Treatment with a protein restricted diet (1 g/ kg/day), sodium benzoate (200 mg/kg/day) and arginine (3 mmol/kg/day) led to reduction of the serum ammonia level and a return of conciousness of the patient. The serum am­monia level has been maintained between 100 J,lg/dl and 150 J,lg/dl thereafter.

Discussion

We have observed other cases of genetic hyper­ammonemia (2 cases of carbamyl phosphate synthetase I (CPS I) deficiency [4], 2 cases of citrullinemia and 2 cases of methylmalonic acidemia). Their CT scans were normal except for one case of CPS I deficiency who had pro­longed hyperammonemia, and had findings similar to the present case of OTC deficiency. Since the other cases were treated immediately after the onset, it is suggested that the CT scan abnormalities were related to the degree of hyperammonemia and the duration of the illness. The exact cause of this low density is unknown. In our case, the lack of vascular change on angiography mitigates against a stroke. Cerebral edema is a well-known com­plication of metabolic encephalopathy in diabe­tic ketoacidosis [5], maple syrup urine disease [6] and Reye syndrome [7-9], all of which may have abnormal brain CT scans. CT demon­strates the cytotoxic cerebral edema found pathologically in th~ acute stage of hyper­ammonemia [10]. In Reye syndrome, edema

• of the white matter is largely due to myelin bleb formation and is largely responsible for its low density on CT [9]. Lipid deposition within vascular pericytes in the white matter may contribute to this low density [9] . Similar pathological changes no doubt occur in acute hyperammonemia due to urea-cycle enzy­mopathies and other causes.

We suggest that a CT scan of the brain may be helpful in patients with acute hyperam­monemia, and that serum ammonia levels be measured in children with an acute encepha­lopathy even if the CT scan demonstrates a focal lesion.

References 1. Russell A, Levin B, Oberholzer VG, Sinclair L.

Hyperammonemia: A new instance of an inborn enzymatic defect of the biosynthesis of urea. Lancet 1962;2:699-700.

2. Hopkins IJ, Connelly JF, Dawson AG, Hird FIR, Maddison TG. Hyperammonaemia due to ornithine transcarbamylase deficiency. Arch Dis Child 1969;44:143-8.

3. Kendall BE, Kingsley DP, Leonard JV, Lingam S, Oberholzer VG. Neurological features and computed tomography of the brain in children with ornithine carbamyl transferase deficiency. J Neurol Neurosurg Psychiatry 1983;46:28-34.

4. Kakinuma H, Ohtake A, Ogura N, et al. Two sib­lings with complete carbamyl phosphate synthe­tase I deficiency. Acta· Pediatr Jpn Overseas Edition 1984 (in press).

5. Duck SC, Weldon VV, Pagliara AS, Haymond MW. Cerebral edema complicating therapy for diabetic ketoacidosis. Diabetes 1976;25:111-5.

6. Lungarotti MS, Calabro A, Singnorini E, Garibaldi LR. Cerebral edema in maple syrup urine disease. Am J Dis Child 1982;136:648.

7. Giannotta SL, Hopkins I, Kindt GW. Computer­ized tomography in Reye syndrome: Evidence for pathological cerebral vasodilation. Neuro­surgery 1978;2:201-4.

8. Coin CG, Pennink M, Gray R, Stowe F. Cerebral computed tomography in Reye syndrome. J Corhput Assist Tomogr 1979;3:276-7.

9. Russel EJ, Zimmerman RD, Leeds NE, French J. Reye syndrome: Computed tomographic documentation of disordered intracerebral struc­ture. J Comput Assist Tomogr 1979;3:217-20.

10. Shih V. Urea cycle disorders and other congenital hyperammonemic syndromes. In Stanbury JB, Wyngaarden JB, Fredrickson DS, eds: The meta­bolic basis of inherited disease. 4th Ed. New York: McGraw-Hill Book Co, 1978:362-86.

An Autopsy Case of Hemimegalencephaly

Maria Dambska, MD, Krystyna Wisniewski, MD and Joanna H Sher, MD

This case report is a neuropathological study of a ten-month-old infant with unilateral megalence­phaly. In this anomaly neuronal migration defect and disturbances of cortical organization result­ing in micropolygyria were the most striking neuropathological feature.

