Introduction
Here we attempt to rescue from obscurity the report of a case of probable subcortical band heterotopia, also known as subcortical laminar heterotopia, which was published in the English medical literature in the first decade of the twentieth century by the neuropathologist Helen Gertrude Stewart (1874-1959) [1].
Having graduated from the University of Birmingham in 1905, Helen Stewart worked at the pathological laboratory of Claybury Asylum, the laboratory of the London County Asylums. Here she undertook post-mortem studies which formed the basis of her MD thesis Notes and observations on forty consecutive cases of new growth. Examined in the Pathological Laboratory of the London County Asylums at Claybury (held in the University of Birmingham Research Reserve). The thesis was supervised by Frederick Walker Mott (1853-1926), the Director of the Claybury Asylum pathological laboratory, and the MD degree was conferred by Birmingham University in 1908 [2].
The case we revisit, which was not part of her thesis work, was published in the journal of London County Asylums, the Archives of Neurology and Psychiatry from the Pathological Laboratory of the London County Asylums, edited by Mott, now a long defunct journal (it can be viewed on Internet Archive).
Case Report
The patient reported by Helen Stewart was diagnosed as an “epileptic imbecile”, the now unacceptable terminology of the times used to describe an individual with learning disability and epileptic seizures. This patient had been in the custodial system of workhouse and then asylum from the age of 11, having developed seizures at age eight on the background of delayed development, not walking until she was three. Her speech was described as “childish”. She died aged 37 from pulmonary tuberculosis, a disease commonly encountered in asylum patients.
Pathology
Both macroscopic and microscopic examination of the brain was performed, according to the standards of the day. Macroscopically the sulci were judged shallow and the Sylvian fissures slanted obliquely upwards (Figure 1). On section of the cortex to examine the internal structure, a striking observation was made:
the cortex was found to be only slightly narrower than normal, but beneath the cortical grey matter throughout the whole cerebrum, with the exception of the fornicate and hippocampal gyri, was a deep grey band.
The thickness of this subcortical layer was measured and found to have a much greater depth than that of the cortex.
For microscopical examination, the brain was stained using Nissl’s method for nerve cells and the Kulschitski-Pal method for fibres.
On microscopical examination this band [beneath the cortical grey matter] proved to be a second deep layer of nerve cells, which was separated from the cortex by a well-defined streak of white matter.
The cells in the sub-cortical layer were irregular in arrangement and distribution. As before stated, this layer was not visible to the naked eye as a grey area in the hippocampal or callosal gyri, but well-formed isolated cells were scattered between the fibres in these situations also. This layer formed a continuous deep belt of cells, but the lower edge of the belt was broken up into islands by bands of fibres.
No definite layers were discernible in this sub-cortical zone of cells. The cells lie at all angles, but a general view with the low power shows that there is a tendency on the whole for the apical process to point towards the cortex and the base inwards. The pyramidal type of cell predominates, but many polymorphic and immature cells are present.
The cells and fibres were drawn by means of a camera lucida and compared with a normal adult brain and an infant brain to illustrate the embryonic or infantile nature of the cells and the small calibre of fibres resembling the defectively myelinated fibres of a developing brain. A slight excess of neuroglial nuclei was also noted.
Formulation
Accepting the epistemic limitations necessarily applicable to attempted retrospective diagnosis, we submit that Helen Stewart’s case is suggestive of the diagnosis of subcortical band (or laminar) heterotopia. This is an X-linked recessive condition occurring mostly in females and characterised by a severe seizure disorder beginning in childhood, often in association with learning disability, the phenotype reported in Stewart’s patient. Microscopically the brain in these patients manifests a subcortical grey matter band which is lacking in lamination and consists of disoriented neurones, both features observed histologically by Stewart. The lack of lamination invalidates use of the term “double cortex” sometimes applied to this condition, although this persists in the name of the aberrant gene, Doublecortin (DCX).
