A case of cerebral hypoplasia/dysplasia detected at autopsy


Nekroptický případ hypoplázie/dysplázie mozku

I když existují pouze omezené údaje o frekvenci výskytu vývojových malformací mozkové kůry, jedná se o významné příčiny mentální retardace, epilepsie a dalších neurologických postižení. Vzhledem k sofistikovaným neuroradiologickým metodám jsou detekovány častěji než dříve. I když jejich příčina není úplně známa, zdá se, že se jedná o odezvu mozku na genetické faktory a vliv prostředí. Je známo, že faktory prostředí mohou v těhotenství ovlivňovat migraci neuroblastů a rovněž je znám i genetický původ mnoha poruch neuronální migrace. Epilepsie, psychomotorická retardace a ložiskové neurologické postižení patří rovněž mezi významné klinické symptomy. Epileptické ataky mohou být lokalizované či generalizované. V našem případě se jednalo o dívku ve věku dvou let, která byla dle údajů rodiny léčena po dobu téměř jednoho roku s diagnózou multifokální epileptiformní anomálie. Postupně u ní docházelo k omezení hybnosti a ke konci již stěží udržela hlavu ve vzpřímené poloze. Často též trpěla záchvaty křečí a chyběla aktivní hybnost dolní poloviny těla. Byla nalezena bez známek života dopoledne se své posteli, přičemž byla nařízena pitva ke zjištění přesné příčiny smrti. Pitva byla provedena na pracovišti v Burse, Turecko, kdy při zevní prohlídce nebyly zjištěny žádné stopy násilí. Při vlastní pitvě bylo pozorováno ztenčení mozkových závitů v čelním a temenním laloku levé hemisféry, výrazné prohloubení mozkových rýh a celkově hypoplastický vzhled mozku. Histologickým vyšetřením byla zjištěna pneumonie, v mozkové tkáni mikrogyrální formace, narušená stratifikace kory, hypercelularita, změny stavby neuronálních struktur a balónové buňky při obrazu kortikální dysplazie. Bezprostřední příčina smrti u dítěte s kongenitální multifokální epileptiformní anomálií byla stanovena jako pneumonie. Naším cílem bylo prezentovat případ hypoplazie mozku, který je i s ohledem na literaturu v pitevním materiálu zřídka vídaným jevem.

Klíčová slova:
hypoplázie/dysplázie mozku – pitva – vrozené malformace – náhlé úmrtí.


Authors: Nursel Türkmen İnanir1,2;  Filiz Eren2;  Mustafa Numan Ural1;  Bülent Eren2;  Murat Serdar Gürses1
Authors place of work: Uludağ University Medical Faculty, Forensic Medicine Department, Bursa, Turkey.1;  Council of Forensic Medicine of Turkey, Bursa Morgue Department, Bursa, Turkey.2
Published in the journal: Soud Lék., 60, 2015, No. 1, p. 4-6
Category: Kazuistika

Summary

Presented case was a 2–year-old baby girl who had been treated for nearly one year with the indication of multifocal epileptiform anomaly. She was found dead in her bed in morning hours, autopsy was planned after prosecutors investigation. On internal autopsy examination, shrinkage of gyral structures in the frontal, and parietal lobes of the left hemisphere, markedly enlarged sulci, and a hypoplastic appearance were noted. Histopathological examination revealed evidence of pneumonia, brain exposed microgyral formations, disordered cortical stratification, hypercellularity, dysmorphic neuronal structures, balloon cells with diagnosis of cortical dysplasia. Pneumonia was reported as a cause of death. We aimed to discuss in the light of the literature a case with cerebral hypoplasia which is rarely seen at forensic autopsies.

Keywords:
cerebral hypoplasia/dysplasia – autopsy – congenital malformation – sudden death.


Though limited information is available about the cortical developmental malformation, these types of malformations are known to be among important causes of mental-motor retardation, epilepsy, and other neurological disorders. Owing to sophisticated neuroradiological methods, it is more frequently detected (1-8). Although its underlying pathological etiologies are not completely known, it has been evaluated as a cerebral response to genetic, and environmental factors. Besides many factors in pregnancy are known to effect migration of neuroblasts, and genetic origins of many neuronal migration disorders have been also indicated in the literature (1-3).

CASE REPORT

As we learnt from her family, our case was a 2 –year-old baby girl who had been treated for nearly one year with the indication of multifocal epileptiform anomaly, and his physical activity slowed down with age, and she could hardly hold her head at erect position. Besides she couldn’t move her lower part of her body by herself , and suffered from frequent convulsive seizures. Her family was a housekeeper of a farmhouse, and she was found dead in her bed in the morning hours by her grandmother. The prosecutor requested autopsy to determine the precise cause of her death. On her autopsy, external physical examination of the corpse performed in Bursa Morgue Department could not reveal any traumatic lesion except for an ecchymotic area on the lateral part, and upper eyelid of her right eye of this baby girl who was 90 cm in height, and 10 kg in weight. On internal examination, her brain (569 gr), heart (76 gr), right lung (134 gr), left lungs (120 gr), and liver (569 gr) were weighed. On cerebral dissection, macroscopic differences were detected between cerebral hemispheres. Shrinkage of gyral structures in the frontal, and parietal lobes of the left hemisphere, markedly enlarged sulci, and a hypoplastic appearance relative to the contralateral hemisphere were observed (Fig. 1). In the same region, markedly enlarged meningeal capillaries, and congestion were detected. Mottled appearance of the lungs, signs of congestion in the heart, and kidneys, and fatty liver were also observed. On histopathological examination, microgyral formations, increase in the number of   meningeal capillaries, disordered cortical stratification, hypercellularity, dysmorphic neuronal structures, balloon cells, and cortical dysplasia were detected (Fig. 2). Mottled appearance of the lungs, infiltration of neutrophilic leukocytes within alveoli, and brochial lumens, signs of edema, congestion, and pneumonia were detected. Chemical analyses revealed the presence of therapeutic doses of antiinflammatory paracetamol (126 ng/mL), and antiepileptic valproic acid (2526 ng/mL) in blood which were excreted in urine. On systematic biochemical analyses, any other toxic material was not detected in blood, and urine samples. Cause of death of this baby with the diagnosis of congenital multifocal epileptiform anomaly was reported as pneumonia. Herein, we intended to discuss hypoplastic-dysplastic cerebral anomaly which is rarely seen in forrensic autopsies in the light of the literature findings.

