J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.27.4.332 on 1 August 1964. Downloaded from J. Neurol. Neutrosurg. Psychiat., 1964, 27, 332
Superficial haemosiderosis of the central nervous system
B. E. TOMLINSON AND JOHN N. WALTON From the Departments ofNeuropathology and Neurology, Regional Neurological Centre, the General Hospital, Newcastle upon Tyne
In 1940 Noetzel reported two cases of slowly for investigation on 13 May 1959. For two years she had progressive neurological illness in which, at necropsy, suffered from paroxysmal headaches with vomiting which the meninges overlying the brain and spinal cord and had become much more severe in the last six months. the peripheral areas of the brain, cerebellum, and During the headache the patient would often experience cord were found to be rust-brown in blurring of vision and transient right-sided hemianopia. spinal colour. Independently of these headaches she had begun to Iron pigment was found in the meninges, glial cells, experience brief episodes lasting only a few seconds in within mesodermal cells and around blood vessels in which she lost the power of speech and would go 'blank' the cortex, and in the lining of the cerebral ventricles, for a few seconds. Tongue-biting and incontinence had and the pigmented cerebellar convolutions were never occurred. Recently too she had seemed to become disorganized. The author concluded that this condi- slow and disinterested and intermittently drowsy and her tion was due to the diffusion of blood pigment into appetite and weight had diminished considerably. Protected by copyright. the marginal zone of the central nervous system and On examination on admission the patient was conscious suggested that the condition was probably the result and coherent but seemed dull, lethargic, and disin- terested. She complained intermittently of right-sided of chronic subarachnoid bleeding. Subsequently, headache. The optic fundi were normal, but examination however, additional cases were reported by Lewey of the visual fields revealed a congruous right upper and Govons (1942), Cammermeyer (1947), Neumann quadrantic field defect. There were no other clear-cut (1948, 1956), Garcin and Lapresle (1957), Rosenthal neurological signs on examination. Survey views of the (1958), and McGee, van Patter, Morotta, and skull showed no significant bonv abnormality; the pineal Olszewski (1962). Neumann (1948, 1956) concluded gland was faintly calcified but could not be accurately that the pathological changes in the central nervous identified in the antero-posterior view. A lumbar puncture system which she observed in her two cases were the was not performed. During her stay in hospital the result of haemochromatosis of the central nervous patient was observed to have recurrent attacks of minor epilepsy. An E.E;G. was abnormal; it showed generalized system. Others, however, have pointed out that the paroxysms of slow activity of both theta and delta fre- pigment deposits consist of haemosiderin and suggest quency suggestive of epilepsy of central origin. There was that in most, if not all, cases this disorder results no clear evidence of a focal lesion in either cerebral from repeated or long-continued bleeding into the hemisphere. Bilateral carotid arteriography was per- subarachnoid space. In all, 11 cases of this type have formed on 19 May. No angioma or other vascular mal- now been reported in the world literature. They have formation and no pathological circulation was demon- http://jnnp.bmj.com/ shown a remarkably consistent clinical picture strated in either hemisphere, but Dr. G. L. Gryspeerdt characterized particularly by progressive dementia, commented that the appearance suggested a degree of nerve deafness, and cerebellar ataxia, and the patho- dilatation of both lateral ventricles. The patient was treated with anticonvulsants and logical changes in the reported cases have also been ergotamine preparations; the headaches improved and strikingly uniform in character. Table I summarizes she became more alert; she was discharged home on 27 details of the cases reported to date and we give May 1959. She was seen again on 11 July and had below detailed clinical and pathological observations deteriorated. Her speech had become slurred and her gait in the first case of this type to be reported from Great unsteady, she was continuing to lose weight, and her on October 1, 2021 by guest. Britain. 