Discrepancy Between Cerebral Structure and Cognitive Functioning: A Review.

Neuroscientists typically assume that human mental functions are generated by the brain and that its structural elements, including the different cell layers and tissues that form the neocortex, play specific roles in this complex process. Different functional units are thought to complement one another to create an integrated self-awareness or episodic memory. Still, findings that pertain to brain dysplasia and brain lesions indicate that in some individuals there is a considerable discrepancy between the cerebral structures and cognitive functioning. This seems to question the seemingly well-defined role of these brain structures. This article provides a review of such remarkable cases. It contains overviews of noteworthy aspects of hydrocephalus, hemihydranencephaly, hemispherectomy, and certain abilities of "savants." We add considerations on memory processing, comment on the assumed role of neural plasticity in these contexts, and highlight the importance of taking such anomalies into account when formulating encompassing models of brain functioning.

Bilateral population receptive fields in congenital hemihydranencephaly.

PURPOSE: Congenital hemihydranencephaly (HH) is a very rare disorder characterised by prenatal near-complete unilateral loss of the cerebral cortex. We investigated a patient affected by congenital right HH whose visual field extended significantly into the both visual hemifields, suggesting a reorganisation of the remaining left visual hemisphere. We examined the early visual cortex reorganisation using functional MRI (7T) and population receptive field (pRF) modelling. METHODS: Data were acquired by means of a 7T MRI while the patient affected by HH viewed conventional population receptive field mapping stimuli. Two possible pRF reorganisation schemes were evaluated: where every cortical location processed information from either (i) a single region of the visual field or (ii) from two bilateral regions of the visual field. RESULTS: In the patient affected by HH, bilateral pRFs in single cortical locations of the remaining hemisphere were found. In addition, using this specific pRF reorganisation scheme, the biologically known relationship between pRF size and eccentricity was found. CONCLUSIONS: Bilateral pRFs were found in the remaining left hemisphere of the patient affected by HH, indicating reorganisation of intra-cortical wiring of the early visual cortex and confirming brain plasticity and reorganisation after an early cerebral damage in humans.

Associative learning in premature hydranencephalic and normal twins.

A hydranencephalic infant lacking cerebral hemispheres and a normal twin were tested for associative learning. After repeated trials in which two stimuli were temporally paired, test trials were given in which the second stimulus was omitted. Cardiac orienting responses to stimulus omission indicated that learning had taken place in both infants.

An Amish founder variant consolidates disruption of CEP55 as a cause of hydranencephaly and renal dysplasia.

The centrosomal protein 55 kDa (CEP55 (OMIM 610000)) plays a fundamental role in cell cycle regulation and cytokinesis. However, the precise role of CEP55 in human embryonic growth and development is yet to be fully defined. Here we identified a novel homozygous founder frameshift variant in CEP55, present at low frequency in the Amish community, in two siblings presenting with a lethal foetal disorder. The features of the condition are reminiscent of a Meckel-like syndrome comprising of Potter sequence, hydranencephaly, and cystic dysplastic kidneys. These findings, considered alongside two recent studies of single families reporting loss of function candidate variants in CEP55, confirm disruption of CEP55 function as a cause of this clinical spectrum and enable us to delineate the cardinal clinical features of this disorder, providing important new insights into early human development.

Proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome or Fowler syndrome: Report of a family and insight into the disease's mechanism.

BACKGROUND: Fowler syndrome is a rare autosomal recessive disorder characterized by hydranencephaly-hydrocephaly and multiple pterygium due to fetal akinesia. To date, around 45 cases from 27 families have been reported, and the pathogenic bi-allelic mutations in FLVCR2 gene described in 15 families. The pathogenesis of this condition has not been fully elucidated so far. METHODS: We report on an additional family with two affected fetuses carrying a novel homozygous mutation in FLVCR2 gene, and describe the impact of known mutants on the protein structural and functional impairment. RESULTS: The present report confirms the genetic homogeneity of Fowler syndrome and describes a new FLVCR2 mutation affecting the protein function. The structural analysis of the present and previously published FLVCR2 mutations supports the hypothesis of a reduced heme import as the underlying disease's mechanism due to the stabilization of the occluded conformation or a protein misfolding. CONCLUSION: Our data suggest the hypothesis of heme deficiency as the major pathogenic mechanism of Fowler syndrome.