Fig. 1. Macroscopic view: A hypoplastic appearance of frontal, and parietal lobes of the left cerebral hemispheres.
Fig. 1. Macroscopic view: A hypoplastic appearance of frontal, and parietal lobes of the left cerebral hemispheres.

Fig. 2. Disordered cortical stratification of the brain, hypercellularity, and proliferation of meningeal capillaries (HE 40x).
Fig. 2. Disordered cortical stratification of the brain, hypercellularity, and proliferation of meningeal capillaries (HE 40x).

DISCUSSION

Though limited information is available about the frequency, and causes of cortical developmental malformations of the brain , these types of malformations are among important causes of mental-motor retardation, epilepsy, and other neurological disorders (1-8). Epilepsy, motor- mental retardation, and focal neurological problems are the most important clinical presentations as is in our case. Besides epileptiform seizures with partial, and generalized attacks have been reported (1-4). Similar to our case, Fauser et al.(5) emphasized that despite antiepileptic treatment, history of epileptiform seizures can be detected. They also indicated that in some cases these epileptic seizures can not become manifest   for years, and also demonstrate resistance against certain antiepileptic drugs which are predominantly seen in cases with cytoarchitectural abnormalitities. In the developmental anomalies of the brain, symptoms in a wide spectrum have been reported on macroscopic examinations, while some authors also indicated the presence of hypoplastic lesions, and asymmetries in cerebral lobes (1,2,3,6). Cortical dysplasias of the brain were firstly defined by Taylor, and Falconer in the early 1970s (6,7). Nowadays, as for neuropathological, and clinical features, non-Taylor-types of focal cortical dysplasia have architectural, and cytoarchitectural subtypes, while Taylor-type cortical dysplasia is categorized as subtypes with or without balloon cells.Generally three main subtypes of cortical dysplasia have been defined. In neuropathological classifications of cortical dysplasias, in the presence of dysplastic cytorarchitecture, cortical laminar disarrangement, dysmorphic neurons, and giant balloon cells have been detected (6,7). Microscopic examination of our case revealed microgyral formations, increase in meningeal capillaries, and also characteristic histopathological findings of cortical dysplasia including disordered cortical stratification, hypercellularity, balloon-type cells. Despite some attempts at categorization of cortical dysplasias based on the presence of certain microtubule-associated proteins, and genes effective on migration, irrefutable conclusions which might lead to detailed classification of cortical dysplasias have not been suggested up to now (3,8). It has been also emphasized that among radiological modalities, cerebral MR might reveal some characteristic differences between Taylor-, and non-Taylor type dysplasias which might also have a favourable effect on organization of preoperative planning. The researchers also underlined some potential differences between surgical treatments of Taylor, and non-Taylor type cortical dysplasias (7,8). Rapid advances in biological, and imaging techniques increase our knowledge about cerebral cortical dysplaisas (6). However, as is revealed in our case, necroptic examinations have proved that especially in pediatric cases histopathological analysis of cerebral specimens should be more carefully conducted, and also evidenced that autopsy examinations is helpful in detailed comprehension, and precise classification of cerebral malformations.

Correspondence address:

Bülent Eren, M.D.

Council of Forensic Medicine of Turkey

Bursa Morgue Department;16010, Bursa, Turkey.

tel.: +90 224 222 03 47; fax: +090 224 225 51 70

e-mail: drbulenteren@gmail.com


Zdroje

1. Whiting S, Duchowny M. Clinical spectrum of cortical dysplasia in childhood: diagnosis and treatment issues. J Child Neurol 1999; 14: 759-771.

2. Hayward JC, Titelbaum DS, Claney RR, Zimmerman RA. Lissencephaly-pachygyria associated with congenital cytomegalovirus infection. J Child Neurol 1991; 6: 109-114.

3. Barth PG. Disorders of neuronal migration. Can J Neurol Sci 1987; 14: 1-16.

4. Koehn MA, Duchowny M. Preoperative Clinical evaluation and noninvasive electroencephalogram in cortical dysplasia. Neurosurg Clin N Am 2002; 37: 35-39.

5. Fauser S, Huppertz HJ, Bast T, et al. Clinical characteristics in focal cortical dysplasia: a retrospective evaluation in a series of 120patients. Brain 2006; 129(Pt 7): 1907-1916.

6. Barkovich AJ, Guerrini R, Kuzniecky RI, Jackson GD, Dobyns WB. A developmental and genetic classification for malformations of cortical development: update2012. Brain ;135(Pt 5): 1348-1369.

7. Colombo N, Tassi L, Galli C, et al. Focal cortical dysplasias: MR imaging, histopathologic, and Clinical correlations in surgically treated patients with epilepsy. Am J Neuroradiol 2003; 24: 724-733.

8. Guerrini R, Dobyns WB, Barkovich AJ. Abnormal development of the human cerebral cortex: genetics, functional consequences and treatment options. Trends Neurosci 2008; 31(3): 154-162.

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