the nosological position of concentric lacunar ...j. neurol. neurosurg.psychiat., 1970, 33, 131-137...

J. Neurol. Neurosurg. Psychiat., 1970, 33, 131-137

The nosological position of concentric lacunarleucoencephalopathy

S. CURRIE,1 A. H. ROBERTS, AND H. URICHThe London Hospital, Whitechapel, London

In 1960 Grcevic reported an apparently unique case.The patient, a woman, had been well until the age of30. In the following three years she became 'almostblind', her vision deteriorating in an illness character-ized by exacerbations and partial remissions. Shethen became progressively demented, developingabruptly a hemiparesis and aphasia six monthsbefore her death in epileptic status at the age of 35.At necropsy extensive changes were found in thewhite matter of the rostral two-thirds of the cerebralhemispheres consisting of concentric lacunae sep-arated by glial septa. In the affected areas there wastotal loss of axons and myelin sheaths. The lesionsbore a superficial similarity to the concentric sclerosisof Balo (1928) from which they differed in beingdestructive and not demyelinating. The author dis-cussed the nosological position of the conditionwhich he named 'concentric lacunar leucoencepha-lopathy', and its relationship to demyelinating dis-eases, without reaching definite conclusions.We report a case in which the association of similar

lesions in the white matter with patchy demyelinationin the optic pathways and an acute necrotizingmyelopathy suggested a close relationship to thedemyelinating diseases, particularly to neuro-myelitis optica.

CASE REPORT

CLINICAL HISTORY Mr. G.R., a labourer, was admittedto his local hospital at the age of 64 in August 1966 withpainless deterioration in the vision of both eyes. Thisappeared to have developed suddenly overnight. Whenhe was seen two weeks later a left homonymous fielddefect was found which over the next two weeks pro-gressed to complete blindness. His memory had becomedefective during the same period. Vision in the left eyewas said to have been poor for years, but three yearsearlier severe myopia had apparently been corrected byan optician. Two weeks after the sudden deterioration invision lumbar puncture was performed; the cerebrospinal'Present address: Newcastle General Hospital, Newcastle upon Tyne,4.

fluid was found to contain 208 mg./100 ml. protein but noother abnormality, and manometrics were normal. TheWassermann reaction was negative in blood and fluid. Itwas thought that the patient might have a suprasellarlesion and he was transferred to a neurosurgical centre.There he was found to be disorientated. The eyes weremyopic and the optic discs were noted to be pale, butthere appeared to be normal pupillary reactions despiteimperception of light. There was a mild impairment ofsuperficial sensory perception over the left side of thebody. At ventriculography the fluid was xanthochromicand turbid, containing 375 red blood cells and 4 whitecells/cu. mm and 140 mg/100 ml. of protein; mano-metrics and radiology were normal. A right vertebralangiogram was normal. Infarction of both occipitallobes was considered the most probable diagnosis.The patient's condition then remained unchanged until

five months later in January 1967 he developed a suddenleft hemiplegia from which he recovered within 24 hours.Three months after this a grand mal epileptic attackoccurred, followed by transient left-sided weakness. Hewas admitted to a local hospital again. There he wasfound to be orientated and co-operative, but blind with-out light perception, the pupils reacting only sluggishlyto light. The optic discs were noted to be pale. Nodisturbance of left-sided motor or sensory function wasapparent. He was normotensive. An ESR and bloodcount were normal. A right carotid angiogram demon-strated atheroma at the origin of the internal carotidartery but no abnormality of the intracerebral vessels.The patient was treated with phenobarbitone and hadonly one further major seizure during the following year.He then remained well again until October 1967, five

weeks before his death, when a sudden episode of weak-ness of both legs occurred lasting half an hour. Thisrecurred within a fortnight, again transiently, on thisoccasion after a long walk. Two days later he awoke inthe night with severe lumbar pain and on the followingmorning was incontinent of urine and unable to move hislegs. On admission to hospital a dense flaccid paraplegiawas found with cutaneous sensory loss from the fourththoracic dermatome caudally; bladder drainage wasrequired.He was transferred to the London Hospital (no. 369575)

the next day. On admission he was apyrexial, but drowsy,disorientated, and euphoric. He was blind without lightperception in either eye. Pupillary reactions were present