Residual visual function after loss of both cerebral hemispheres in infancy.

PURPOSE: To investigate whether and what kind of visual function is still present in the absence of both cerebral hemispheres. METHODS: Binocular visual function of five children who had suffered the loss of both cerebral hemispheres and the visual fields of 30 controls 5 to 12 months of age were examined according to a perimetric method based on forced-choice, preferential-looking methods. RESULTS: Results show that after the destruction of both cerebral hemispheres, a stimulus presented binocularly beyond 5 degrees eccentricity did not elicit a response. However, two children were still able to fixate steadily and to follow a stimulus presented binocularly within the central 5 degrees , with eye and head movements despite the absence of both cerebral hemispheres. One child responded only to a moving face or a moving drum with black and white stripes presented binocularly within the central 5 degrees but not to a moving spot of light. The binocular visual field of 30 controls 5 to 12 months of age almost reached the dimensions of the adult binocular visual field. CONCLUSIONS: Neural structures in the midbrain, including the superior colliculi and the pretectum, seem to be able to mediate visual function in the foveal and macular regions. These structures are, however, unable to mediate the presence of a functional visual field beyond 5 degrees eccentricity.

Brainstem mediation of the stapedius muscle reflex in hydranencephaly.

Hydranencephaly is a rare condition in which the cerebral hemispheres are absent at birth and are replaced by membranous sacs in a cerebrospinal fluid-filled cranium. Surviving hydranencephalic patients have a functional brainstem and possible remnants of the cerebral cortex. This case report examines hearing function and the integrity of the brainstem mediated stapedius muscle reflex (SMR) in an adult with hydranencephaly, using middle ear impedance change measures. The brainstem mediated ipsilateral and cross-brainstem contralateral SMRs were elicited in the right ear at normal threshold levels for noise bands of 0.25-1.0, 1.0-4.0, and 0.25-4.0 kHz (broadband), and at the sinusoidal frequencies of 0.5, 1.0, and 2.0 kHz. The ipsilateral and contralateral SMR decay rates were normal. The growth in the SMR amplitude in response to noise and pure tone stimuli from threshold to saturation over a 15-20 dB range was normal and showed essentially sigmoidal curves. The normal ipsilateral and crossed brainstem contralateral electrophysiological SMR in this hydranencephalic patient demonstrated the preservation of peripheral hearing reception and functional brainstem auditory afferent and efferent tracts and nuclei in the absence of corticofugal influence.

Electroencephalography, Doppler vascular scanning, and single photon emission computed tomography in a child with hydranencephaly and intractable seizures.

In a child with hydranencephaly and refractory seizures, the electroencephalogram showed a flat isoelectric pattern with no significant slow waves or epileptiform activity; cranial computed tomography, magnetic resonance imaging, Doppler vascular scanning, and single photon emission computed tomography (SPECT) were done to define the pathogenesis of the seizures. The investigations were suggestive of a lack of significant cortical, subcortical, or thalamic structures with hypoplasia of the vermis and cerebellum. SPECT showed little activity in the base of the brain and cerebellum. The cause of the seizures remained unclear in spite of the investigations.

Electrophysiological responses in hydranencephaly.

We recorded electrophysiological responses, both electroretinograms (ERGs) and visual evoked responses (VER), at 4 and 21 months of age in a child with hydranencephaly. As expected, the ERG was normal. Despite the apparent absence of most of the cerebral cortex, a VER was present at both visits. The child's visual performance definitely improved both subjectively and electrophysiologically. The VER contained multiple early components in contrast to previous reports, where only a slow, monophasic response was detected.

Polygraphic characterization of the sleep-epilepsy patterns in a hydranencephalic child with severe generalized seizures of the Lennox-Gastaut syndrome.