'blackouts' were more frequent. The patient was re- admitted to hospital on 14 July. She was found to be confused, disorientated, and lethargic and formal intel- CASE REPORT lectual testing indicated a degree of early dementia. There was some neck stiffness and the visual field defect was CLINICAL DETAILS An untrained children's nurse, aged unchanged. Psychometric tests showed that she appeared 16 years, was admitted to the Newcastle General Hospital to be functioning at the 'high-grade feeble minded' level 332 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.27.4.332 on 1 August 1964. Downloaded from Suiperficial haemosiderosis of the central nervous system 333 TABLE I 12 REPORTED CASES OF SUPERFICIAL HAEMOSIDEROSIS OF THE CENTRAL NERVOUS SYSTEM (INCLUDING PRESENT CASE) 9r and Age and Clinical Features Pathological Features Other Features Sex of Other than Haemosiderosis Patient Duration Cerebellar Nerve Dementia Sphincter Spastic ity of Illness Ataxia Deafness Dis- Subarachnoid Aetiology turbance Bleeding zel 1940 M 47 Not Not + + Not - Xanthochromia Carcinomatosis of Positive C.S.F. known known known meninges. Wassermann re- Ca of stomach action, fixed pupils, absent reflexes zel 1940 F 59 Not Not Not Not Not Xanthochromia Not found at Absent knee jerks, known known known known known ('Haemorrhagic necropsy sluggish pupils meningitis') y and M 36 7 years + + + + + Xanthochromia, Not found at )ns 1942 bleeding suspected necropsy nann 1948 M 47 12 years + + -rv + + 'Cherry-sized mass Alcoholism in fourth ventricle' nann 1956 F 55 17 years + + + -V T -_ None found ? Severe closed head injury nermeyer *Not described + Aneurysm of vertebral artery in and F 47 10 years T -V- -L ± Suspected, not Not discovered Diabetes mellitus, -sle 1957 proved loss of position sense in legs; cirrhosis of liver Protected by copyright. rithal M 67 Not + + Not ± Not found Pyelonephritis, known known chronic bronchitis, emphysema nthal M 27 Not Because of widespread dissemination of the causal ++ Oligodendroglioma, known neoplasm, signs and symptoms due to haemosiderosis subarachnoid and could not be properly assessed intraventricular spread ec, van M 52 10 _ -V - + _ -V+ Ependymoma of Absent ankle jerks. r, Morotta, months (? due to filum terminale ? due to tumour )lszewski tumour) M 59 10 years ++ - Not +±+ Intracranial known angioma inson and F 16 2 years + + + + + + + Ependymoma of n 1964 Terminal Terminal lateral ventricle
(I.Q. 67). Her recent memory was severely impaired, a depth of 5 cm. The cerebrospinal fluid was deeply blood- there was marked fluctuation in her performance, and stained with a mixture of fresh and recent blood. Air some of the test results suggested recent organic deteriora- passed freely from the left to the right ventricle and a tion. Neck stiffness increased and the patient was now total of 40 ml. of cerebrospinal fluid was replaced with http://jnnp.bmj.com/ developing a progressive bilateral deafness of perceptive air. Radiographs demonstrated multiple filling defects in type. There was moderate symmetrical cerebellar ataxia the lateral ventricles which were interpreted as being due of the arms and legs, but the tendon reflexes were active to patchy coagulum and it was decided that no surgical and equal, the plantar responses flexor. A lumbar treatment was possible. Shortly afterwards the patient puncture on 12 August gave fluid under pressure of developed retention of urine with overflow and bilateral 120 mm. cerebrospinal fluid; the fluid was uniformly and extensor plantar responses. She gradually lapsed into deeply bloodstained. The packed cell volume in the fluid coma and died on 3 September 1959. was 80% and the protein content of the deeply xantho- chromic supernatant fluid was 5.0 g. per 100 ml. An PATHOLOGICAL FINDINGS At necropsy the body was that on October 1, 2021 by guest. E.E.G. was more abnormal than the previous recording; of a fully developed but very thin girl, 5 ft. 2 in. tall and it was now somewhat asymmetrical, showing more slow weighing 44 kg. (5 st. 4 Jb.). There