Delayed increase of astrocytic aquaporin 4 after juvenile traumatic brain injury: possible role in edema resolution?

Traumatic brain injury (TBI) is one of the leading causes of death and disability in children and adolescents. The neuropathological sequelae that result from TBI are a complex cascade of events including edema formation, which occurs more frequently in the pediatric than the adult population. This developmental difference in the response to injury may be related to higher water content in the young brain and also to molecular mechanisms regulating water homeostasis. Aquaporins (AQPs) provide a unique opportunity to examine the mechanisms underlying water mobility, which remain poorly understood in the juvenile post-traumatic edema process. We examined the spatiotemporal expression pattern of principal brain AQPs (AQP1, AQP4, and AQP9) after juvenile TBI (jTBI) related to edema formation and resolution observed using magnetic resonance imaging (MRI). Using a controlled cortical impact in post-natal 17 day-old rats as a model of jTBI, neuroimaging analysis showed a global decrease in water mobility (apparent diffusion coefficient, ADC) and an increase in edema (T2-values) at 1 day post-injury, which normalized by 3 days. Immunohistochemical analysis of AQP4 in perivascular astrocyte endfeet was increased in the lesion at 3 and 7days post-injury as edema resolved. In contrast, AQP1 levels distant from the injury site were increased at 7, 30, and 60 days within septal neurons but did not correlate with changes in edema formation. Group differences were not observed for AQP9. Overall, our observations confirm that astrocyticAQP4 plays a more central role than AQP1 or AQP9 during the edema process in the young brain.

A potential catastrophic trap: an unusually presenting sellar lesion.

A 63-year-old man was admitted to our emergency unit complaining headache, vomit and vertigo. A MR of the brain showed an expanding lesion within the sellar region. A subsequent angio-MR excluded any intracranial vascular malformations. Surprisingly, a cerebral angiography performed later on the basis of worsening of neurological signs and symptoms, demonstrated an aneurysm of the internal carotid artery. At the best of our knowledge, this is the first case of a thrombosis of an intracavernous carotid aneurysm mimicking a pituitary apoplexy documented by MR and angio-MR. The treatment of a milder syndrome of pituitary apoplexy is still controversial. This case would favour conservative treatment opposed to surgery at least when an intracavernous extension or invasion of the adenoma would limit the opportunity of a complete tumour removal.

Skin-derived stem cells transplanted into resorbable guides provide functional nerve regeneration after sciatic nerve resection.

The regeneration in the peripheral nervous system is often incomplete and the treatment of severe lesions with nerve tissue loss is primarily aimed at recreating nerve continuity. Guide tubes of various types, filled with Schwann cells, stem cells, or nerve growth factors are attractive as an alternative therapy to nerve grafts. In this study, we evaluated whether skin-derived stem cells (SDSCs) can improve peripheral nerve regeneration after transplantation into nerve guides. We compared peripheral nerve regeneration in adult rats with sciatic nerve gaps of 16 mm after autologous transplantation of GFP-labeled SDSCs into two different types of guides: a synthetic guide, obtained by dip coating with a L-lactide and trimethylene carbonate (PLA-TMC) copolymer and a collagen-based guide. The sciatic function index and the recovery rates of the compound muscle action potential were significantly higher in the animals that received SDSCs transplantation, in particular, into the collagen guide, compared to the control guides filled only with PBS. For these guides the morphological and immunohistochemical analysis demonstrated an increased number of myelinated axons expressing S100 and Neurofilament 70, suggesting the presence of regenerating nerve fibers along the gap. GFP positive cells were found around regenerating nerve fibers and few of them were positive for the expression of glial markers as S-100 and glial fibrillary acidic protein. RT-PCR analysis confirmed the expression of S100 and myelin basic protein in the animals treated with the collagen guide filled with SDSCs. These data support the hypothesis that SDSCs could represent a tool for future cell therapy applications in peripheral nerve regeneration.

A retrospective evaluation of rigid fixation in orthognathic surgery using a biodegradable self-reinforced (70L:30DL) polylactide.