Dambska M, Wisniewski K, Sher iH. An autopsy case of hemimegalencephaly. Brain Dev 1984;6:60-4

Megalencephaly with unilateral congenitally determined anomalies, the so-called "true" hemimegalencephaly, is a rare condition, even within the group of megalencephalic brains [1-3]. Since its relationship to other brain malformations is still a matter of debate we would like to discuss the neuropathological findings in one hemimegalencephalic case, despite the lack of available clinical data.

Case Presentation

This female infant with developmental delay was suffering from frequent seizures since her early days of life, and died suddenly at the age of ten months. No other clinical data were known.

The general autopsy did not reveal the cause of death. Pathological changes were restricted to the central nervous system. The cerebral hemispheres were very large. Brain weight was of 1,350 g (the norm for this age is ±800 g), and that of the cerebral hemispheres was 1,200 g. The left hemisphere was larger than the right, with external pachygyric convolu­tions (Fig 1). The right hemisphere looked normal.

On microscopic examination small foci of micropolygyria in the neocortex were the only abnormality in the right hemisphere. The myelination of the white matter was nor­mal for a ten-month-old infant.

From the Medical Research Center, Polish Academy of Science, Warsaw (MD); New York State Office of Mental Retardation and Developmental Disabilities; Institute for Basic Research in Developmental Dis­abilities, Staten Island, New York (KW); Downstate Medical Center, Brooklyn, New York (JRS).

Received for publication: November 24, 1983. Accepted for pUblication: March 1, 1984.

Key words: Congenital malformations, hemimegal­encephaly, phakomatosis, micropolygyria, neuronal migration defect.

Correspondence address: Dr. K Wisniewski, Institute for Basic Research in Developmental Disabilities, 1050 Forest Rill Road, Staten Island, New York 10314, USA.

The left hemisphere showed an unusually thick cortical ribbon with a majority of micro­gyric patterns. The external sulci did not correspond to the microconvolutions of the ex­ternal cortical layers. The abundant leptomenin­geal glioneuronal heterotopias, particularly localized in some shallow sulci, contributed to the smooth appearance of the external surface of this hemisphere. The whole structure of the neocortex was disturbed by no distinct borderlines between the internal cortical layers which remained parallel to the cortical surface under microconvolutions of the external layers.

Unusually large pyramidal neurons were disseminated in all cortical levels including the leptomeningeal heterotopias. They were partly present in small clusters. The large neurons were of bizzare shape and had very large nuclei. Some of them had defectively oriented apical dendrite (Fig 2a). Sporadic fibrillary tangles were seen in these cells (Fig 2b). Many hypertrophied astrocytes (Fig 3) were found in the cortex around the vessels. These were also disseminated and clustered in the external submeningeallayers.

The neuronal population in neocortex did not present important degenerative lesions. Damaged neurons were observed more often at the cortico-subcortical borderline. There, scattered calcifications were also found.

No myelin sheaths were visible either sub­cortically or in the central part of the centrum semiovale. Myelin was seen within the corpus callosum and internal capsule, but these struc­tures were paler than the parallel ones in the opposite hemisphere. Subtotal necrotic changes and secondary fibrillary gliosis were found in the subcortical area. There, fragmented nerve fibers and features of axonal degeneration were frequent. Perivascular and disseminated calcifications were abundant (Fig 4). Focal neuronal heterotopias were subcortically dis­persed, and often degenerated and calcified.

The phylogenetic ally older hippocampal cortex did not present structural anomalies. The basal ganglia looked normal, only showing disseminated calcium deposits in the striatum and some myelin degeneration in the internal capsule. No abnormalities were found in the cerebellum and in the brain stem except for the left pyramidal tract which was smaller and had paler myelin than the right one.

Dambska et al: An autopsy case of hemimegalencephaly 61

Fig la Hemimegalencephaly. The left hemisphere is larger than the right with wide convolutions and micropolygyria; b: Polymicrogyric pattern of the cortex. Cresyl violet. Magn. 66 x .