was no skin pigmenta- activity on the left side and particularly in the left tion. In the internal organs, apart from broncho- tempoial region, but no clear-cut focal abnormality was pneumonia with abscess formation, there were no signi- demonstrated. Ventriculography was performed by Mr. J. ficant abnormalities outside the central nervous system. Hankinson on 14 August 1959. The intracranial tension No pigment deposition or fibrosis was present in any of was incdeased; the lateral ventricles wele encountered at the general organs. The scalp and skull and dura mater J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.27.4.332 on 1 August 1964. Downloaded from
334 B. E. Tomlinson and John N. Walton were normal. In the subarachnoid space of the spinal The pigment was almost entirely iron-containing, cord and brain, particularly in the basal cisterns and over giving a positive Perls's reaction. In unstained sections a the pons and medulla and anterior third ofthe cerebellum, large quantity of pigment occurred as yellowish-brown there was deep brown pigmentation with numerous ad- or brown granular particles up to 4 or 5 j* in diameter, hesions and with brown staining of the outer layers of the all apparently within macrophages. Fine pigment granules cerebral cortex and spinal cord (Fig. 1). There was no were present within macrophages in the pia arachnoid fresh blood in the subarachnoid space. The basal vessels but some lay free and a little was present within fibro- were embedded in adhesions and pigment but were all blasts. Very fine particles of iron-positive pigment, thin-walled and apparently normal. The origins of all the approximately 1 ,u in size, were present within the cyto- cranial nerves were pigmented, the pigmentation stopping plasm of numerous hypertrophied astrocytes and in some abruptly at their exit from the subarachnoid space. Some macrophages. In astrocytes these particles were most nerves were only slightly pigmented, the fifth and sixth numerous at the base of the astrocytic processes, and being only yellow at the origins, but the seventh and similar particles were seen in the adventitia and outer eighth were nigger brown, the latter for 7-8 mm. and media of blood vessels in the pia arachnoid and in the the pigmentation extended for 2-3 mm. into the brain periphery of round, hyaline bodies which formed a substance. The olfactory bulbs and the optic nerves prominent feature of the histological preparations (Figs. within the skull were deep brown in colour. In the latter 4 and 5). Some non-granular iron-positive material was pigmentation extended to the posterior surface of the present within these hyaline bodies and macrophages. In bulb but gradually diminished from the optic foramen iron-stained preparations almost no unstained pigment peripherally. The origins of all the spinal nerves were apart from a little lipochrome within an occasional deeply pigmented. Arachnoid fibrosis, which was marked neurone could be identified. The pigment was removed at the base of the brain, had apparently obliterated the from sections by treatment with 5% oxalic acid. It is con- foramina of Lushka but not the foramen of Magendie. cluded, therefore, that almost all of the pigment deposited There was considerable dilatation of both lateral in the central nervous system in this case was haemo- ventricles and intense brown pigmentation of a 1 mm. siderin. Attempts to identify other pigments were almost layer ofsubependymal tissue in all the ventricles. Multiple completely unsuccessful. A very occasional macrophage deep brown, ependymal granulations were present in the spinal cord and cerebellar cortex contained sudano-Protected by copyright. throughout all the ventricles and the left posterior horn philic material and a very occasional neurone a small was filled by a solid, vascular, granular tumour (Fig. 2). quantity of lipofuscin. Haematoidin (bilirubin), calcium, Two small deposits of tumour were visible in the anterior and melanin were not found. The pigment will, therefore, end of the left lateral ventricle, and a further deposit, from now on be called haemosiderin. 