OBJECTIVE: This study was designed to evaluate clinical and radiological evidence of osteotomy site healing in orthognathic surgery after rigid fixation using a biodegradable plating system. STUDY DESIGN: A follow up of 30 patients who underwent orthognathic surgery using a biodegradable self-reinforced (70L:30DL) polylactide plating system was presented. The follow-up schedule for all patients consisted of regular appointments at 1-180 days after surgery. Clinical evaluation involved notation of any abnormal swelling, infection, discoloration, or discharge at the osteotomy sites. Stability was evaluated by manual palpation. For radiographic evaluation, panoramic radiographs were taken immediately after surgery, and again at 7-180 days. The radiographs were analyzed for any visual changes in osteotomy fragments, resorptive changes in osteotomy fragments, callus formation, and union of the osteotomy segments. RESULTS: No clinical complications and no radiological changes in the osteotomy sites were observed. Regarding the clinical usefulness of the biodegradable fixation system, fixation at the time of operation was considered as excellent in all 30 cases. CONCLUSIONS: The conclusions of this study were that self-reinforced (70L:30DL) polylactide was considered to be comparable to other forms of rigid internal fixation for orthognathic surgery.

Long-term evaluation of arthroscopic discectomy of the temporomandibular joint using the Holmium YAG laser.

PURPOSE: The goal of this study was to evaluate the clinical results with arthroscopic discectomy using a Holmium YAG laser for treatment of patients with pain and dysfunction and large disc perforations resulting by advanced internal derangement. PATIENTS AND METHODS: The subjects comprised 30 patients (38 joints) who underwent arthroscopic discectomy with Holmium YAG laser. All patients had chronic pain, restricted range of motion, and a diagnosis of disc perforation (Wilkes stage IV to V of internal derangement). All patients had not responded to conventional nonsurgical treatment (eg, appliance therapy, nonsteroidal anti-inflammatory drugs, physical therapy) or previous temporomandibular joint (TMJ) arthroscopy. All patients filled out a questionnaire preoperatively and postoperatively for assessment of their signs and symptoms. The questionnaire consisted of a visual analog scale (VAS) with items on pain and diet. RESULTS: The overall success rate for arthroscopy discectomy using a Holmium YAG laser was 93.33% (28 of 30 patients) in a mean follow-up of 31.7 months. No complications were observed in this study. Maximal interincisal opening improved from a mean of 25.40 to 39.96 mm after 18 months or more from surgery. The subjective data elicited from VAS scores showed a significant improvement in pain score, in interference of pain with normal diet, and effect of pain on life in general. All preoperative scores were significantly different from postoperative scores (P <.05). CONCLUSIONS: On the basis of this follow-up study, arthroscopic discectomy for treatment of large disc perforations seems to provide an effective treatment for TMJ pain and dysfunction, decreasing the pain and improving the range of motion.

Brain oxygen tension, oxygen supply, and oxygen consumption during arterial hyperoxia in a model of progressive cerebral ischemia.

We investigated the changes in brain oxygen tension (ptiO2) after ventilation with pure O2 in order to (1) clarify the pathophysiology of O2 exchange in the cerebral microcirculation; and (2) investigate the relationship between brain O2 tension, O2 delivery, and consumption in steady-state conditions during stepwise cerebral blood flow (CBF) reductions. A swine model was developed to reduce CBF in three stable steps: (1) baseline (CBF 100%), (2) CBF of 50-60% of baseline, and (3) CBF of <30% of baseline. CBF was reduced by infusing saline into the left lateral ventricle through a catheter connected with an infusion pump. At each step, hyperoxia was tested by increasing the inspired oxygen fraction up to 100%, PtiO2 reflected the CBF reductions, since it was respectively 27.95 (+/-10.15), 14.77 (+/-3.58), and 3.45 (+/-2.89) mm Hg during the three CBF steps. Hyperoxia was followed by an increase in ptiO2, although the increase was significantly lower when hyperoxia was applied during progressive ischemia. O2 supply to the brain did not change during hyperoxia. Arteriovenous oxygen difference (AVDO2) decreased during the phases of intact CBF and moderate impairment, but not during the phase of severe CBF reduction. In conclusion, ptiO2 reductions closely reflect the imbalance between oxygen delivery and demand; this implies a link between low ptiO2 and defective O2 supply due to impaired CBF. However, this relation is not necessarily reciprocal, since manipulating brain oxygen tension does not always influence brain oxygen delivery, as in the case of ventilation with pure oxygen.

Shoulder-hand syndrome in neurosurgical patients treated with barbiturates. A long term evaluation.

