Usefulness of multidetector-row computerized tomographic angiography for the surgical planning in stereoelectroencephalography.

PURPOSE: Surgical planning of depth electrode implantation in stereo-electro-encephalography (SEEG) routinely uses magnetic resonance imaging (MRI) alone. Accurate visualization of arteries and veins in the vicinity of the electrode is essential to plan a safe trajectory to presumably reduce the risk of intracranial bleeding. The goal of this study was to compare multidetector row computerized tomographic angiography (MDCTA) with MRI for the visualization of vessels along each planned trajectory in patients who undergo SEEG. MATERIALS AND METHODS: Ten consecutive patients who were scheduled to undergo SEEG procedure were included. T1-weighted gadolinium-chelate enhanced MR sequence, stereotactic MDCT and MDCTA were performed after fixation of Leksell's frame. For each of the 106 planned stereotactic trajectories, the number of vessels in a 4.0mm diameter circle around the trajectory from the dura mater to the target that were visible on MDCTA were compared to that of visible vessels in the same areas on MRI. RESULTS: Ten vessels (10/106; 9.4%) were seen on MRI and 66 (66/106; 62.3%) on MDCTA (P<0.0001). All vessels visible on MRI were visible on MDCTA. The difference in number of visible vessels between the two techniques remained significant for the different lobes (i.e., frontal lobe, temporal lobe and parieto-occipital lobe). CONCLUSION: MDCTA enabled visualization of more vessels than MRI based SEEG. MDCTA may help neurosurgeons better define the trajectory of the electrode and reduce the risk of intracranial bleeding.

Impact of deep brain stimulation on pharyngo-esophageal motility: a randomized cross-over study.

BACKGROUND: Bilateral subthalamic nucleus (STN) stimulation is used to alleviate Parkinson's disease (PD) motor symptoms. Recently, it has been shown that this therapeutic also increased gut cholinergic contractions. We therefore investigated the effect of STN stimulation on esophageal motility in an interventional randomized study. METHODS: Sixteen humans PD patients (4 women, 12 men; age: 62.4 ± 9.3-years old) who underwent STN stimulation for at least 6 months were randomly evaluated with either stimulator turned OFF then ON, or inversely. Esophageal high resolution manometry was performed at the end of each ON and OFF period, with a 5 min resting period followed by ten swallows of 5 mL. KEY RESULTS: During the ON, an increase in the distal contractility index was found (OFF: 1750 ± 629 vs ON: 2171 ± 755 mmHg/cm/s; p = 0.03), with no difference in the distal front velocity. A decrease in the integrative relaxation pressure of the lower esophageal sphincter (LES) was noted (OFF: 11.1 ± 1.8 mmHg vs ON: 7.2 ± 1.8 mmHg; p < 0.05) in ON. The LES resting pressure remained unchanged during the two periods. This resulted in a decrease in the intrabolus pressure (p = 0.03). No difference was observed for the upper esophageal sphincter, nor the pharyngeal contraction amplitude and velocity. CONCLUSIONS & INFERENCES: In conclusion, STN stimulation in PD patients increased esophageal body contractions and enhanced the LES opening. This suggests that the nigrostriatal-striatonigral loop is involved in the control of esophageal motility.

Brain metastasis from renal cell carcinoma.

BACKGROUND: Patients with brain metastasis (BM) from renal cell carcinoma (RCC) have a poorly known prognosis due to the rarity of this disease. The aim of our study was to assess the outcome of patients with a BM due to RCC, and to determine the predictive factors for survival. METHODS: Consecutive patients who underwent treatment between 1997 and 2012 were identified retrospectively from a database (n=28, median age of 57.8 years, sex ratio M/F: 3.7). Main criteria collected concerned survival time. Other data collected were relative to initial histology, clinical findings at the time of BM diagnosis (diagnosis circumstances, KPS), radiological findings and BM characteristics (number, size and localization), treatment of BM (including surgery, stereotactic radiosurgery [SRS], systemic treatments, whole brain radiotherapy [WBRT]) and the outcome of surgery if performed. Statistical analysis of survival was performed using the Kaplan-Meier method. RESULTS: Median survival was 13.3 months, 1-year survival was 60.2%, 2-year survival was 16.4%. Univariate analysis showed the existence of intracranial hypertension (P=0.01), other systemic metastasis (P=0.049), the absence of deep metastasis (P=0.03) which are all linked to shorter survival. Age, KPS, initial histology of RCC, number, size, localization, and hemorrhage in BM were not correlated to survival. The median survival in the surgical resection group was 25.3 months versus 8.6 months (P=0.02). The main criteria for the selection of the surgical group were a single BM (P=0.04), and superficial metastasis (P=0.02). CONCLUSIONS: Three predictive factors for longer survival in BMRCC were the absence of intracranial hypertension, the absence of acute metastasis and the absence of extracranial metastasis. Surgical removal, when possible, seems to benefit patient survival.