5 mm. across, lay in the hypothalamus at the level of the The hyaline bodies, previously mentioned, were present tuber cinereum. Pigmentation was approximately i mm. in both neuronal and non-neuronal areas and in some deep over most parts of the cortex, 1 mm. deep beneath parts of the outer cortex were very numerous (Figs. 4 and the ependyma, 2-3 mm. deep over the periphery of the 5). They stained with differing degrees of eosinophilia and pons, cerebral peduncles, the quadrigeminal bodies, and varied in size from 15 to 50 IA; they were oval or round, the medulla and the whole of the cord (Figs. 3 and 8). The and usually well defined, appearing to have a limiting entire thickness of the hypothalamus was pigmented. membrane. In many, fine particles of haemosiderin were Pigmentation of the cervical cord left only a central un- present, particularly in the periphery, and all gave a posi- pigmented zone 4 mm. across and the thoracic and tive reaction for haemosiderin, though the intensity varied lumbar cord showed an even smaller central zone of from a faint to a very strong reaction. The larger bodies unpigmented tissue. The anterior third of the cerebellum contained no nucleus, but an occasional small body had was pigmented to a depth of 1 cm., with visible shrinkage a minute flattened peripheral nucleus. They contained no and disorganization of folia, particularly those of the demonstrable lipid, showed no metachromasia with vermis and of the structures in the roof of the upper end toluidine blue but were slightly metachromatic with of the fourth ventricle. The central lobule and flocculus methyl violet, only faintly positive with periodic-acid http://jnnp.bmj.com/ were not identifiable, being reduced to a deeply pig- Schiff reagent, and were negative with carbol fuchsin or mented mass of honeycombed glial tissue. in attempts to stain by Schmorl's method. They showed The tumour in the lateral ventricle was a papillary type only a faint affinity for silver. It appears likely that the of ependymoma with a vascular stroma which included majority are degenerating macrophages since occasionally many thin-walled blood vessels, some of which were small groups of them were found in perivascular spaces. thrombosed. Within the tumour itself there was very Although very numerous in this condition and in some little pigment; it was present in the interstitial tissue, but of the previous cases reported, identical bodies aie not within the tumour cells. The granular appearance of occasionally found in old haemorrhagic infarcts and the ventricles was due to subependymal gliosis, with presumably result from bleedingand release of breakdown on October 1, 2021 by guest. much pigment in macrophages and encrusting astrocytes. products of red cells in the central nervous system. Such granulations were present throughout all the In all the pigmented areas there was macrophage ventricular system, in the aqueduct and in the floor and reaction, marked astrocytic proliferation, and in some roof of the fourth ventricle (Figs. 2 and 3). The ependymal places severe gliosis. In some areas there was actual cells contained either no pigment or only a few minute necrosis and wherever pigmentation was heavy, damage particles, the pigment being in the subependymal tissues. to neurones, myelin sheaths, and neurofibrils was present. The choroid plexuses were deeply pigmented. In many areas marked endothelial swelling in small J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.27.4.332 on 1 August 1964. Downloaded from Superficial haemosiderosis of the central nervous system 335 Protected by copyright.
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FIG. 1. Pigmentation and arachnoid thickening is particu- larly prominent over the pons, medulla, and anterior third ofthe cerebellar hemispheres. The bifurcation ofthe basilar artery is hidden by pigment which has been removedfrom the interpeduncular cistern.
FIG. 2. Horizontal brain section showing the ventricular dilatation, pigmented granular ependymitis, and the tumour http://jnnp.bmj.com/ filling the posterior horn of the left lateral ventricle. FIG. 3. Peripheral haemosiderin deposition at the level of the rostral limit of the fourth ventricle. Note the sub- ependymal pigmented granulations in the roof and floor ofthefourth ventricle. Perls x 4. on October 1, 2021 by guest.