62 Brain & Development, Vol 6, No 1, 1984

Fig 2A Giant neurons in the cortex of left hemi­sphere. Cresyl violet. Magn.

S'.] 60 x; B: Fibrillary tangles

in the giant neurons. Bodian-PAS. Magn. 664 K .

,. - ... ... ,. •

·'k . , •

•

, .. ' •

•

Fig 3 Giant astrocytes in " the cortex of left hemi­

sphere. Cajal. Magn. 160 x.

I • • •

• ~

\

~. • , 0

• •

• • • • •

• , • • • •

Discussion

Frequent seizures and developmental delay were the only clinical events known in the above presented case of unilateral megalen­cephaly . They have been observed in the majority of reported cases. The anomalies of neuronal migration and disturbances of cortical organization resulting in micropolygyria were the most striking morphological features in the hypertrophied hemisphere. Many giant neurons disseminated or clustering in the cortex

... •

• • •

•

,

•

Fig 4 Perivascular calcifi-• cations in the white

matter. H.E. Magn. 416 x .

were similar to those observed by Bignami et al [4] , Tjiam et al [5] and Manz et al [6] . Cyto­photometric, quantitative histochemical and biochemical studies performed by these authors revealed the increase of nuclear and nucleolar volume. Manz et al [6] suggested heteroploidy of chromosomlll DNA. The picture of giant neurons evoked some similarities to tuberous sclerosis mentioned by Tjiam et al.[5] . How­ever, although astrocytes increased in number in the above cited cases, they showed only moderate hypertrophy and did not resemble

Dambska et af: An autopsy case of hemimegafencephafy 63

those in Bourneville disease. On the other hand, Townsend et al [7] discussed three cases of hemimegalencephaly and found in one of them not only hypertrophied neurons, but also large astrocytes suggesting evolution to­wards neoplasm. Giant astrocytes disseminated in the cortex and in the subcortical area were present in our case. The subcortical partial and focal total necrosis was unusual. Since these lesions with disseminated calcifications were subjacent to the micropolygyric cortex, they seemed secondary to cortical abnormali­ties. The reactive astrocytes in damaged white matter compared with more hypertrophied and bizarre ones in the cortex with no evident necrotic lesions inclines us to believe that these cortical astrocytes are primarily "giant."

These observations seem consistent with primary overproduction and overgrowth of neuroectodermal cells in our case of "true" hemimegalencephaly. These morphological ob­servations support the hypothesis [7] that such cases constitute a separate type belonging to the large group of phakomatoses.

64 Brain & Development, Vol 6, No 1, 1984

References 1. Dekaban AS, Sakuragawa N. Megalencephaly.

In: Vinken PJ, Bruyn GW, eds. Handbook of clinical neurology vol 30. Congenital malfor­mations of the brain and skull. Part 1. Am­sterdam: North Holland, 1977: 647-60.

2. Norman RM. Megalencephaly. In: Blackwood W, Corsellis J, eds. Greenfield's neuropathology. London: Arnold, 1963:350.

3. Hallervorden J. Angeborene Hemihypertrophie der linken Korperhiilfte einschliesslich des Gehirns. Zentralbl Neurol Psychiatr 1923;33: 518-9.

4. Bignami A, Palladini G, Zappella M. Unilateral megalencephaly with nerve cell hypertrophy. Brain Res 1968;9: 103-14.

5. Tjiam AT, Stefanko S, Schenk VWD, de Vlieger M. Infantile spasms associated with hemihypsar­rhythmia and hemimegalencephaly. Dev Med Child NeuroI1978;20:779-98.

6. Manz HJ, Phillips TM, Rowden G, McCullough DC. Unilateral megalencephaly, cerebral cortical dysplasia, neuronal hypertrophy and heterotopia: Cytomorphometric, fluorometric cytochemical and biochemical analyses. Acta Neuropathol (Berl) 1979;45:97-103.

7. Townsend JJ, Nielsen SL, Malamud N. Unilateral megalencephaly: Hamartoma or neoplasm? Neu­rology 1975;25:448-53.