OBJECTIVES: To assess the incidence of shoulder-hand syndrome (SHS) in neurosurgical patients (head injuries, intracranial ruptured aneurysms and intracranial meningiomas), treated with barbiturates. SHS is a chronic condition characterized by intense tenderness and functional impairment affecting one hand, the shoulder or both. Barbiturates have been identified as cause of SHS, although there is controversial evidence on the incidence of this disorder in patients started on long-term Phenobarbital (PB) therapy. METHODS: One hundred and twenty-six neurosurgical patients, treated with barbiturates, and a control group of 108 patients, treated with carbamazepine or phenytoin, were enrolled. Both groups were followed up for at least 24 to 36 months. RESULTS: Thirty-five PB-treated patients (27.6%) experienced SHS. In these patients SHS developed during the first 7 months of therapy and regressed after PB discontinuation or, in 2 cases, after dosage reduction. None of the patients in the control group developed SHS. CONCLUSIONS: The occurrence of SHS in the study group was much more common than that reported previously. This higher incidence should depend upon the coexistence of separate risk factors such as age over 50 years, surgery and intracranial pathology. Early diagnosis and rapid withdrawl of treatment are important for symptomatic relief and full functional recovery.

Combined treatment of fourth ventricle ependymomas: report of 26 cases.

BACKGROUND: This study investigated the relevance of prognostic factors and the impact of histological features in posterior fossa ependymoma. METHODS: The charts of 26 patients (aged 1-59 years, mean 20.6 years; 11 adults) with posterior fossa ependymoma operated on between January 1983 and December 1994 were reviewed and patients followed up (mean: 93 months). RESULTS: Gross total resection was performed in 18 patients (69%), subtotal in seven patients (27%), biopsy in one patient (4%). One patient (3.8%) developed respiratory complications and died. All patients underwent posterior fossa radiotherapy (5000 cGy) after surgery. Four children first received chemotherapy and then radiotherapy only when at least 3 years old. Eleven patients (42%) received radiotherapy and subsequently chemotherapy. The 5-year survival rate was 90% for adults and 40% for children (

Oxygen delivery and oxygen tension in cerebral tissue during global cerebral ischaemia: a swine model.

UNLABELLED: Interest in tissue oxygen (PtiO2) monitoring is increasing. However the exact interactions between ptiO2, systemic and cerebral variables are a matter of debate. Particularly, the relationship between ptiO2, cerebral oxygen supply and consumption needs to be clarified. We designed a model to achieve progressive Cerebral Blood Flow (CBF) reduction through 3 steps: 1. baseline, 2. CBF between 50-60% of the baseline, 3. CBF < 30% of the baseline. In 7 pigs, under general anaesthesia, Cerebral Perfusion Pressure (CPP) and CBF were reduced through the infusion of saline in a lateral ventricle. PtiO2 and CBF were monitored respectively through a Clark electrode (Licox, GMS) and laser doppler (Peri-Flux). Blood from superior sagittal sinus and from an arterial line was simultaneously drawn to calculate the artero-venous difference of oxygen (AVDO2). Brain oxygen supply was calculated by multiplying relative CBF change and arterial oxygen content. PtiO2 reflected CBF reductions, as it was 27.95 (+/- 10.15) mmHg during the first stage of intact CBF, declined to 14.77 (+/- 3.58) mmHg during the first CBF reduction, declined to 3.45 (+/- 2.89) mmHg during the second CBF reduction and finally fell to 0 mmHg when CBF was completely abolished. CBF changes were also followed by a decline in O2 supply and a parallel increase in AVDO2. CONCLUSION: This model allows stable and reproducible steps of progressive CBF reduction in which ptiO2 changes can be studied together with oxygen supply and consumption.

Brain oxygen tension during hyperoxia in a swine model of cerebral ischaemia.

