Bilateral neuropathologic changes in a child with hemimegalencephaly

doi:10.1016/S0887-8994(97)00091-X

Pediatric Neurology

Volume 17, Issue 4, November 1997, Pages 344-349

https://doi.org/10.1016/S0887-8994(97)00091-X Get rights and content

Abstract

Evaluation of a 7-month-old girl with developmental delay and intractable seizures revealed hemispheric asymmetry and an enlarged right cerebral hemisphere. Because of a history of seizures refractory to medical therapy, she was admitted for right hemispherectomy, but died of complications of surgery. Postmortem brain examination revealed asymmetric enlargement of the right cerebral hemisphere but no gross abnormalities in the left hemisphere. Microscopic examination demonstrated bilateral neuropathologic changes consistent with severe cortical dysplasia in the right cerebral hemisphere and mild cortical dysplasia in the left. Although white matter abnormalities in the unaffected hemisphere have been reported in hemimegalencephaly, bilateral cortical abnormalities, not reported previously in patients with hemimegalencephaly, may account for the varied clinical outcome with medical therapy or after hemispherectomy.

References (41)

P. Rakic
Defects of neuronal migration and the pathogenesis of cortical malformations
Prog Brain Res
(1988)
R. Sakuta et al.
Epidermal nevus syndrome with hemimegalencephaly: Neuropathological study
Brain Dev
(1991)
F. Van Huizen et al.
Indications for a critical period of synapse elimination in developing rat cerebral cortex cultures
Dev Brain Res
(1987)
M.P. Mattson
Neurotransmitters in the regulation of neuronal cytoarchitecture
Brain Res Rev
(1988)
V.H. Perry et al.
Dendritic competition: Competition for what?
Dev Brain Res
(1988)
F.H. Gage et al.
NGF-receptor reexpression and NGF-media adminolergenic neuronal heypertrophy in the imaged adult neosmatum
Neuron
(1989)
A.J. Barkovich et al.
Unilateral megalencephaly: Correlation of MR imaging and pathologic characteristics
AJNR
(1990)
A.J. Barkovich et al.
MR of neuronal migration anomalies
AJNR
(1987)
O. Robain et al.
Hemimegalencephaly: A clinicopathological study of four cases
Neuropathol Appl Neurobiol
(1988)
J.Q. Trounce et al.
Hemimegalencephaly: Diagnosis and treatment
Dev Med Child Neurol
(1991)

J.M. Taha et al.

The role of hemispherectomy in the treatment of holohemispheric hemimegalencephaly

J Neurosurg

(1994)

A. Palmini et al.

Operative strategies for patients with cortical dysplastic lesions and intractable epilepsy

Epilepsia

(1994)

F. Andermann et al.

Surgically remedial diffuse hemispheric syndromes

P.S. Mischel et al.

Cerebral cortical dysplasia associated with pediatric epilepsy. Review of neuropathologic features and proposal for a grading system

J Neuropathol Exp Neurol

(1995)

M.A. Farrell et al.

Neuropathologic findings in cortical resections (including hemispherectomies) performed for the treatment of intractable childhood epilepsy

Acta Neuropathol

(1992)

L. Pavone et al.

Epidermal nevus syndrome: A neurologic variant with hemimegalencephaly, gyral malformation, mental retardation, seizures, and facial hemihypertrophy

Neurology

(1991)

R. Cusmai et al.

Hemimegalencephaly and neurofibromatosis

Neuropediatrics

(1990)

P.A. Battistella et al.

Hypomelanosis of Ito and hemimegalencephaly

Clin Nerv Syst

(1990)

H.V. Vinters et al.

The neuropathology of human symptomatic epilepsy

M.J. De Rosa et al.