Endoscopic 3rd ventriculocisternostomy: procedural complications and long-term dysfunctions?

BACKGROUND AND PURPOSE: The endoscopic third ventriculostomy (ETV) has become the treatment of choice for managing non-communicating hydrocephalus. The aim of this study was to evaluate the efficacy and the morbi-mortality of this procedure and its long-term outcome. PATIENTS AND METHODS: This retrospective study involved 82 consecutive patients treated for non-communicating hydrocephalus by ETV, in a single centre, between June 1999 and November 2008. The main criterion of efficacy was clinical improvement with shunt independence. The secondary criteria were the ventricular size (third and lateral ventricles) outcome and the procedural morbidity and mortality. In order to determine the predictive factors of dysfunction, a uni- and multivariate analysis was conducted. RESULTS: Divided in two groups, the overall success rate was 65.4% in the paediatric group (n=26) and 83.9% in the adult group (n=56), after respectively a mean follow-up of 59.1±36.7 and 49.3±27.7 months. A procedural complication occurred in 5 patients (6.1%), with no procedure-related death. The predictive factors of ETV failure were an infectious aetiology and an age less than 16. Changes in ventricular size and success rate were independent. CONCLUSIONS: ETV is an effective procedure at long-term for the management of non-communicating hydrocephalus with low morbidity. Therefore, it should be considered as first-line treatment. Cerebrospinal meningitis infection and young age both expose patients to possible dysfunction.

Distal middle cerebral artery aneurysm: A proposition of microsurgical management.

OBJECTIVES: Based on a cohort of patients treated on distal middle cerebral artery (MCA) aneurysm by microsurgical approach, the objectives were to assess the following: the postoperative functional outcome, study the causes of early neurological deterioration and to determine the predictive factors of favourable outcome. PATIENTS AND METHODS: From a neurovascular prospective database, this retrospective longitudinal study included all the patients treated for cerebral aneurysm located on the distal segment of the MCA over two decades (January 1990-December 2011). The patients were all treated by microsurgical clipping exclusion. Any aneurysm was associated to infectious angiopathy. Data were retrieved from the patient's medical charts. The outcome was analysed twice: during the immediate postoperative period and at 6 months according to the modified Rankin scale. The relative risk was estimated for each variable and the prognostic factors were assessed using a multivariate logistic regression model (P<0.05). RESULTS: Twenty-eight patients, mean age 40±13.3 years (median: 43 years; range 6-70 years) were divided into the ruptured group (n=20) and unruptured group (n=8). In the ruptured group, the initial clinical status was good (WFNS I-III) in 12 patients (60%) and poor in eight (40%) with an intracerebral haematoma (ICH) in 11 (55%). For both groups, the aneurysm location on the distal MCA decreased at a rate from 64.8% of the insular segment to 25% of the opercular then 10.7% to the cortical. During the hospital stay, neurological deterioration occurred in 16 patients (57.2%). The diagnosed causes were cerebral ischaemia in 10 (35.6%), initial ICH in three (10.7%), hydrocephalus in two (7.1%) and epilepsy in one (7.1%). At 6 months, a favourable outcome (mRS 0-2) was observed in 19 patients (68.1%), a definitive morbidity in seven (24.9%) and death in two (7.2%). Based on the prognostic factors, only the absence of immediate postoperative neurological deterioration was identified as significant for a favourable outcome. CONCLUSION: These rare cerebral aneurysms resulted in a high proportion of poor initial status related to a frequent ICH. Cerebral ischaemia was a major cause of the immediate neurological deterioration and the absence of immediate neurological deterioration was the single identified prognostic factor.

Lumbar spinal stenosis: which predictive factors of favorable functional results after decompressive laminectomy?

