fully developed. On the ventral half of the vermis, the folium, tuber, pyramis, uvula and nodulus were all represented by small, aplastic and malformed structures. In these the architecture was disturbed by a disorderly arrangement of the granular and Purkinje cells (Fig. 2).
The nuclei fastigii in the roof of the fourth ventricle were almost entirely replaced by heterotopias of cerebellar cortex (Fig. 3), but a small number of nerve cells belonging to this nuclear mass were preserved. The nuclei globosi were sparsely populated with nerve cells, but otherwise were not abnormal.
There were no alterations in size or cellular content of the nuclei emboliformes and dentati.
In the serial preparations of the medulla it was found that the dorsal accessory olives were bilaterally well preserved, of normal size, and normally situated. But this was not so with the ventral accessory olives. In most of the preparations there were no ventral accessory olives-only in those preparations at levels through the posterior parts of the main inferior olives did groups of cells come into view in positions ventro-medially to the main olives.
These represented attenuated ventral accessory olives, but in a few of the preparations they did take on their normal magnitude. However, in these very sections it could be observed that the ventro-median limbs of the inferior olives were strikingly wanting in cells (Fig. 4).
The subject of this study, a white male infant two weeks old, presented a variety of congenital defects of which the complete hairlip, cleft palate and esophageal atresia were directly responsible for his death. There was also present an aplasia of the ventral part of the vermis cerebelli, which was associated with a malformation and underdevelopment of the nuclei fastigii and globosi. Dependent on this anomalous condition of the cerebellum was a striking aplasia of ventral accessory olives and of the median parts of the inferior limbs of the main olives in their caudal extremities.
Clinical History (No. A809). D. C., a white female 23 years of age, was admitted March 13, 1931, to the New Haven Hospital with a history of frequent attacks of dizziness, vomiting and headache of six years' duration.
The vomiting usually occurred soon after meals and seemed to relieve the headache and dizziness. In December, 1930, the patient contracted an infection of the upper respiratory tract, and during the course of a routine physical examination, she was found to have a blood-pressure of "over 200", albuminuria, and pufliness of the face and ankles.
480 YALE JOURNAL OF BIOLOGY AND MEDICINEOn admission to the hospital the heart was found to be moderately enlarged to the left. A soft systolic and a presystolic murmur were heard at the apex.
Blood studies revealed a secondary anemia, an N. P. N. of 96 mg., and negative serology. The urine showed a low specific gravity and traces of albumin. The excretion of phenolsulphonphthalein in two hours was only 11 o. There was blurring of the optic nerve heads, but the discs were not elevated. The retinal arteries were narrowed and the veins were tortuous.
A diagnosis was made of rheumatic heart disease with mitral stenosis and chronic glomerular nephritis. Following a slight improvement in her condition the patient was discharged from the hospital on April 30, 1931.
On May 20, 1931, she was readmitted with the complaint of frequent frontal headache and pain in the back, knees and ankles. She became drowsy, vomited frequently, and had three generalized convulsions on the sixth day after admission. A striking remission in symptoms occurred, however, and she was able to leave the hospital June 27, 1931, feeling somewhat improved.
Headache, vomiting and blurring of vision forced her to reenter the hospital for the third time on October 16, 1931. These symptoms continued, drowsiness made its appearance, and uremic twitchings developed. Finally, signs of pericarditis, intraventricular heart block and heart failure appeared.
The patient lapsed into deep stupor and expired January 20, 1932.
Necropsy. Extensive pitting edema was present over the lower extremities and extended up over the thighs, sacrum and entire back. The peritoneal cavity contained 500 cc. of clear, pale yellow fluid. The lower margin of the liver extended down to the level of the umbilicus. About 1000 cc. of straw-colored fluid were present in each pleural cavity, and 100 cc. of similar fluid containing fibrin were found in the pericardial sac. The mitral valve was slightly thickened; the heart was hypertrophied and dilated. A chronic urethritis resulting in stricture of the urethra and a chronic cystitis were present. The urinary bladder was hypertrophied and there were present bilateral hydro-ureters and hydronephrosis. In addition to these changes in the kidneys, these organs were also scarred, and on histologic examination showed glomerular adhesions and hypertrophy and dilatation of tubules.
The brain was small but symmetrically developed. The cortical gray matter of the cerebrum was of uniform width and color and could easily be defined from the subcortical white matter. The dorsal half of the vermis cerebelli was replaced by a cyst measuring 2.5 cm. in width and 3.5 cm. in length (Fig. 5). The lingula, however, was left intact, the lesion involving the lobus centralis, culmen and declive. The cyst destroyed the folium and tuber of the ventral half of the vermis, but the other parts of this half of the vermis were quite normally preserved. The roof of the cyst was composed of thickened pia-arachnoid and the remaining walls were formed of the adjoining cerebellum. These walls were smooth and stained with old blood pigment. There were no alterations to be noted in the cortex of the lateral LI NGULA
FIG. 5 (Case II).-Drawing of brain-stem and cerebellum showing cyst in vcrmis.
Fic. 6 (Case 1I).-Photomicrograph of left side of medulla. Note paucity of cells in dorsal and ventromedian accessory olives.
D. A. O.-dorsal accessory olive; V. A. O.-ventromedian accessory olive.
L FIG. 7 (Case ILL).-Drawing of cerebellum showing destruction of left lobe by cystic astrocytoma.
lobes of the cerebellum or in the dentate nuclei. Macroscopic examination of the medulla revealed no changes.
Microscopically there were found no changes of a vascular nature in either the pia or cerebral parenchyma except for a single small perivascular zone of softening in the subcortex of the parietal lobe. The wall of the cyst in the dorsal part of the vermis was composed of glia cells and their processes. A few of these cells were found containing old blood pigment. From these findings it is apparent that the cyst was the result of a degenerative process of vascular origin and that it was of long standing. Furthermore, it was sharply limited to the structures in the cerebellum previously enumerated.
The cortex of the lateral lobes of the cerebellum presented a normal histologic picture and the nuclei dentati and emboliformes were well preserved. The vermis was sectioned in a sagittal plane and therefore the nuclei fastigii and globosi were not incorporated in the microscopic preparations.
In the preparations of the medulla it was seen that the dorsal accessory olives bilaterally were almost completely devoid of nerve cells-an average of eight of these cells were all that remained in each dorsal accessory olive in each microscopic preparation (Fig. 6). These intact cells are probably to be linked to the intact lingula. In the more rostral part of the inferior olives there was also a paucity of nerve cells in the median accessory olives, where an average of twelve such cells remained. More caudally, however, the median olives had their normal complement of nerve cells. The viable cells were probably linked to the intact nodule, uvula and pyramis, whereas those that degenerated and disappeared were probably linked to the destroyed tuber and folium belonging to the ventral half of the vermis. The median parts of the inferior limbs of the main olives and, indeed, the remainder of the inferior olives were quite intact.
This patient, a white female 23 years of age, had symptoms of chronic nephritis associated with hypertensive heart disease of about six years' duration. In addition to the anatomic evidence of chronic nephritis and cardiac hypertrophy and dilatation, there was found at necropsy a degenerative cyst in the vermis cerebelli which destroyed the lobus centralis, culmen, declive, folium and tuber.