REPRINTED EROM UNIVERSITY Medical Magazine. COITEO UNDER THE AUSPICES OF THE ALUMNI AND FACULTY OF MEDICINE OF THE UNIVERSITY OF PENNSYLVANIA. EDITORIAL STAFF Editci.al Committee: CONTENTS. yuicu aaLOo a. xxt JUNE, 1894 A CONTRIBUTION TO THE PATHOLOGY OF FRIEDREICH'S ATAXIA. BY CHARLES W. BURR, M.D. A CONTRIBUTION TO THE PATHOLOGY OF FRIED- REICH'S ATAXIA.1 By Charles W. Burr, M.D. The specimens I present are from Sadie T., who was exhibited in life by Dr. J. P. Crozer Griffith at the meeting of the Philadelphia College of Physicians in February, 1888. I quote the history in brief.2 The family history is negative, except that one brother suffers from the same disease. The patient was well until the tenth year, when she began to be nervous. Her hands shook while eating, and her gait was somewhat staggering. Following typhoid fever the nervousness in- creased, and she was unable to walk without crutches. At this time the arms were but little affected. There were subjective sensations of heat in the feet and aching in the legs, but no fulgerant pains. There were no apparent objective sensory changes in the legs. She ap- plied for treatment at the Infirmary for Nervous Diseases when six- teen years old, and the following notes were made: "Sensation per- fect. No tendon reflex. She can make all movements of arms and legs, but is utterly unable to stand. Choreiform movements occur in the hands." She entered the Home for Incurables, December 20, 1880. There was then marked incoordination and affection of speech. Present Condition.-August 16, 1887. Intelligence good; cannot sit erect; right dorsal scoliosis ; slight talipes equino-valgus ; no more atrophy than would follow from disuse; patellar reflex abolished ; power in arms good. In grasping an object the fingers and hand are extended over it like a claw ; no motion or tremor of the hands when in repose, but on voluntary effort slow ataxic movements of the fingers develop, somewhat resembling athetosis; marked incoordination on picking up a pin ; she cannot cut her food, but can feed herself; she can scarcely touch the tip of her nose with the fingers, whether the 1 The substance of a communication to the meeting of March, 1894, of the Philadelphia Patho- logical Society, March 8, 1894. 2 Transactions of the College of Physicians of Philadelphia, February 1, 1888. 2 Charles W. Burr. eyes are open or shut; the handwriting is almost illegible ; there are at times irregular, lateral, oscillatory movements of the head ; speech is peculiar,-jerking, but not scanning ; pupillary reflexes are normal; very slight and inconstant nystagmus on extreme lateral movement of the eyes ; fundus, examined by Dr. Charles S. Turnbull, normal; urine alkaline, albuminous, and contains numerous leucocytes ; there is prob- ably slight retardation of sensation. Such was the patient's condition at the time of Dr. Griffith's report. Several years later she came under my care at the Home. All symp- toms had increased in severity, and general paralytic weakness had Fig. i. Friedreich's ataxia. Upper cervical region. Sclerosis of the posterior columns, the crossed pyramidal tracts, the direct cerebellar tracts, and the direct pyramidal tracts. been added to the ataxia. She developed phthisis and glycosuria, and retardation of sensation became very marked. There was never anes- thesia to deep pressure, but a light touch on the hands and feet was often not felt. She died September 2, 1892. The post-mortem revealed tuberculosis of the right apex, and a tuberculous abscess of the right kidney. Otherwise the abdominal and thoracic viscera were normal. Skull normal. Meninges of the brain and cord normal. The cerebrum, cerebellum, pons, and medulla were slightly smaller than normal, not sufficiently so to be called atrophic, but simply a little below the aver- age. The circumstances of the autopsy prevented weighing. The spinal cord was very small in both the antero-posterior and lateral diam- eters, especially in the cervical and lumbar swellings. Its length was normal. Consistency harder than usual. The brain and cord were hardened in Muller's fluid, and sections stained with carminate of soda, aniline blue-black, and by Weigert's Pathology of Friedreich's Ataxia. 3 method. Microscopic examination of the cerebrum, cerebellum, pons, and medulla revealed nothing abnormal. Upper Cervical Region.-(Fig. 1.) Goll's columns are completely sclerosed, except a small area directly in contact with the posterior commissure in which are found quite a number of healthy fibres. There is marked, but not complete, sclerosis of Burdach's columns, there being many healthy nerve fibres scattered. here and there along the internal edge of the posterior commissure and horn. The lateral pyr- amidal tracts are almost entirely, and the direct cerebellar markedly, sclerosed. The direct pyramidal tracts are entirely sclerosed, the con- dition extending a little way round the periphery. Cervical Swelling.