BACKGROUND AND PURPOSE: Long-term results of decompressive laminectomy in degenerative lumbar stenosis have been studied in only six prospective studies. The objective of our study was to evaluate the functional outcome at long term of patients after decompressive laminectomy in lumbar stenosis and to determine predictive factors of favorable outcome. METHODS: A prospective cohort data were collected by an independent observer five years after decompressive laminectomy for degenerative lumbar stenosis. The endpoint was the assessment of the Beaujon score for functional evaluation. The result was considered as favorable if the Beaujon score increased by at last five points between the preoperative stage and at follow-up examination. Logistic regression was then performed with univariate and multivariate analysis to reveal predictive factors of good long-term outcome (P≤0.05). RESULTS: The preoperative characteristic of our population (n=98) was a mean age of 67.3±8.8 years, a low comorbidity (mean Charlson score=2.8±1.5), overweight status (BMI=29.4±6.3) and the mean Beaujon score was 9.3±3.1. At five years after surgery, the mean Beaujon score became 14.1±4.2. Favorable functional outcome concerned 45.9% of our series. The predictive factor of favorable outcome identified in the univariate analysis the neurological deficit (P=0.05) and in the multivariate analysis the low comorbidity (P=0.01). CONCLUSION: The long-term results of surgical treatment of lumbar spinal stenosis were moderate with an improved outcome in 49.5% of cases in our study. The only independent factor to a favorable outcome was the low comorbidity.

Study of the involvement of pancreastatin in the physiopathology of diabetes mellitus associated with nonsecreting pituitary adenomas.

Pancreastatin, derived from chromogranin A, inhibits insulin and stimulates glucagon secretion in rodents. Immunohistochemistry localised pancreastatin in human pancreatic islet cells and gonadotroph pituitary cells. Nonsecreting pituitary adenomas, frequently associated with diabetes mellitus, arise quasi-constantly from gonadotroph cells. We evaluated the possible involvement of pancreastatin in the physiopathology of diabetes mellitus associated with nonsecreting pituitary adenomas. Plasma pancreastatin levels were measured by radioimmunoassay in 5 groups of subjects: 10 patients with nonsecreting pituitary adenomas associated with diabetes mellitus (group I), 10 patients with nonsecreting pituitary adenomas without diabetes (Group II), 10 patients with ACTH or GH-secreting pituitary adenomas and diabetes mellitus (Group III), 10 diabetic patients without pituitary adenomas (Group IV), and 10 healthy controls (Group V). Kidney and liver functions were normal in all of them and no patient was treated with a proton pump inhibitor. All pituitary adenomas were trans-sphenoidally removed. Immunohistochemistry against pancreastatin was performed in 5 patients of each of the 3 groups of pituitary adenomas. Plasma pancreastatin levels were not different between the different groups: 182±46 pg/ml (Group I), 195±57 pg/ml (Group II), 239±42 pg/ml (Group III), 134±31 pg/ml, (Group IV), and 122±29 pg/ml (Group V). In contrast, they were significantly (p<0.05) higher before (391±65 pg/ml) than after trans-sphenoidal surgery (149±18 pg/ml) without post-surgical change in diabetes. An immunostaining against pancreastatin was found in a majority of pituitary adenomas, associated or not with diabetes mellitus. These results argue against a role of pancreastatin in the pathogenesis of diabetes mellitus associated with nonsecreting pituitary adenomas.

Elderly patients with aneurysmal subarachnoid hemorrhage: Coils but also clips.

The ageing of the population in good health or without severe morbidity expose them to the occurrence of a subarachnoid hemorrhage (SAH) and requires effective management. Currently, the pertinence of cerebral aneurysm treatment by clipping or coiling is accepted for patients in the 8th or 9th decade of life, and the risk of postoperative morbidity induced by our therapeutic alternative must be carefully assessed. In these decades, the female/male sex ratio for aneurysmal SAH was greater in female who had a 1.6 times higher ratio than in male. The initial clinical status did not appear worse with age despite the frequent severity of bleeding observed on CT scan probably due to the large subarachnoid space. The aneurysm distribution and size were similar to those classically reported in the global population. The endovascular (EV) coiling appears as the first option with a favorable outcome rate estimated at 48% to 63%. Nevertheless, the benefit of EV coiling compared to microsurgical clipping for treatment of ruptured aneurysm in the elderly has not been demonstrated in a large randomized study. This is the reason why the vascular section of the French Society of Neurosurgery developed a prospective and randomized study of the aneurysmal SAH (PHRC 2007-042/HP) on the elderly patients.