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S. Currie, A. H. Roberts, and H. Urich

but not in response to light, and were thought to indicatereflex attempts at convergence. The left eye was highlymyopic and both optic discs were atrophic. The retinaeand vessels were normal. Neck stiffness was present.Initially a flaccid paraplegia with slight weakness of thewrist extensors on the left was noted. The tendonreflexes were sluggish in the arms, with the exception ofthe triceps, which were brisk, and absent in the legs.There was little response to plantar stimulation. Respir-ation was largely diaphragmatic, only the upper inter-costals contracting. There was anaesthesia from thesecond thoracic dermatome caudally. Later the same daythe sensory level was found to have risen to the fourthcervical dermatome on the left and to the eighth on theright, and breathing had become entirely diaphragmatic.Routine investigations including peripheral blood exam-ination and radiographs of the chest and spine werenormal. The ESR was 20 mm in one hour. The cerebro-spinal fluid contained 355 white cells/cu. mm, pre-dominantly neutrophils, 40 mg/100 ml. protein, and 90/100 ml. sugar. The Wassermann and Lange colloidalgold reactions in the fluid were negative and no organismswere seen or cultured. A myelogram was normal. Apresumptive diagnosis of infarction of the cord was made.Within two days the sensory level had risen to the secondcervical dermatome, the arms had become asymmetricallyweak with slight power remaining only proximally indeltoids and biceps, while the tendon reflexes could nolonger be elicited. He continued to deteriorate, the armsbecoming flaccid and totally paralysed the day before hisdeath. He died on 6 November 1967, 11 days after theonset of persistent leg weakness.

NECROPSY FINDINGS (PM 354/67) The following featureswere observed: concentric lacunar leucoencephalopathy;retrobulbar neuritis; acute myelomalacia; deep femoralvein thrombosis; pulmonary embolism; and acutehaemorrhagic cystitis.

EXAMINATION OF THE NERVOUS SYSTIm Macroscopic Thebrain (1,176 g) was externally normal. Coronal sectionsof the cerebral hemispheres revealed extensive lacunarsoftening in the white matter, involving both occipitallobes, parts of the right parietal and right temporal lobes,and the splenium of the corpus callosum (Fig. 1). Thelacunae were arranged in approximately parallel, con-centric rows, separated by lamellae of firm, white glialtissue. In the lateral parts of the white matter the lacunaewere larger and more widely spaced out than those situ-ated more medially. The cortex over the affected areasappeared normal. Right Ammon's horn was shrunkenand discoloured. Both lateral geniculate bodies wereatrophic. The intracranial portions of the optic nerves andthe optic chiasm showed no obvious lesions. The ventricleswere normal. No lesions were seen in the basal ganglia,brain-stem or cerebellum.The spinal cord externally appeared swollen and dis-

coloured from the lower cervical to the lower thoracicsegments. Transverse sections showed central softeningwith partial peripheral preservation from C4 to C7.From C8 to T 1I the cord appeared completely necroticwith patches of haemorrhagic discolouration. The lowestthoracic and all lumbar segments were fairly well pre-served and showed central small patches of brownishdiscolouration. The anterior and posterior roots andthe posterior root ganglia appeared normal.

Microscopic The cerebral cortex showed good pre-servation of its cyto-architecture with the exception ofright Ammon's horn which showed a large defect inSommer's sector of the pyramidal layer. Sections stainedfor myelin showed partial demyelination of the cortex inareas adjacent to the lesions in the white matter. This wasmost striking in the calcarine fissure where only the tipsof the cuneus and the lingual gyrus remained fullymyelinated, while in the deeper part of the fissure therewas total loss of myelin both in the radial fibres and in

FIG. 1. Coronalsection throughboth occipital lobesshowing concentricarrangement ofrows of lacunae,particularly on theright.