This is the report of a hydranencephalic child with severe generalized seizures of the Lennox-Gastaut Syndrome (LGS) who lacked the development of the entire cerebral hemispheres and had preserved the brain stem, cerebellum, hypothalamus and a portion of the thalamus as evidenced by radiological and/or physiological studies. Conventional polygraphic sleep studies in these patients showed presence of scalp EEG and other peripheral, somatic and vegetative signs characterizing the wakefulness, quiet sleep and active sleep stages. Absence of the vertex waves and disrupted sleep spindles were the major qualitative EEG abnormalities. In contrast, quantitative abnormalities in duration, latency and number of sleep cycles found in this patient were similar to those found in other children with Idiopathic Lennox-Gastaut Syndrome (ILGS). A substantial reduction in the number of interictal EEG spikes and a shortening of the ictal clonic EEG activities without concomitant EMG jerks were the most distinct epileptiform abnormalities in this child. In contrast, his basic polygraphic patterns of the tonic and apneic seizures were similar to those found in other children with ILGS. Data obtained from this child suggest that both the sleep stages and the generalized seizures of the ILGS basically depend more on the integrity of the brain stem than on the telencephalic structures.

Hydranencephaly and maximal hydrocephalus: usefulness of electrophysiological studies for their differentiation.

The EEG was evaluated in three cases of hydranencephaly and two cases of maximal hydrocephalus, and the visual evoked potential was studied in one case each of hydranencephaly and maximal hydrocephalus. The EEG tracing of hydranencephaly typically showed a flat pattern in most bipolar derivations because of the differential amplification of the same activity from remote generators. However, the EEG of maximal hydrocephalus did not demonstrate a flat pattern in bipolar as well as referential derivation, and the activities were different from various electrodes in referential derivation. The visual evoked potential of maximal hydrocephalus showed a normal pattern, while that of hydranencephaly showed no response. Electrophysiological examinations (such as EEG and visual evoked potential) are useful for differentiation of hydranencephaly and maximal hydrocephalus in cases whose computed tomographic scans do not provide clear differentiation.

Circadian rhythm in patients with hydranencephaly.

Circadian rhythm and sleep were studied in three hydranencephalic infants who were diagnosed on the basis of computed tomographic and/or magnetic resonance imaging scans and electrophysiologic findings. In all three cases, although the active sleep cycle was preserved, quiet sleep decreased and indeterminate sleep increased. The sleep-circadian rhythm was disturbed in all three cases. The hormone secretion rhythm was studied in two cases (cases 1 and 3). In both cases, cortisol secretion showed two or three peaks during the day. In one case (case 3), growth hormone secretion did not show sleep enhancement. Prolactin secretion showed an increase during sleep in both cases. The circadian rhythm of body temperature appeared at 6 months of age and disappeared after 1 year of age in case 1. Case 2 did not show a circadian rhythm of body temperature, but case 3 did at 2 years 6 months of age. However, it was thought that the circadian rhythm of body temperature in case 3 was a false one due to severe opisthotonus. Thus, it is suggested that the development of the circadian rhythm may require the rostral brain structure more than the midbrain and that there may be multiple oscillators in humans.

Hemihydranencephaly: case report and literature review.

Hydranencephaly is a severe brain condition characterized by complete or almost complete absence of cerebral cortex with preservation of meninges, basal ganglia, pons, medulla, cerebellum, and falx. It has been ascribed to different causes (infections, irradiations, fetal anoxia, medications, twin-twin transfusion), all leading to vascular disruption. Hemihydranencephaly is an extremely rare condition in which the vascular anomaly is unilateral. We report on a patient who was suspected to have hydrocephalus in utero; a brain magnetic resonance imaging scan showed left-sided hydranencephaly with preservation of basal ganglia. The patient developed signs of right hemiparesis but notably has only mild language delay. The available literature on hemihydranencephaly is reviewed.

Body movements during sleep in full-term newborn infants.

Body movements during sleep were observed in 14 full-term sick newborn infants such as perinatal asphyxia, purulent meningitis, meconium aspiration syndrome, melena, porencephaly, and hydranencephaly. Five newborn infants who had recovered from transient vomiting were examined as control. Infants with minimally depressed background EEG showed an increase of generalized movement (GM) and localized tonic movement (LTM) in quiet sleep. Hydranencephalic infants revealed an increase of generalized phasic movement (GPM) in active and quiet sleep. On the other hand, a decrease or an absence of body movements was observed in infants with severe EEG abnormalities such as moderate, marked and maximal depression. Hydranencephalic and porencephalic neonates showed a decrease of LTM in active sleep. One infant with purulent meningitis, showing markedly depressed EEG, revealed GPM-like movements of much longer duration. The follow-up study revealed that the absence of body movements or the increase of GPM might indicate a very poor outcome, whereas the presence of LTM, even in a small amount, suggested the preservation of cortical functions. The increase of body movements was also considered to correlate with sleep disturbance and served to indicate a brain dysfunction.