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FIG. 4 FIG. 5 FIG. 4. Apex of a frontal lobe convolution. The cellular, heavily pigmented pia arachnoid is adherent in one place to the grossly disorganized superficial cortex. Haematoxylin and eosin x 58. FIG. 5. Higher-power view of the cortex of Fig. 4 showing a network of capillaries, heavily pigmented macrophages, and several hyaline bodies. A hyaline bodv and a neurone lie adjacent to an arteriole showing cellular subintimal hyperplasia. Haematoxylin and eosin x 220. arterioles was present, suggesting that some of the The incompletely destroyed folia had a characteristic necrosis might be secondary to vascular occlusion. appearance; pigmentation, not necessarily heavy, was In all areas of the cerebral cortex, an occasional limited to the apex of the folium where neuronal destruc- macrophage and iron-encrusted astrocytes were present tion was out of proportion to the degree of pigmentation, in the molecular layer. Pigmentation was heaviest over and resulted in marked thinning and collapse of thehttp://jnnp.bmj.com/ the apices of the convolutions, reaching the third layer of molecular layer with complete loss of the Purkinje cells. the cortex, and masses of pigmented macrophages were Usually the cap of granular cells was also destroyed, but present around blood vessels, and in clumps and singly a thick layer of proliferated Bergmann astrocytes in the cortex, and throughout these areas there was remained, their processes encrusted with haemosiderin. marked astrocytic proliferation. In such areas there was The periphery of the spinal cord was heavily pigmented, severe loss of neurones (Figs. 4 and 5). Occasional haemosiderin being within macrophages and astrocytes, shrunken or very pale-staining neurones could be found but pigment was particularly heavy in the anterior horns in the affected areas but in no identifiable neurone could (Fig. 8), though the neurones appeared to be entirely iron pigment be demonstrated. Similar appearances were normal. The pigmented periphery of the cord showed on October 1, 2021 by guest. present in all exposed neuronal areas of the brain, such partial demyelinization with numerous beaded and as the quadrigeminal bodies, and the pulvinar of the swollen myelin sheaths and loss and fragmentation of thalamus and the hypothalamus. neurofibrils. In the cerebellum more intense destruction had Large clumps of macrophages and some astrocytes occurred, the midline roof structures in the rostral end were present at the points of exit of cranial nerves and at of the fourth ventricule being reduced to pigmented glial the origins of ventral and dorsal nerve roots in the cord. scars, as were many of the collapsed folia (Figs. 6 and 7). The exit zones of the third and fourth nerves were only J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.27.4.332 on 1 August 1964. Downloaded from
Superficial haemosiderosis of the central nervous system 337 Protected by copyright.
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FIG. 6. Destruction ofthe cerebellar hemisphere. Normal j ,^ folia' < with heavily stained zones ofgranule cells lie deep to the eroded surface, where the outline ofdestroyedfolia and the characteristic loss ofgranhle cells at the apex ofpartly Pwiaffected folia are visible. Haematoxylin and eosin x 5. .-A FIG. 7. Varying destruction of cerebellar folia. In the t .h .. the solid mass cells which F....
II1( i. IY FIG. 8. Perls's reaction on a section ofthe thoracic cord on October 1, 2021 by guest. showing the heavy peripheral pigmentation, the small central unpigmented zone, and the heavily pigmented anterior horns. x 10. J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.27.4.332 on 1 August 1964. Downloaded from
338 B. E. Tomlinson and John N. Walton
slightly involved, but the second and eighth showed present in the remaining cases but were not com- extremely heavy deposits of iron with considerable myelin mented upon specifically in the case reports or else loss, and iron deposition and astrocytic proliferation were obscured other extended into the superficial areas of the dorsal and they by neurological findings. ventral cochlear nuiclei. The optic nerves showed little Turning to the pathological findings, all cases showed loss of myelin or nerve fibres. the characteristic brown staining ofthe meninges and of peripheral areas of the central nervous system, DISCUSSION usually with a striking degree of cerebellar degenera- tion and atrophy. In seven there was definite The symptoms and the physical signs in this case evidence of subarachnoid bleeding and in three it was clearly resulted from the combined effects of the suspected; only in two was there no evidence of tumour and the haemosiderosis. Repeated small meningeal haemorrhage. In one case the haemor- haemorrhages were presumably responsible for the rhage was due to an intracranial aneurysm, in two recurrent severe headaches. Subsequently hydro- to the presence of an ependymoma (of the filum cephalus, progressive dementia, and chronic sub- terminale and ofthe left lateral ventricle