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The nosological position of concei

the stria of Gennari (Fig. 2). There was a mild marginalgliosis throughout the occipital cortex and in addition astriking proliferation of large spider astrocytes in layerVI of the visual cortex in the floor of the calcarine fissure(Fig. 3).The distributions of lesions in the white matter cor-

responded accurately with the macroscopic appearances.The central white matter of the occipital lobes wascompletely devoid both of myelin sheaths and of axonsand consisted of rows of lacunae separated by glial septaof variable thickness (Figs. 4 and 5). Some of the septaseparating the lacunae of the same rows were very slenderand consisted of a blood vessel and a few glial fibres(Fig. 6). Others formed somewhat wider bridges of tissue,containing blood vessels, proliferated astrocytes, glialfibres, and phagocytic microglia. Similar appearanceswere seen in the broader septa separating the rows oflacunae from each other. This central area of lacunarrarefaction was surrounded by a zone of demyelinationwith partial preservation of axons, extending deeply intothe subcortical white matter and encroaching in placesupon the cortex as noted above. While axons werepresent in these demyelinated zones their density was lessthan normal and decreased rapidly towards the centralarea of cavitation. Astrocytic proliferation and fibrillarygliosis were prominent and phagocytic microgliaabundant. Many blood vessels were surrounded by thickcuffs of mononuclear cells, predominantly of microglialorigin. Similar appearances were observed in the spleniumof the corpus callosum and the adjacent white matter ofthe cingulate gyrus.The deep structures of the hemispheres were normal

with the exception of the lateral geniculate bodies, which

ntric lacunar leucoencephalopathy 133

showed severe atrophy with almost total loss of neurones.The optic pathway showed patchy demyelination in

the optic nerves and chiasm. The intra-orbital part of theright optic nerve showed total loss of myelin and severe,but not complete, loss of axons (Fig. 7). The nerveappeared very cellular owing to astrocytic and microglialproliferation. A dense network of fine glial fibrils waspresent throughout the nerve. The left optic nerveappeared slender, the cords of myelinated fibres werethinner than normal and the fibrous septa crowdedtogether (Fig. 8). Despite this appearance of mildatrophy the density of axons and their myelinationseemed normal and fibrillary gliosis minimal. The chiasmshowed massive demyelination of the decussation incontinuation with the plaque in the right optic nerve(Fig. 9). There was also a small irregular plaque at theleft lateral margin of the chiasm.

In the spinal cord the lesions became apparent at thelevel C4 where a central area of recent necrosis withbreakdown of axons and myelin sheaths occupied mainlythe deeper parts of the posterior columns (Fig. 10).Caudally, the lesion increased rapidly in size and at C8occupied almost the entire cross-section of the cord withthe exception of a thin peripheral rim of preservedmyelinated fibres (Fig. 11). Amid this massive breakdownof the white matter the grey matter appeared relativelywell preserved and the neurones of the anterior andposterior horns were apparently unaffected. The lesionreached its maximum intensity at T4 where destructionof the cord was total and apparently of longer durationthan in the cervical segments (Fig. 12). There was diffuseproliferation of phagocytic microglia and patchy in-filtration by polymorphonuclear leucocytes, but no

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FIG. 2. Right visual cortex: myelin is preserved only inthe tips of the gyri while the deeper parts are totallydemyelinated. Kluver and Barrera's luxol fast blue andcresyl violet, x 7.

FIG. 3. Right occipital cortex: proliferation of spiderastrocytes in floor of calcarinefissure adjacent to glial wallof medial row of lacunae. Holzer's method for glial fibres,x 150.



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FIG. 4. Section of right occipital lobe stained for myelin FIG. 5. Adjacent section stained for glial fibres: theshowing extent of demyelination and lacanar rarefaction. concentric arrangement of glial septa is clearly seen.Kluver-Barrera, x 1-8. Holzer, x 1-8.