Neuropathologic findings in surgically treated hemimegalencephaly: Immunohistochemical, morphometric, and ultrastructural study

Acta Neuropathol

(1992)

Cited by (56)

Epileptic children with hemispheres’ asymmetry. Quantitative brain magnetic resonance-based analysis of apparently unaffected hemisphere. Case-control study
2021, Epilepsy Research
Citation Excerpt :
HME group is composite and Hme classification is even more puzzling (Abdel Razek et al., 2009); however both disorders share the clinical presentation that is intractable epilepsy, mental retardation and neurological deficits correspondent to affected hemisphere (Santos et al., 2014). In both HME and Hme, the contralateral, apparently unaffected hemisphere, might appear normal on qualitative MRI investigation (Jahan et al., 1997; Salamon et al., 2006) but some previous quantitative studies in children with HME reported subtle alterations also in the contralateral and apparently normal hemisphere (Salamon et al., 2006; Mathern et al., 2007). Quantitative approach may overcome the shortcomings of qualitative radiological assessment which may be biased and inaccurate (Salamon et al., 2006; Walker et al., 2011) allowing a better definition and comparison of cortical and subcortical structures of both hemispheres.
We performed a quantitative hemispheres analysis in epileptic children with hemispheres’ asymmetry -due to unilateral dysplastic malformation- in order to recognize subtle volumetric changes of the contralateral and apparently unaffected hemisphere.
13 children with Hemimegalencephaly (HME) and 20 with Hemimicrencephaly (Hme) were clustered in subgroups according to underlying hemispheric cortical dysplastic malformation and epilepsy pattern. 3D FSPGR T1weighted images were used to assess white and grey matter volumes for both hemispheres. Each volumetric parameter was compared with the average of an age-matched healthy control group.
HME subgroups: HME with pachygyria and focal (HME-PG-F; n 6) or multifocal epilepsy (HME-PG-MF; n.7). In both subgroups affected hemisphere (AH) volume was increased and contralateral hemisphere (CH) showed white matter volume reduction; in HME-PG-MF grey matter volume of CH was more reduced than HME-PG-F.
Hme subgroups: Hme with polimicrogyria and focal epilepsy (Hme-PMG-F; n.8), Hme with giant subcortical nodular heterotopia and focal (Hme-SCH-F; n.6) or multifocal epilepsy (Hme-SCH-MF; n.6). In all subgroups AH volume was reduced; the volume of CH was significantly increased in Hme-PMG-F and Hme-SCH-MF while it was not significantly increased in Hme-SCH-F compared to affected hemisphere.
In patients with hemispheres’ asymmetry, quantitative high-resolution MRI offers a more objective assessment of brain structures volume. The type of hemispheric dysplastic malformation together with the age of epilepsy onset and epileptic pattern may contribute to changes in contralateral and apparently unaffected hemisphere. Future studies are warranted to evaluate whether the early identification of these changes might help in planning future antiepileptic treatments.
Neuronal Proliferation
2018, Volpe's Neurology of the Newborn
The awesome complexity of the human brain begins its evolution after the essential external form is established by the events described in Chapters 1 and 2. The events that follow are proliferation of the brain's total complement of neurons, estimated at 86 billion, the migration of these neurons to specific sites throughout the central nervous system, the series of organizational events that result in the brain's characteristically intricate circuitry, and finally the ensheathment of this circuitry with myelin, its neuron-specific membrane. These events span a period from the second month of gestation to adult life, including the perinatal period. Aberrations of brain development may be an important consequence of genetic perturbations as well as a variety of prenatal and perinatal insults at critical times during development. This chapter reviews the normal aspects of neuronal proliferation and discusses disorders encountered when normal development goes awry.
Long-term developmental outcome after early hemispherotomy for hemimegalencephaly in infants with epileptic encephalopathy
2013, Epilepsy and Behavior
Citation Excerpt :
Some authors support the hypothesis that HME involves the entire brain but is significantly more evident on one side on the basis of clinical features [18], neurophysiological observations [22], and functional neuroimaging findings [23]. Seemingly normal contralateral hemispheres on brain MRI may show evidence of dysplasia upon histological examination [20,24]. This theory is supported by the observation that 3 of our recurrent cases had systematic neurocutaneous syndromes, indicating that the contralateral hemisphere was potentially affected.
This study aimed to identify the effect of early hemispherotomy on development in a consecutive series of 12 infants with hemimegalencephaly (HME) demonstrating epileptic encephalopathy. Mean age at onset was 20.4 days (range, 1–140), mean age at surgery was 4.3 months (range, 2–9), and mean follow-up time was 78.8 months (range, 36–121). Eleven patients had a history of early infantile epileptic encephalopathy. Vertical parasagittal hemispherotomy was performed without mortality or severe morbidities. At follow-up, seizure freedom was obtained in 8 patients (66.7%), who showed significantly higher postoperative developmental quotient (DQ) (mean, 31.3; range, 7–61) than those with seizures (mean, 5.5; range, 3–8) (p = 0.02). Within the seizure-free group, postoperative DQ correlated with preoperative seizure duration (r = − 0.811, p = 0.01). Our results showed that shorter seizure duration during early infancy could provide better postoperative DQ in infants with HME and epileptic encephalopathy.
Etiology-specific differences in motor function after hemispherectomy
2013, Epilepsy Research
Citation Excerpt :