[Rebleeding from a vertebral artery dissection in a child: an inflammatory vasculopathy?]. / Resaignement d'une dissection d'artère vertébrale chez un enfant : une vasculopathie inflammatoire ?

We present a case of a rebleeding remote from a vertebral artery dissection associated with subarachnoid haemorrhage. A 7-year-old boy without any antecedent presented a traumatic dissection of the vertebral artery with subarachnoid haemorrhage. After a conservative treatment, the morphology of the vertebral artery became normal and the boy was asymptomatic. Four months later, a rebleeding occurred on the same vertebral artery, whose morphological review was normal. Mechanisms and cases of rebleeding in the literature are discussed. An inflammatory vasculopathy was suspected and discussed.

[Clinical and ossification outcome of custom-made hydroxyapatite prothese for large skull defect]. / Tolérance clinique et degré d'ossification des cranioplasties en hydroxyapatite de larges défects osseux.

OBJECTIVE: Cranioplasty is an everyday concern in neurosurgery, especially in decompressive craniectomy cases. Our surgical team uses custom-made hydroxyapatite implants for large and/or complex defects. PATIENTS AND METHOD: Eight patients had a custom-made prosthesis. Each of them has been reviewed by an independent observer. Each patient described his feeling of satisfaction, using a questionnaire, graduated from "A" (really satisfied) to "D" (unsatisfied). Each of them also underwent a CT-scan (helicoidal acquisition, 0.6mm thick for multiplanar reconstruction) to evaluate qualitatively the ossification graduated from "0" (no ossification) to "5" (continuous ossification). Maximal under-prosthetic bone thickness, intra-prosthetic calcic density were also reported. RESULTS: Supervision delay was 43.7 months [6-99 months], average defect surface was 85.5 cm(2) [27.6-137.6 cm(2)], the craniectomy etiologies were intracranial hypertension (seven patients) and calvarial invasion (one patient). Implant tolerance was reparted in "A" score (50%) and "B" score (50%). Concerning ossification, six patients (75%) had a score of "2" or less and two patients had a score of "3" or "4". DISCUSSION: Hydroxyapatite custom-made implants for cranioplasty appear to be ideal for good aesthetic and tolerance results, but their ossification is hardly analyzed due to the prosthesis density higher than the bone's density. This is why we recommend them for children and in cases of complex defects such as pterion location.

Effect of unilateral subthalamic deep brain stimulation on rat digestive motor activity.

UNLABELLED: A significant proportion of patients with Parkinson's disease suffers from digestive symptoms. Bilateral deep brain stimulation of the subthalamic nucleus has become a reliable therapeutic option for parkinsonian patients, but its effects on digestive motility remain poorly investigated. The aim of our study was to assess whether subthalamic stimulation could induce changes in gastric, colonic, and rectal motility and modulate brain centers involved in gut motility. METHODS: In anesthetized rats, unilateral subthalamic nucleus stereotactic implantation was performed while intra-gastric, -colonic, and -rectal pressures were recorded during the ON and OFF periods of the stimulation. c-Fos protein expression was quantified by immunostaining in the nucleus of the solitary tract, the dorsal motor nucleus of the vagus nerve, the locus coeruleus, and the Barrington's nucleus. RESULTS: Compared to baseline, sham stimulation did not change phasic gastric, colonic or rectal motor activity. Unilateral subthalamic stimulation increased colonic phasic motility (P<0.05) compared to baseline and the OFF period with no change in gastric and rectal motility. Pre-treatment with atropine, or specific D1 and D2 receptors antagonists prevented the rise in colonic motor activity. An increase in c-Fos protein-positive cells within all the studied nuclei was observed in the stimulated group compared to the sham group. CONCLUSIONS: Unilateral subthalamic stimulation impacts on gut motility in anesthetized rats with a significant increase in colonic motility probably via the modulation of several brain centers. These findings warrant further confirmation in parkinsonian rat models before being transposed to clinical conditions.

Superior interhemispheric approach for midline meningioma from the anterior cranial base.