FIG. 6. Rightoccipital lobe:groups of thin-walled lacunaeseparated by thickglial septum.Holzer, x 45.

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FIG. 7. Right optic nerve: total loss of myelin andincreased cellularity due to proliferation of glial cellsKIl ver-Barrera, x 30.

astrocytic reaction. Similar appearances were seen inlower segments of the thoracic cord down to T10, butwith gradual reappearance of small islands of myelinatedfibres. At T12 the necrosis was reduced to a central coreinvolving the base of the posterior columns. This con-tinued as a thin tail of circumscribed necrosis in the leftposterior column down to the level L5 (Fig. 13).

DISCUSSION

The clinical diagnosis in this case presented con-siderable difficulty. In retrospect, when the fullrecords were brought together from the five hospitalsin which the patient had been investigated, theevolution of the disease and the distribution of thelesions might have suggested a demyelinating dis-ease, possibly neu,romyelitis optica. The unusually

FIG. 8. Left optic nerve: preservation of slender cords ofmyelinatedfibres. Kliiver-Barrera, x 30.

advanced age should not have precluded thediagnosis, as the incidence of this disease coversa span from 5 to over 60 years (McAlpine, 1938).The clinicopathological concept of neuroptico-

myelitis is not entirely clear. The clinical picture wasfully reviewed by Stansbury (1949) on a materialconsisting of 200 reported cases. The syndromeconsists of blindness, temporary or permanent,followed after a variable, though usually short,interval by paraplegia of rapid onset. The disease isprogressive and often rapidly fatal, but cases runninga remitting and relapsing course have been reported.Pathologically the lesions fall into three groups(Greenfield and Norman, 1963): some are examplesof multiple sclerosis involving predominantly theoptic pathways and the spinal cord, others resemble

FIG. 9. Optic chiasm: plaque of demyelinationextendingfrom right optic nerve into decussation;also small plaque at base of left optic nerve.Kliiver-Barrera, x 7.

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FIG. 10. Spinal cord, segment C4: central area ofnecrosis,affecting mainly ventral two thirds of posterior columns.Kliiver-Barrera, x 7.

acute perivenous encephalomyelitis of similar dis-tribution, others still consist of demyelinating lesionsin the optic pathways associated with acute necroticmyelopathy. Hughes (1966) suggested that only thelast group formed a separate entity for which theterm neuromyelitis optica should be retained.The association of necrotizing myelopathy, in-

distinguishable from the isolated myelomalaciadescribed originally by Bassoe and Hassin (1921)and fully reviewed by Hughes (1961), with asym-metrical plaques of demyelination in the optic nervesclearly places our case in this last group. Theunusual findingwas the lesion affecting both occipitallobes and the splenium of the corpus callosum andclosely resembling the concentric lacunar leuco-encephalopathy of Grcevic (1960). Demyelinatinglesions in the occipital lobes have been reported in

FI. 11. Spinal cord, segment C8: almost total necrosiswith partial preservation of thin peripheral rim of myelin.Kliiver-Barrera, x 7.

FIG. 12 Spinal cord segment T massive necrosis ofcord; dark areas represent leucocytic infiltration, notpreservation of myelin. Klver Barrera x 7.

several cases of Devic's disease (Marinesco, Drag-anesco, Sager, and Grigoresco, 1930; Greenfield,1950; Paarmann, 1952). The case of Marinescoet al. is of particular interest in that the extensive,though strictly unilateral, parieto-occipital lesionconsisted of an outer demyelinated and inner lacunarzone. The lacunae, however, were not arrangedconcentrically, and the intervening tissue containeddemyelinated axons as well as glial fibres. Thesignificance of the concentric pattern and its possiblerelationship to the 'encephalitis periaxialis con-centrica' of Balo (1928) was fully discussed byGrcevih and our case throws no new light on this

FIG. 13. Spinal cord, segment L5: small circumscribedarea of necrosis in one posterior column. Klii'ver-Barrera,x 7.