This could be explained by the bilateral character of the underlying pathology in patients with developmental etiologies, which also disturbs the structural and functional integrity of the remaining “healthy” hemisphere. Indeed, both structural (Jahan, 1997; Salamon et al., 2006) and functional contralateral abnormalities have been reported previously in hemimegalencephaly (Soufflet et al., 2004; Salamon et al., 2006), the pathology that constitutes more than half of our developmental etiology group. It has previously been shown that higher motor scores after hemispherectomy were correlated with higher scores on language and cognitive developmental tests (Jonas, 2004).
Prediction of functional motor outcome after hemispherectomy is difficult due to the heterogeneity of motor outcomes observed. We hypothesize that this might be related to differences in plasticity during the onset of the underlying epileptogenic disorder or lesion and try to identify predictors of motor outcome after hemispherectomy. Thirty-five children with different etiologies (developmental, stable acquired or progressive) underwent functional hemispherectomy and motor function assessment before hemispherectomy and 24 months after hemispherectomy. Preoperatively, children with developmental etiologies performed better in terms of distal arm strength and hand function, but not on gross motor function tests. Postoperatively, the three etiology groups performed equally poor in muscle strength and hand function, but gross motor function improved in those with acquired and progressive etiologies. Loss of voluntary hand function and distal arm strength after surgery was associated with etiology, intact insular cortex and intact structural integrity of the ipsilesional corticospinal tract on presurgical MRI scans. In conclusion, postoperative motor function can be predicted more precisely based on etiology and on preoperative MRI. Children with developmental etiology more often lose distal arm strength and hand function and show less improvement in gross motor function, compared to those with acquired pathology.
Unique discrepancy between cerebral blood flow and glucose metabolism in hemimegalencephaly
2010, Epilepsy Research
Citation Excerpt :
Although most of the patients who were treated surgically had favorable outcomes in our series, the seizure frequency did not improve in Patient 2, who may have had bilateral cortical dysplasia, since the 18FDG-PET examination at 5 months of age (after the callosotomy) showed abnormal glucose metabolism on the non-affected side too. The existence of bilateral cortical dysplasia results in a poor surgical outcome (Jahan et al., 1997). Alternatively, the non-affected hemisphere may have been already impaired secondarily even in this patient who underwent a callosotomy as early as 2 months of age (Soufflet et al., 2004).
Hemimegalencephaly (HME) presents as severe refractory seizures and requires early surgical treatment to prevent progression to catastrophic epilepsy. Single-photon emission computed tomography (SPECT) and positron emission tomography (PET) are useful imaging techniques for the presurgical evaluation of patients with intractable epilepsy. However, the results in HME are variable and no study has compared SPECT and PET performed at around the same time. We performed SPECT and PET for nine patients with HME, which was defined as a whole or part of affected hemisphere enlargement (three males, six females; age range 0.5–20 years). The ictal and interictal states were determined based on the presence or absence of clinical seizures during all PET examinations and majority of SPECT examinations. The perfusion pattern in the malformed hemisphere was increased or equal, despite the reduced glucose metabolism in six out of nine patients. Five of the six patients who underwent early surgical treatment showed this kind of perfusion/metabolism discrepancy. Importantly, even the non-affected hemisphere in early infantile cases already lacked the normal hypoperfusion and hypometabolism patterns of immature frontal lobes, which was most prominent in case with poor surgical prognosis. In all six surgical patients, epileptic seizures appeared before 4 months of age. By contrast, none of the non-surgical patients had seizures before 4 months of age. In conclusion, although the number of patients examined is small and the result is still preliminary, the perfusion/metabolism discrepancy found in this study may show potential characteristic aspect of HME and further study with simultaneous EEG recording will make clear if this finding can be useful indicator for early surgical treatment in HME.
Postnatal evolution of cortical malformation in the "non-affected" hemisphere of hemimegalencephaly
2010, Brain and Development
A boy with epilepsy of neonatal onset was diagnosed with hemimegalencephaly (HME) based on the finding of an enlarged left cerebral hemisphere with dysplastic cortex over the frontal, parietal, and temporal lobes. Magnetic resonance imaging (MRI) showed an essentially unremarkable gyration pattern in the contralateral hemisphere. Ictal electroencephalography and magnetoencephalography revealed epileptic foci in the left hemisphere. Hyperperfusion and hypermetabolism were noted in comparison to the contralateral hemisphere, and these findings were consistent with the diagnosis of HME. Soon after hemispherotomy was performed at age 3 months, an epileptic focus appeared in the right hemisphere. The epilepsy remained intractable. Unexpectedly, dysplastic changes emerged over the right frontoparietal cortex at age 7 months as shown by MRI, and the cortical volume in this area was observed to be markedly increased at age 1 year and 8 months. This increase was associated with a distorted gray–white matter boundary. These findings contribute to our understanding of the pathogenesis of HME and may be helpful in determining the management approach for epilepsy in this entity.