UNLABELLED: Arterial hyperoxia improves oxygen tension measured into the cerebral tissue (ptiO2). The extent of this improvement in ameliorating O2 delivery to the cerebral tissue, when cerebral blood flow (CBF) is reduced, is still unclear. The present experiment was developed to investigate the effect of arterial hyperoxia at normal or reduced CBF (baseline, CBF = 50-60%, and CBF = 20-30% of the baseline). CBF reduction was achieved in 7 pigs by saline infusion in a lateral ventricle. PtiO2 was measured by Licox equipment. Arterovenous oxygen difference (AVDO2) was calculated as the difference between arterial oxygen content and superior sagittal sinus oxygen content. Hyperoxia was induced by increasing inspired oxygen fraction to 100%. PtiO2 moved respectively from 27.95 (+/- 10.15) to 45.98 (+/- 15.31), from 14.77 (+/- 3.58) to 30.71 (+/- 12.2), and from 3.45 (+/- 2.89) to 11.1 (+/- 12.6) mmHg at normal CBF, after the first reduction and after the second reduction. O2 supply showed only a negligible increase. AVDO2 decreased during the phases of intact and moderate CBF impairment, while it did not change during the phase of severe CBF impairment. IN CONCLUSION: an increase of ptiO2 does not necessarily correspond to an improvement of brain oxygen delivery. The small increase in oxygen delivery due to hyperoxia may cause a slight improvement in the balance between O2 delivery and consumption during mild CBF reduction, but such improvement is negligible when severe CBF reduction occurs.

Mass volume measurement in severe head injury: accuracy and feasibility of two pragmatic methods.

OBJECTIVE: To assess the clinical feasibility and the accuracy of two pragmatic methods in comparison with a conventional computer based method of measurement of masses from CT. METHODS: Nineteen CT scans of 11 patients with severe head injury, showing 34 traumatic lesions, were examined. The volume of every lesion was digitally measured, then a panel of three examiners independently repeated the measurement using the ellipsoid and the Cavalieri method in random order. RESULTS: All the lesions were identified by all the readers and the mean volume measured by each examiner differed by less than 1.5 ml. The average reading time for each scan was 4 minutes for the ellipsoid and 7 minutes for the Cavalieri method. The average volume of the lesions was 34.2 (SD 35) ml with the digital system, and 38.4 (SD 41) ml and 34.8 (SD 36) ml for the ellipsoid and the Cavalieri readings respectively. The average difference between the applied technique and the digital system was 0.57 (SD 9.99) ml for the Cavalieri direct estimator and 0.20 (SD 15.48) ml for the ellipsoid method. The 95% confidence interval for this difference fell between -2.75 and 3.89 ml for the Cavalieri, and between -4.94 and 5.35 ml for the ellipsoid method. There were 19 lesions >25 ml; the ellipsoid method identified 16 of them, whereas 17 were classified with the Cavalieri method. When considering individual lesions rather than the average volume, discrepancies were detected with both methods. The ellipsoid method was less precise, especially when extracerebral lesions were measured. CONCLUSIONS: Both pragmatic methods are inferior to computer based reading, which is the choice when accurate volume estimation is necessary. However, if a digital volumetric determination of the lesions using a CT computer is not possible, the two pragmatic methods offer an alternative.

Mortality and morbidity in patients operated on for ruptured intracranial aneurysms.

It is generally agreed, mortality and morbidity rates, in patients operated on for ruptured intracranial aneurysm, strictly depend upon the state at admission. Nevertheless, a precise definition of surgical mortality is still not available. Even the term morbidity still remains rather controversial for the lack of accurate evaluation scales. The wide range of parameters, affecting the composition of sample and outcome of patients, such as age, blood at CT scan and atherosclerosis at angiography, makes harder a correct statistical analysis of mortality and morbidity. Moreover, the gap between bleeding and admission, the management and choice of treatment, the selection of unicentric or multicentric studies, the level of the hospital introduce even more striking bias errors. Recent papers reported concrete improvements obtained by means of both aggressive therapeutical behaviour and adequate intensive care management. Among factors, producing improvement of the overall outcome, have to be also reported the encouraging preliminary results supplied by the interventional neuroradiological techniques. However, the overall mortality rate of SAH remains high. Thus, a coded scheme for detection and prevention of risk factors significatively associated to mortality and outcome can be only worked out by employing an appropriate therapeutical behaviour and an adequate intensive care management. Furthermore, employment of feasible evaluation scales will be essential to point out the most accurate procedure for management and treatment of patients with intracranial ruptured aneurysm. We think CESE, developed by one of the authors, to be considered as an adequate method for the assessment of results at follow-up.

Transcallosal approach to tumors of the third ventricle. Surgical results and neuropsychological evaluation.