BACKGROUND: For suprasellar meningioma, the fronto-basal exposure is considered the standard approach. The superior interhemispheric (IH) approach is less described in the literature. OBJECTIVE: To assess the surgical complications, functional outcome (visual, olfaction), morbidity and mortality rates and late recurrence, after resection by superior IH approach of midline skull base meningioma. METHODS: Between 1998 and 2008, 52 consecutive patients with midline meningioma on the anterior portion of the skull base (mean age: 63.8 ± 13.1; sex ratio F/M: 3.7) were operated on via the superior IH approach. After a mean follow-up of 56.9 ± 32.9 months, an independent neurosurgeon proposed a prospective examination of functional outcome to each patient, as well as a visual and olfactory function assessment. RESULTS: Fifty-two patients were divided into a group with olfactory groove meningioma (n=34) and another with tuberculum sellae meningioma (n=18). The outcome was characterized by postoperative complications in 13 patients (25%), mortality rate in two (3.8%) and long-term morbidity at in 17 (37%) of 50 surviving patients. Based on multivariate analysis, no prognosis factor was significant as regards the favorable outcome. The mean postoperative KPS score (86.6 ± 9.4) was significantly improved. However, dysexecutive syndrome was observed in four patients (8%), hyposmia-anosmia in 34 (68%) and visual acuity deteriorated in one (2%). CONCLUSION: The superior IH approach could be considered a safe anteriorly orientated midline approach for removal OGM and TSM meningioma.

[Polyostotic fibrous dysplasia of the thoracic spine. A case study and review of the literature]. / Dysplasie fibreuse polyostotique du rachis dorsal. Cas clinique et revue de la littérature.

Polyostotic fibrous dysplasia of the thoracic spine is extremely rare and considered a benign disease. We report the case of a 46-year-old woman admitted to the emergency department for subacute paraplegia. The spinal X-ray showed a spontaneous fracture at the T4-T5 level. The CT scan revealed a tumor infiltration of the vertebral body responsible for lysis. Spinal MRI confirmed the neoplasia also located in the epidural space with spinal cord compression. The patient underwent an emergency laminectomy associated with transpedicular screw fixation between the T2 and T6 levels. At 2 months, she had evolved to a normal gait. In the second session, a transthoracic approach was used for a bone-graft-assisted fusion procedure to achieve long-term stabilization. At 4 years, the bone fusion was excellent and the patient was able to resume socioprofessional activities. The diagnosis of fibrous dysplasia is usually made histologically on surgical biopsy but MRI and CT scan sometimes provide a preliminary indication. Although a consensus for management of this disease has not been achieved, the authors recommend radical removal of all involved tissues accompanied by internal fixation and bone-graft-assisted fusion.

Simultaneous suprasellar and pineal germ cell tumors in five late stage adolescents: endocrinological studies and prolonged follow-up.

Primary germ cell tumors (PGCT) of the central nervous system usually develop in the third ventricle area, and most frequently in the pineal region. The suprasellar region is the second preferential site for development of these tumors which are rarely simultaneously present in these two sites. We report five new cases of PGCT with pineal and suprasellar localizations, which appeared in late puberty in four boys and one girl aged 17-19 years. The clinical picture associated signs of intracranial hypertension, convergence and verticality palsies, diabetes insipidus and pituitary deficiency. Encephalic MRI revealed a double localization. Endocrine tests revealed a particular pattern associating central diabetes insipidus and a hypothalamic-pituitary disconnection syndrome. Following identification of the pathological type of lesions via a neurosurgical approach, treatment was based on a combined method using chemotherapy, radiotherapy and hormone replacement. Based on this treatment, prolonged remissions were obtained with a good quality of life.

[Radiation-induced cavernoma of the central nervous system]. / Cavernome radio-induit du système nerveux central. A propos d'un cas.

Central nervous system radiation-induced cavernoma (RIC) is a rare entity. We report one case with a review of the literature. This case illustrates the following features: mean age of 11.7 years at time of radiation and mean latency period of nine years for these RIC, which are often numerous (38%), and located in the field of the craniospinal radiation therapy. This nosological entity belongs to the spectrum of radiation-induced lesions, and requires a long-term MRI follow up in patients who underwent cranial radiation therapy.

[Pineal cyst: usefulness of endoscopic treatment]. / Kyste épithélial de la région pinéale: intérêt de la fenestration endoscopique.