View all citing articles on Scopus

View full text

Case reportBilateral neuropathologic changes in a child with hemimegalencephaly

Abstract

Prog Brain Res

Brain Dev

Dev Brain Res

Brain Res Rev

Dev Brain Res

Neuron

Unilateral megalencephaly: Correlation of MR imaging and pathologic characteristics

AJNR

MR of neuronal migration anomalies

AJNR

Hemimegalencephaly: A clinicopathological study of four cases

Neuropathol Appl Neurobiol

Hemimegalencephaly: Diagnosis and treatment

Dev Med Child Neurol

The role of hemispherectomy in the treatment of holohemispheric hemimegalencephaly

J Neurosurg

Operative strategies for patients with cortical dysplastic lesions and intractable epilepsy

Epilepsia

Surgically remedial diffuse hemispheric syndromes

Cerebral cortical dysplasia associated with pediatric epilepsy. Review of neuropathologic features and proposal for a grading system

J Neuropathol Exp Neurol

Neuropathologic findings in cortical resections (including hemispherectomies) performed for the treatment of intractable childhood epilepsy

Acta Neuropathol

Epidermal nevus syndrome: A neurologic variant with hemimegalencephaly, gyral malformation, mental retardation, seizures, and facial hemihypertrophy

Neurology

Hemimegalencephaly and neurofibromatosis

Neuropediatrics

Hypomelanosis of Ito and hemimegalencephaly

Clin Nerv Syst

The neuropathology of human symptomatic epilepsy

Neuropathologic findings in surgically treated hemimegalencephaly: Immunohistochemical, morphometric, and ultrastructural study

Acta Neuropathol

Case report
Bilateral neuropathologic changes in a child with hemimegalencephaly