respectively), arachnoid bleeding brought to mind the possibility in one to a cerebral vascular malformation, in one of an intraventricular tumour such as a choroid to carcinomatosis of the meninges, and in one to an plexus papilloma, but the findings on ventriculo- oligodendroglioma. In the remaining cases no definite graphy were inconclusive. The haemosiderosis of the source of haemorrhage was identified (Table I). central nervous system was almost certainly respon- There is no evidence in this case, as there has been sible for the cerebellar ataxia, the nerve deafness, and none in the others in the literature, of generalized for much of the mental deterioration. This latter haemochromatosis and there is no reason to believe could be accounted for by the widespread though that this is a form of that disease localized to the relatively superficial cortical destruction, but the central nervous system. Cammermeyer (1947), associated hydrocephalus, possibly due to obstruc- McDougal and Adams (1950), and Adams (1956)Protected by copyright. tion of the fourth ventricular foramina, could have pointed out that in haemochromatosis deposition of been a contributory factor. The involvement of the iron in the central nervous system is extremely eighth nerve at its origin and of the peripheral parts limited. The choroid plexuses are intensely pig- of the cochlear nuclei presumably caused the nerve mented, but the deposition of iron pigment is con- deafness and the severe cerebellar destruction fined otherwise to a few small foci in relation to the accounted for the cerebellar symptoms and signs. ventricular system and to neuro-secretory areas, In the case of Neumann (1948) marked destruction e.g., area postrema, pineal, and infundibulum. Pig- of anterior horn cells had apparently occurred as a mentation of the type described in the 12 cases we result of the haemosiderin deposition. In that case, have discussed has never been found in association however, the illness was protracted, lasting more than with systemic haemochromatosis. 12 years. We observed marked pigmentation of the In cases of superficial haemosiderosis, by contrast, anterior horns at necropsy in our case, but signs of the iron deposition has been found in those areas lower motor neurone weakness were not detected bathed by circulating cerebrospinal fluid. Thus, the during life and there was no neuronal degeneration, cerebral hemispheres, the cerebellum, and the outer though the latter change might have developed had layers of the cord and the brain-stem are involved. the illness lasted longer. In the case we have described The subependymal layers around the ventricles have the partial demyelination and fibre damage in the been found to be pigmented in a number of cases;http://jnnp.bmj.com/ periphery of the cord could well have given rise to in each of these a focus of intraventricular haemor- sensory disturbances, e.g., loss of vibration and posi- rhage was present. In our case the haemorrhage was tion sense in the legs, but the patient became so clearly arising from the ependymoma in the lateral demented that accurate sensory testing was not ventricle. The rarity of this condition in no sense possible. However, signs of pyramidal tract dys- detracts from the view that it is the result of frequent function only appeared as a terminal event. or continuous haemorrhages occurring into the sub- The clinical findings in the 12 cases reported to arachnoid space or cerebral ventricles. Although sub- date, including our case, may therefore be sum- arachnoid bleeding is common, the cases in which it on October 1, 2021 by guest. marized by saying that eight showed bilateral nerve occurs repeatedly or over a long period of time must deafness, seven bilateral cerebellar ataxia, eigl4 had be rare. It should also be noted that the changes in evidence of bilarteal pyramidal tract disease, four the pia arachnoid and in the superficial cortex close retention of urine with overflow, four absent reflexes to a ruptured aneurysm are similar, though much or impaired vibration sense in the legs, and at least less severe. Thus there is fibroblastic proliferation in seven showed progressive dementia in the terminal the pia arachnoid with deposition of haemosiderin stages. Several of these features may have been in macrophages as well as in some fibroblasts and in J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.27.4.332 on 1 August 1964. Downloaded from
Superficial haemosiderosis of the central nervous system 339