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The nosological position of concentric lacunar leucoencephalopathy

problem. The essential difference between lacunarencephalopathy and Balo's sclerosis lies in the factthat in the latter zones of demyelination are separatedby lamellae of preserved white matter, in the lacunartype zones of cavitation alternate with glial septadevoid of axons and myelin sheaths.Our case differs from that of Grcevic mainly in

the distribution of the lesions which in his affectedthe frontal lobes and the anterior third of the corpuscallosum. The optic nerves and spinal cord were notexamined. While there was no clinical suggestion ofa myelopathy the history of recurrent episodes ofloss of vision progressing towards almost totalblindness suggested involvement of the optic path-ways presumably by a demyelinating process.Nevertheless Grcevic considered that the availableevidence did not warrant the inclusion of his case inany definite nosological group.We feel that our case clarifies the nosological

position of concentric lacunar leucoencephalopathy.The association with typical neuropticomyelitisplaces this lesion within the context of de-myelinating diseases.

SUMMARY

A man aged 64 presented with left homonymoushemianopia rapidly progressing to total corticalblindness. This was followed by a transient lefthemiparesis and grand mal seizures. Fourteenmonths later he developed a rapidly progressiveascending myelopathy to which he succumbed.Post-mortem examination of the nervous systemrevealed plaques of demyelination in the optic

nerves and chiasm, an acute necrotizing myelopathy,and bilateral lesions in the occipital white matteridentical with those described by Grcevi6 under thename of concentric lacunar leucoencephalopathy.The association of this condition with typical neur-opticomyelitis suggests its close relationship to thedemyelinating diseases.

We are indebted for the excellent documentation of thiscase, and for permission to publish it, to Dr. R. A.Henson and Mr. T. T. King, and also to Dr. F. Lees,Mr. B. Fairburn, and Lt. Col. A. V. Forage.

REFERENCES

Bal6, J. (1928). Encephalitis periaxialis concentrica. Arch. Neurol.Psychiat. (Chic.), 19, 242-264.

Bassoe, P., and Hassin, G. B. (1921). Myelitis and myelomalacia: aclinico-pathologic study with remarks on the fate of gittercells. Arch. Neurol. Psychiat. (Chic.), 6, 32-43.

Grcevic, N. (1960). Concentric lacunar leukoencephalopathy. Arch.Neurol. (Chic.), 2, 266-273.

Greenfield, J. G. (1950). The classification of diffuse demyelinatingsclerosis of the brain on the basis of pathogenesis. Foliapsychiat. neeri., 53, 255-267.and Norman, R. M. (1963). Neuropticomyelitis (neuromyelitisoptica, Devic's syndrome), in Greenfield's Neuropathology,pp. 496-499, 2nd edition. Edited by W. Blackwood, W. H.McMenemey, A. Meyer, and D. S. Russell. Arnold: London.

Hughes, J. T. (1961). Acute Idiopathic Myelomalacia. MD Thesis,Victoria University: Manchester.

(1966). Pathology of the Spinal Cord. Pp. 150-152. Lloyd-Luke:London.

McAlpine, D. (1938). Familial neuromyelitis optica: its occurrence inidentical twins. Brain, 61, 430-448.

Marinesco, G., Draganesco, S., Sager, O., and Grigoresco, D. (1930).Sur une forme particuliere anatomo-clinique d'ophtalmo-neuromy6lite (Ophtalmo-ene6phalo-my6lite). Rev. neurol., 3,193-228.

Paarmann, H. F. (1952). Beitrag zur Neuromyelitis Optica. Dtsch. Z.Nervenheilk., 168, 384-400.

Stansbury, F. C. (1949). Neuromyelitis optica (Devic's disease):presentation of 5 cases, with pathologic study, and review ofliterature. Arch. Ophthal., 42, 292-335, and 465-501.

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