-(Fig. 2.) Complete sclerosis of Goll's col- Fig. 2. Friedreich's ataxia. Cervical swelling. Sclerosis of the posterior columns, direct and crossed pyramidal tracts, and direct cerebellar tract. umns, and almost complete of Burdach's, there being, however, a thin strip of almost normal tissue along the edge of the posterior com- missure and horns. Sclerosis of the direct and crossed pyramidal and direct cerebellar tracts. Upper Dorsal Region.-(Fig. 3.) The same as above, except that the area of sclerosis along the edge of the anterior longitudinal fissure is less in extent. Lower Dorsal Region.-Posterior columns as above. Sclerosis of the crossed pyramidal tracts. No sclerosis along the borders of the anterior longitudinal fissure. Lumbar Swelling.-(Fig. 4.) Complete sclerosis of the posterior columns. Sclerosis of the lateral columns extending outwardly to the periphery, and inwardly to the external edge of the posterior horns. Lower Lumbar Region. - Slight sclerosis of the posterior col- umns. 4 Charles W- Burr. The lesion of the lateral columns is not strictly confined through- out the cord to definite tracts, but varies in extent at different levels, and is diffuse rather than systematic. There is not the clean-cut boundary between healthy and diseased tissue which we find, for in- stance, in the descending degeneration following a cerebral lesion. The Fig. 3. Friedreich's ataxia. Upper dorsal region. Scle- rosis of posterior columns, and direct and crossed pyramidal tracts. lesion in the direct pyramidal tract is clean-cut and definitely bounded. Throughout the entire length of the cord there is more or less degen- eration of the posterior nerve-roots, none of the anterior roots. The cells of the anterior horns are with few exceptions normal, here and Fig. 4. Friedreich's ataxia. Sclerosis of the posterior columns and crossed pyramidal tracts. there we find one shrunken and without processes. The posterior horns are in many places not clearly distinguishable from the neighboring white matter, and the cells are degenerated. The cells of Clarke's Pathology of Friedreich's Ataxia. 5 column are markedly degenerated. The central canal is for the most part blocked by deeply-staining nuclear masses. On microscopical examination of the affected tissue we find the connective tissue septa from the pia indistinguishable in the areas of greatest disease. There is no increase in the number of blood-vessels, and but little, if any, thickening of the walls of those present. In some, however, the walls are apparently hyaline. The sclerosis is made up of a very fine fibrous material, with some proliferation of nuclei. It stains intensely with carminate of soda and aniline blue-black. All attempts to differentiate the connective tissue from the neuroglia by Malassez's method failed miserably. I am unwilling to say that this may not have been due to my lack of skill in the technique of the method. Two views are held as to the seat of the gross primary lesion of this affection. The first, and this is the more prevalent opinion, is that it is a disease of the spinal cord. The second, that it is cerebellar in origin, was first promulgated many years ago by Hammond, and has been defended very recently by Senator.1 It is based rather upon the known physiological connection between the cerebellum and certain forms of ataxia rather than upon anatomical changes, since Menzel's is the only case in which cerebellar disease has been found, and in it there was only a diminution in the number of the cells of Purkinje without alteration of those existing. According to this view the spinal changes are secondary. The uniformity with which changes have been found in definite regions of the cord in all cases makes it, I believe, perfectly safe to regard that organ as the primary seat of the affection. As to what the nature of the lesion is, however, and as to whether the involvement of the lateral columns is a necessary factor there is much room for dispute. The disease is not congenital in the sense of appearing at birth, since the most frequent age at onset is in the period between the sixth and the tenth year. The cord, therefore, is well adapted to the needs of infancy and sufficiently well developed to overcome the physiological ataxia of that period, and hence there is no ground for the belief that there is an actual anatomical arrest of development. On the other hand, acute disease is not needed to produce cordal breakdown, since, while in a few cases acute and usually infectious diseases have precipi- tated the symptoms, in most instances the condition has developed of itself and without dependence on disease of other organs. Again, in- heritance, either direct or indirect, while a very frequent factor, is not necessary, since some undoubted cases have been sporadic. Indeed, as 1 Berliner klinische Wochenschrift, 1893, No. 21, p. 489. 