the adventitia of blood vessels. Often there is con- could be accounted for by either root or cord in- siderable astrocytic proliferation in the outer layers volvement. The bladder disturbances seen in our of the cortex; the astrocytes are often aligned in rows patient and reported in a number of those previously and in some places their processes are encrusted with described probably result from involvement of the iron pigment. The curious large hyaline and sacral segments of the cord or sacral roots. The bi- haemosiderin-positive bodies found in our case and lateral pyramidal tract signs present in the majority in a number of the reported instances are also to be of the cases can be explained either by the involve- found occasionally in relation to areas of old cerebral ment of the pyramids within the medulla or by haemorrhage or haemorrhagic infarction. Further- degeneration of the peripheral parts of descending more, Iwanowski and Olszewski (1960) have studied tracts in the spinal cord. In our case demyelination the effects ofmultiple injections of heparinized blood, was slight in these areas and signs of pyramidal of haemolysed red cells, and of the iron preparation tract dysfunction were only found terminally. Imferon into the cisterna magna of dogs. They found that similar lesions in the cerebellar folia, as well as SUMMARY pia arachnoid pigmentation, incrustation of subpial The case is reported of a 16-year-old girl who gave astrocytes with iron-containing pigment, and, in some a two-year history of recurrent headaches and of a instances, foci of cortical necrosis occurred when recurrent right-sided visual field defect. Later she multiple injections of blood were given. The evidence, developed minor epileptic seizures, nerve deafness, therefore, that this condition is associated with dementia, cerebellar ataxia, urinary retention with haemorrhage into the subarachnoid space or overflow, and finally signs of bilateral pyramidal ventricles seems to be conclusive. It cannot, however, tract dysfunction. The cerebrospinal fluid was deeply be stated categorically that it is the deposition of blood-stained. At necropsy a vascular ependymoma haemosiderin itself which results in degeneration. of the left lateral ventricle was discovered and there This deposition may merely be the sign of haemor- was widespread staining of the meninges and of Protected by copyright. rhage rather than the explanation for necrosis. In- superficial and periventricular areas of the cerebral deed one piece of evidence strongly suggests that it hemispheres, cerebellum, brain-stem, and spinal cord is not haemosiderin itself which causes the necrosis; with haemosiderin. In the deeply-stained areas there although neurones in many areas are apparently was usually widespread degeneration of neurones destroyed, and in the cerebellum necrosis of all and of glial cells; superficial demyelination was ob- tissues except the hypertrophied astrocytes and served not only in the brain-stem and spinal cord macrophages is to be found, little, if any, haemo- but also in cranial nerves and nerve roots. siderin is found within neurones. In our case haemo- This is the twelfth case of haemosiderosis of the siderin deposition was at its heaviest in the anterior central nervous system to be reported in the world horns of the spinal cord, yet the neurones themselves literature. The clinical and pathological findings in were intact and contained no haemosiderin. It thus these 12 cases are discussed. The predominant clinical seems probable that some other breakdown product features of the illness are nerve deafness, dementia of the blood and plasma liberated into the sub- and cerebellar ataxia, with eventually, retention of arachnoid space is responsible for tissue damage urine with overflow and other signs of spinal cord rather than the haemosiderin itself and that the latter disease. Reasons are given for concluding that the is merely an obvious and striking indication that syndrome results either from repeated small haemor- repeated previous bleeding has occurred. rhages or from continuous bleeding within the http://jnnp.bmj.com/ The relatively constant occurrence of the three subarachnoid space over a prolonged period of time. main symptoms and signs of this condition, namely, nerve deafness, cerebellar ataxia, and dementia, We are grateful to E. Manns, A. Willis, and Miss R. Allen shows that the eighth nerves and perhaps the peri- for their help. pheral parts of the cochlear nuclei constantly suffer, REFERENCES as do the cerebellum and the superficial layers of the cerebral cortex. It is, however, clear that other areas, Adams, R. D. (1956). J. Neuropath. exp. Neurol., 15, 215. Cammermeyer, J. (1947). Ibid., 6, 111. particularly the anterior horns, roots, and long tracts Garcin, R., and Lapresle, J. (1957). Rev. neurol., 97, 417. on October 1, 2021 by guest. in the spinal cord, may also be severely affected and Iwanowski, L., and Olszewski, J. (1960). J. Neuropath. exp. Neurol., 19, 433. may give rise to some of the predominant symptoms. Lewey, F. H., and Govons, S. R. (1942). Ibid., 1, 129. Thus the impairment of position sense and of vibra- McDougal, D. B., and Adams, R. D. (1950). Ibid., 9, 117. McGee; D. A., van Patter, H. J., Morotta, J., and Olszewski, J. (1962). tion sense in the legs reported in the case of Garcin Neurology (Minneap.), 12, 108. and Lapresle (1957) would presumably be explained Neumann, M. A. (1948). J. Neuropath. exp. Neurol., 7, 19. by degeneration ofmyelin and axons in the peripheral - (1956). Ibid., 15, 214. Noetzel, H. (1940). Arch. Psychiat. Nervenkr., 111, 129. parts of the cord, and absent lower limb reflexes Rosenthal, P. (1958). Dtsch. Nervenheilk., 178, 431.