Glial cysts of the pineal gland are usually benign and asymptomatic. They develop from the pineal parenchyma and contain liquid. The diagnosis is made by magnetic resonance imaging. In contrast large cysts can be symptomatic due to compression of the aqueduct of Sylvius, compression of the midbrain tectum or mass effect in the posterior fossa. We report the case of a symptomatic cyst treated by an endoscopic procedure.

[Spontaneous supratentorial cerebral hemorrhage: role of surgical treatment]. / Hémorragie cérébrale supratentorielle spontanée: quelle place pour un traitement chirurgical?

Until very recently, no specific therapies have been demonstrated to improve outcome after spontaneous intracerebral haemorrhage (ICH). The STICH (surgical treatment for intracerebral haemorrhage) study showed no overall benefit from early surgery when compared with initial conservative treatment. In contrast, the stereotactic aspiration technique can be safely performed and in a uniform manner. Despite the reduction of ICH volume, no improvement in mortality and functional result was obtained. Endoscopy is a new therapeutic option for ICH with good results for hematoma removal. Based on these feasibility studies, a randomized control trial regarding this procedure would be required to assess the efficacy of this procedure. Due to the lack of benefit observed in the recent STICH trial, emergency surgical evacuation should be reserved for patients with large lobar haemorrhage, mass effect and rapidly deteriorating clinical condition.

[Unruptured intracranial aneurysm: possible therapeutic strategies?]. / Anévrismes intracrâniens non rompus: que proposer?

Intracranial unruptured aneurysm (ICUA) has become a common condition for patient consultation. The mortality rate after fissuration is estimated to be between 52% and 85.7%. The final therapeutic decision results from a balance between the risk of rupture and risks related to the aneurysmal exclusion. Analysis of the risk of rupture risk enables a classification of risk factors. Depending on the circumstances of diagnosis, we considered the ICUA at high risk of rupture for incidental ICUA larger than 7 mm and in the event of associated aneurysms. Classifying by morphologic features, high-risk ICUA were located in the vertebrobasilar system (RR: 4.4; 95%CI: 2.7-6.8), those with a size between 7 and 12 mm (RR: 3.3; 95%CO: 1.3-8.2), larger than 12 mm (RR: 17; 95%CI: 8-36.1), those that were multilobular or a larger size and those ones with a index P/L superior to 3.4 (risk x20). Familial ICUA would expose to a major rupture risk (2 to 7 times sporadic ICUA). Some systemic factors were related to ICUA rupture: arterial hypertension (RR: 1.46; 95%CI: 1.01-2.11) and smoking addiction (RR: 3.04; 95%CI: 1.21-7.66). After microsurgical exclusion, the morbidity and mortality rates were 10% and 2% respectively. Some microsurgical morbidity factors were identified: age (32%>65 years), size (14%>15 mm), vertebrobasilar location and temporary occlusion. The rupture incidence after microsurgical exclusion was estimated 0.26%/year. After endovascular exclusion, the morbidity and mortality rates were 8% and 1% respectively. The complete exclusion rate varied between 47% and 67%. The rupture risk was estimated at 0.9%/year. Treatment recommendations were classified into 3 categories.

Embryology of the internal carotid artery dural crossing: apropos of a continuous series of 48 specimens.

The aim of this study was to describe the embryologic and foetal development of the anterior paraclinoid region and more precisely the relationship of the internal carotid artery to the dura mater. This has been done by examining a collection of histological sections, representing a continuous series of 48 embryologic and foetal specimens, covering the period of the first 6 months of intra-uterine life. Neurological and vascular elements develop during the embryologic period; the internal carotid artery is recognizable in the various sections of its course and acquires a histological adult parietal constitution. The foetal period corresponds to the development of the meningeal structures. The superior, medial and lateral walls appear on the fifteenth week of amenorrhoea and do not change after that. The internal carotid artery enters subarachnoid space accompanied by a sleeve of mesenchymatous cells, which fixes it to the anterior clinoid process. The constitution of this sleeve, arising from the superior wall of the lateral sellar compartment, remained independent of the principle vascular part, which allows the formation of a plan of cleavage. The foetal relations of the dura mater and the internal carotid artery were seen to be different from those of adult subjects described in the literature, suggesting an existence of period of maturation postnatally.