Diagnosis of neuronal ceroid lipofuscinosis in forensic medical practice

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Introduction. Neuronal ceroid lipofuscinosis (NCL) is a group of genetic diseases that occur due to the abnormal accumulation of lipofuscin–like substances in the cellular structures of mainly neurons. This pathology is controlled by recessive alleles of the autosomal gene. To date, there are 14 known different forms of NCL. In the world, this pathology occurs with a frequency of 1 in 25,000, which is a fairly high indicator [2].The pathogenesis of NCL development is poorly understood today, however, it is known that this pathology belongs to the group of metabolic diseases. The pathological metabolism of lysosomal enzymes leads to the accumulation of lipofuscin-like substances in the tissues of the nervous system, which leads to the death of neurons, and as a result, the corresponding clinical picture of the disease [1, 2].NCL is characterized by a predominant lesion of the central nervous system with the development of disorders of various spectra, including intellectual and motor, as well as progressive myoclonusepilepsy and damage to the organ of vision. Sleep disorders and mental disorders may also be associated with these symptoms. The life expectancy of patients with this pathology is about 5 years after the first symptoms of the disease [3]. It is important to note that the clinical picture of this disease is significantly similar to other hereditary metabolic diseases, which in many ways causes difficulties in diagnosing NCL [3].Postmortem forensic diagnosis of NCL is an urgent problem, as this topic is only highlighted in a few publications in modern scientific literature.The aim of the work is to identify diagnostically significant morphological changes in the internal organs of a 6–year-old child at death from CNL based on a comprehensive forensic medical examination.Materials and methods of research. In the course of this study, the accompanying documents (the decision on the appointment of an expert examination, the protocol of examination of the corpse at the scene), medical documents confirming the child's diagnosis, and a sectional examination of the corpse with microscopic examination of autopsy preparations stained with hematoxylin and eosin, sudan III were analyzed.The results of the study. The analysis of medical documentation made it possible to establish the presence of CNL in a child diagnosed during his lifetime, and also made it possible to determine the clinical picture corresponding to this pathology: there was a delay in psychomotor development, ataxia, visual impairment, loss of previously acquired skills, myoclonic twitching, dementia and spastic tetraparesis also developed. Death occurred at the age of 6 years from the progression of the disease. An important step in determining the cause of death is the analysis of medical documentation, which in turn confirms the presence of CNL in the child during his lifetime, and reflects the corresponding clinical picture and the history of progression of the pathological condition.During the sectional examination of the corpse, we identified several diagnostically significant signs. It is important to note that the thickness of the skull bones in children of this age group normally does not exceed 1-1.5 cm, however, in this forensic medical case, the thickness of the bones of the child's skull was 2 cm. Since CNL is a neurodegenerative disease, it is of great interest to study the brain, which subsequently also revealed pathological changes. It was found that the brain occupies 2/3 of the cranial cavity, due to atrophy of the cerebellar cortex and the major hemispheres. It also revealed areas of destruction with pronounced swelling of the brain matter and soft meninges.Histological examination of the brain shows atrophy of the brain substance with destructive changes in the nerve cells of macroglia and oligodendroglia, a sharp rounding of their contours ("granular" balls"), swelling, and the presence of "pulverized" brown inclusions in almost all nerve cells (Figure 1).In the differential diagnosis of this pathology, the use of staining of histological preparations with Sudan Sh is particularly important., since this azo dye allows you to identify important signs, namely: lipid inclusions perivascularly and in the walls of individual vessels of the brain substance (Figure 2). Pronounced perifocal edema was also noted during the examination of microscopic brain preparations. Diffuse dystrophic changes were noted in the study of other organs, however, the main diagnostically important criteria for determining the diagnosis and cause of death are pathological changes in the nervous tissues. A comprehensive analysis of macroscopic changes, as well as changes detected during histological examination, makes it possible to accurately diagnose a child with CNL.Conclusion. This example from forensic medical practice clearly demonstrates the complexity and large amount of work with these cases, as well as the importance of applying an integrated approach to determining the cause of death. In the course of a comprehensive analysis, it is important to take into account medical documentation, as well as the results of autopsy and histological examination using a specific histochemical staining technique for detecting lipids (sudan III), which allows for differential diagnosis with other neurodegenerative and metabolic pathologies and accurately determine the cause of death.

About the authors

Sofia Dmitrievna Vasilyeva

Tver State Medical University

Email: high.cat.003@gmail.com
ORCID iD: 0009-0009-9307-9910
SPIN-code: 6829-4920
Russian Federation, 4 Sovetskaya street, 170100, Tver, Russian Federation

Olga Ivanovna Kolesnik

Tver State Medical University

Email: o.i.kolesnik@mail.ru
SPIN-code: 4449-4392
Russian Federation, 4 Sovetskaya street, 170100, Tver, Russian Federation

Anna Aleksandrovna Bibikova

Tver State Medical University

Author for correspondence.
Email: bibikovaaa@mail.ru
ORCID iD: 0000-0002-4130-2756
SPIN-code: 6856-2168
Russian Federation, 4 Sovetskaya street, 170100, Tver, Russian Federation

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