Electrophysiological study on hydranencephaly.

An electrophysiological study was performed on 2 children with hydranencephaly diagnosed by CT and/or MRI. Case 1 was a 4-month-old boy who had no rostral tissues above the midbrain. Case 2 was a 5-year-old boy in whom CT showed retention of the thalamus. Short latency somatosensory evoked potentials (SSEP) in both cases exhibited the absence of cortical activity (N1 and P4) with the preservation of waves of brain stem origin. However, in case 1, wave component No was not observed, while No was seen in case 2. It was postulated, thus, that the No component of SSEP on median nerve stimulation in children, which corresponds to N16 in adults, may originate in the thalamus.

Severe outcome of brain perfusion failure: a pre-hydranencephalic state?

Four children surviving severe hypoxic-ischemic brain damage showed subtotal destruction of the cerebral hemispheres, with partial preservation of some infratentorial and supratentorial brain structures. True multicystic encephalopathy features were identified in two cases on CT scanning. The other patients showed more pronounced brain tissue destruction, with overall malacia of the hemispheres. An echographic study demonstrated that the brain damage occurred progressively, within about one month, and was preceded by oedema, white matter malacia and cavitation. The role of the compensatory mechanisms responsible for preservation of structures supplied by the vertebral-basilar circle is discussed. The authors suggest that the observed outcome could be considered a stage immediately preceding the most severe damage represented by hydranencephaly.

Hydranencephaly: sleep and movement characteristics.

Sleep and body movements were studied in 2 hydranencephalic neonates using visual analysis and polygraphic recording. They manifested periodic alternation of active and quiet sleep with peculiar movements of bilateral synchronized patterns. Generalized phasic movements were significantly increased and localized tonic movements were reduced. In view of the complete absence of cerebral hemisphere in this disorder, the movement of bilaterally synchronized pattern or increase of generalized phasic movement are considered to be generated from the basal ganglia and/or brain stem without cerebral hemisphere, whereas, localized tonic movements have more cortical correlation in its organization. The observation of body movements may be useful in detecting hydranencephaly in early infancy.

Nocturnal sleep in infants with congenital cerebral malformation.

Sleep EEG patterns in 17 infants with cerebral malformations (4 months to 4 years of age) were studied throughout nocturnal sleep and the following results were obtained. Seven cases evidenced normal sleep/wakefulness EEG patterns that could be classified into 6 stages. Ten cases showed abnormal sleep EEG patterns as follows: absence of sleep spindles (n = 7) which included cases of absence of EEG patterns characteristic of wakefulness, NREM sleep and REM sleep (n = 5), no characteristic EEG patterns of stages 1-4 (n = 1) and stages W, 1, 2 and REM (n = 1) and the remaining cases with absence of spindles (n = 1), and spindles with an extremely low incidence (n = 2). Short sleep and long awaking times, and no delta rhythmicity during the night, were noted in 5 out of 17 subjects. A significant decrease of DQ was found in subjects with indistinguishable stages including stages W, 1, 2 and REM, as compared with those patients whose stages were all distinguishable.

Sinusoidal fetal heart rate pattern in hydranencephaly. A case report.

A sinusoidal fetal heart rate pattern developed immediately after a meperidine/promethazine injection in a fetus with hydranencephaly. Various etiologies of sinusoidal fetal heart rate pattern, as well as possible mechanisms leading to this entity, have been proposed.

Brain functions of an infant with hydranencephaly revealed by auditory evoked potentials.

Hydranencephaly is a severe condition of brain characterized by the almost complete absence of the cerebral hemispheres with the thalamus, cerebellum and brainstem being preserved. This paper reports hydranencephaly in a 3-month-old boy. Cranial magnetic resonance imaging (MRI) revealed the condition and an auditory evoked potential study which was performed in order to investigate residual brain function. They showed normal auditory brainstem function but no appearance of other auditory evoked potentials originating from the higher brain.