6 Charles W. Burr. to this whole matter, we must admit the view accepted by Gowers that the ultimate cause is a congenital tendency of development by which the affected elements have a briefer period of vital endurance than the other tissues of the organism. There is much uniformity in certain respects in the autopsies made in cases of this disease. In all cases the cord has been small in volume, and the posterior columns, especially those of Goll, have been diseased. In almost all, the lateral columns have been affected sometimes diffusely and sometimes in the crossed pyramidal and direct cerebellar tracts almost exclusively. As a rule, the direct pyramidal tracts have been involved. Inflammation of the central canal has been marked in some cases, occasionally with the presence of distinct but small cavities. The gray matter of the anterior horns has never been found seriously affected, but the cells of Clarke's columns are often shrunken and with- out processes. Degeneration of the posterior horns has been noticed. The cutaneous nerves have been examined but seldom. In Auscher's case great numbers of apparently embryonic fibres were found, but no degeneration. The anterior nerve-roots have never been found diseased, the posterior practically always. These conditions have been interpreted very differently. Fried- reich's first opinion, founded upon three autopsies, was that the essen- tial lesion is a chronic inflammation of the posterior columns of the cord, beginning in the lumbar region and due to the meningitis present. His final conclusion, based on a fourth autopsy, was that there is a lack of development of the cord in which posterior sclerosis develops, fol- lowed by meningitis, which in its turn produces sclerosis of other tracts. Everett Smith1 also holds that the lesion is spread by means of the meningitis. Kahler and Pick2 hold that there is not simply a posterior sclerosis, but a combined systematic degeneration, an upward degeneration of the posterior columns, downward of the direct and crossed pyramidal tracts, and of the direct cerebellar tracts and columns of Clarke. The clinical history of this case was scanty, and when the patient came under observation motor weakness was so great that the presence or absence of ataxia could not be determined. In Brousse's3 case there was marked inflammation of the central canal, which was filled with small deeply-stained cells. He holds that the primary lesion, posterior sclerosis, is spread diffusely by means of the central inflammation to other parts of the cord. 1 Boston Medical and Surgical Journal, October 15, 1885. 2 Archiv fur Psychiatric, etc., Bd. vm, p. 251. 8 De 1'Ataxie H6r6ditaire, Paris, 1882. Pathology of Friedreich's Ataxia. 7 Pitt1 believes that there is an inherited tendency to vascular de- generation, and that since the posterior columns are the most vascular they suffer first and most. There is not so much an overgrowth of neuroglia as an imperfect development of the medullary sheaths fol- lowed by degeneration. The primary cause is probably an endarteritis. Rutimeyer1 regards it as a combined system disease. Blocq and Marinesco3 hold it to be a developmental disease due to a sclerosis, vascular in origin, and occupying definite regions of the cord. Dejerine and Letulle4 advance an entirely new idea in the path- ology of the disease. Re-examining a case previously reported by Letulle and Vaquez,5 and using the method first employed by Malassez to differentiate neuroglia from mesoblastic connective tissue, they found that the lesion of the posterior columns was a pure neurogliar sclerosis, while that of the pyramidal and cerebellar tracts was a vascular or con- nective tissue sclerosis. They hold that the former is a type found in no acquired sclerotic disease, for example, tabes dorsalis and multiple sclerosis, and hence affirm that Friedreich's ataxia is a gliosis of the posterior columns, a sclerosis of ectodermic origin. The affection of the lateral tracts they regard as secondary. Auscher * also reports a case which he describes as a pure neuro- gliar sclerosis. It is the more interesting since there was no degenera- tion except in the posterior columns. The patient died four years after the onset. Incoordination appearing at 25 years was the first symp- tom. Presently fulgerant pains, scoliosis, trouble of speech, choreiform movements of the head and body, nystagmus, abolition of the reflexes, and Argyle Robertson pupil appeared. Sensation remained normal. The fulgerant pains and pupillary symptoms take the case out of the common type. We are hindered very much in the endeavor to find the essential lesion by the fact that opportunity for examination comes only after the disease has lasted several, usually many, years. No theory as yet developed explains the whole question satisfactorily. I believe, how- ever, that the view that a neurogliar sclerosis of the posterior columns is the primary lesion approaches most nearly to the truth. I am greatly indebted to my friend, Dr. A. A. Stevens, for his kindness in drawing the accompanying illustrations. 1 Guy's Hospital Reports, Vol. xliv, p. 369. 2 Virchow's Archiv, Bd. ex, p. 215. 3 Archives de Neurologic, May, 1891. 4 Archiv. de Neurologic, May, 1891. 3 L,a Semaine Medicale, March 12, 1890. 6 La Semaine Medicale, July 30, 1890.