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Discussion
The advent of MR brain imaging in the late 1980s and early 1990s revolutionised the diagnosis of neuronal migration disorders as a cause of epilepsy due to the observation of characteristic neuroradiological signatures of laminar and nodular forms of heterotopia, including subcortical band heterotopia [3]. Prior to this, neuronal migration disorders had been categorised on clinico-pathological grounds [4], the earliest pathological descriptions dating from the latter half of the nineteenth century, mostly in the German literature. Stewart cited Rudolf Virchow (1820-1902) as defining “heterotopia of the cortex as grey matter occurring in positions normally occupied by other structures”, a definition dating to 1867 [5]. Only a handful of cases of heterotopia were discovered by Stewart in her literature review, many of the nodular type (“isolated areas of cells in the neighbourhood of the ventricular walls”), presumably what would now be called subependymal nodular heterotopia. However, the case reported by Magnus Matell, from Professor Wernicke’s psychiatric clinic in Breslau [6], “gives a full account of a female epileptic imbecile dying at the age of 25 years who, both in history and cerebral conformation closely resembles the case we have described. Not only does the subcortical layer of cells occupy very much the same extent and position, but Matell notes a deficiency in pyramidal cells of the superficial cortex, and mentions that the polymorphic layer is continued down into the subcortical medullary substance”.
Stewart concluded her paper with the following, prescient comment:
It is, I think, clear that this case should be put in a different category from those in which isolated areas appear in the walls of the ventricle; the occurrence of the latter in otherwise normal brains shows that, though they may be developmental anomalies, possibly reduplication of lenticular, caudate, or amygdaloid nuclei, which we know to be of similar origin to the cortex, there may be no marked under-development of neurons [sic] in these cases and they are not necessarily accompanied by epilepsy or deficient mental capacity.
The differentiation between nodular and laminar forms of heterotopia is usually ascribed to a paper of 1936 by Hans Jacob working in Munich [7], but it is clear from this quotation that Stewart pre-empted him by more than a quarter of a century in recognising the possible differences in the clinical correlates of these forms of heterotopia. The relative obscurity of the journal in which Helen Stewart had published her case probably ensured that it was unknown to Jacob; certainly he did not reference it.
The clarity of Stewart’s presentation and exposition prompts us to argue that her paper merits greater attention as a noteworthy contribution in the history of neuronal migration disorders.
References
- Stewart HG. A description of the brain of an epileptic imbecile showing extensive heterotopia of the grey matter. Archives of Neurology and Psychiatry from the Pathological Laboratory of the London County Asylums 1909; 4: 289-296.
- Maguire M, Larner AJ. Helen Gertrude Leyton (1874-1959). Journal of Neurology. 2026;273:401. https://doi.org/101007/s00415-026-13944-5
- Barkovich AJ, Jackson DE Jr. Boyer RS. Band heterotopia: a newly recognized migration anomaly. Radiology 1989; 171 :455-458. https://doi.org/10.1148/radiology.171.2.2468173
- Barth PG. Disorders of neuronal migration. Canadian Journal of Neurological Sciences 1987; 14: 1-16.
https://doi.org/10.1017/S031716710002610X - Virchow R. Heterotopie der grauen Hirnsubstanz [Heterotopia of the grey matter of the brain]. Archiv für pathologische Anatomie und Physiologie und für klinische Medicin 1867; 38: 138-142.
https://doi.org/10.1515/9783112390740-007 - Matell M. Ein Fall von Heterotopie der grauen Hirnsubstanz in den beiden Hemisphären des Grosshirns. Archiv für Psychiatrie und Nervenkrankheiten 1893; 25: 124-136. https://doi.org/10.1007/BF02679116
- Jacob H. Faktoren bei der Entstehung der normalen und der entwicklungsgestörten Hirnrinde [Factors in the development of the normal and developmentally disturbed cerebral cortex]. Zeitschrift für die gesamte Neurologie und Psychiatrie 1936; 155: 1-39. https://doi.org/10.1007/BF02865566