A series of 34 patients with tumours of the third ventricle were operated on by a transcallosal route. Basal extrinsic lesions compressing or invading the ventricle as well as tumours located in the pineal area were excluded from this review. Tumours were approached by a transforaminal entry in 16 cases (47%), by an interforniceal route in 11 (32%), by a subchoroidal entry in 4 (14%) and by a combined transforaminal and subchoroidal entry in 3 (9%). Four out of 34 patients were submitted to a second operation, through the same approach corridor: 2 for an incomplete removal of an intrinsic tumour and 2 for a late regrowth. Postoperative mortality rate accounted for 5.8% (2 patients). Major post operative complications were hemiparesis (4 patients) and diabetes insipidus (4 patients), that were transient in 3. Akinetic mutism like status was observed in only 1 patient. Postoperative psychic disturbances were noticed in 5 cases. Nine out of 21 patients (62%) with preoperative hydrocephalus required a permanent CSF shunt. Histology revealed that 21 tumours (62%) were intraaxial (4 pilocitic astrocytoma, 10 low grade glioma, 1 giant cell astrocytoma, 1 subependymoma, 4 ependymoma/ependymoblastoma, 1 neurocitoma) and 13 (38%) were extraaxial (8 colloid cyst, 2 craniopharingioma, 1 ectopic pituitary adenoma, 1 lymphocytic hypophysitis and 1 metastasis). Total excision of third ventricle tumours was achieved in all patients with extraaxial tumours and in 62% and 71% of intraaxial tumours with the first and second surgical procedure respectively. Ten out of 34 patients of this series were submitted to a complete neuropsychological evaluation at an interval of 2-9 years after surgery. Memory tests were pathological in 2. Disconnection signs were constantly absent. Control function were preserved. Transcallosal approach remains the best microsurgical method of third ventricle tumours treatment. This route provides the capability for a superior visualization of the entire cavity of the third ventricle through different corridors. Permanent neurological and neuropsychological deficits are not frequent. Epilepsy, that accounted for 28% in patients submitted to transcortical transventricular approach to third ventricle tumours, was never noticed in this series operated on through a transcallosal route.

Functional MRI: primary motor cortex localization in patients with brain tumors.

PURPOSE: Our goal was (a) to test the ability of functional MRI (fMRI) to localize the hand primary motor cortex in patients with brain neoplasms using a conventional scanner and (b) to compare within the same subject the location and morphology of the activated motor areas in the affected hemisphere with the contralateral ones. METHOD: Seventeen right-handed patients with frontoparietal intra- and extraaxial tumors were studied. Hand motor performance ranged from normal to slight impairment of finger dexterity. The fMRI study was based on a series of FLASH images. Two or three contiguous slices parallel to the bicommissural plane were acquired through the level of frontoparietal cortex. Each patient was requested to perform with each hand a finger-tapping task or a simpler repetitive flexion-extension of the last four fingers. Pseudo-color activation maps were then calculated by a Z-score method and superimposed on high resolution images. RESULTS: Five patients were excluded because of gross motion artifacts. In all other patients, areas of significant signal increase were detected on the precentral gyrus. They had a spot-like appearance, and no substantial side-to-side differences in shape or extension could be observed. In the presence of severe compression of the gyri, a displacement of the activated areas in the affected hemisphere with respect to the contralateral ones was noticeable. CONCLUSION: fMRI localization of the primary motor area using a conventional scanner can be obtained also in patients with brain tumors, although with a lower success rate than in normal volunteer studies, mainly because of subject compliance problems. Areas of significantly increased signal are detectable even in cortex where normal anatomical patterns are lost.

Early postoperative seizures and endovenous phenytoin. Preliminary clinical data.

Early seizures represent a major complication in the post operative course of patients operated on for supratentorial tumors or AVMs. The real effectiveness of the AEDs prophylaxis to reduce the occurrence of post operative seizures is controversial. We proposed a prophylactic treatment with endovenous PHT consisting of two infusions of PHT (mean dosage of 18 mg/kg; mean time of 1 hr) perioperatively and during the first postoperative day. The interruption of the previous oral anticonvulsant treatment is not required. The endovenous route should permit a rapid reach of the therapeutical range. Sixty-six patients were treated. Fifty-one patients received two infusions and 15 patients only one infusion. The serum concentration of PHT performed at 24 hrs of operation was in most of patients (more than 80%) in the lower part of the therapeutical range while at 24 hrs of the second infusion was in the higher part or over the range. The overall prevalence of seizures was 10.6%. In the first group the incidence was 7.8%, in the second one was 20%. All the seizures appeared within 48 hrs of the operation. All the patients in the first group had single seizures, 2 patients of the second one experienced two seizures. No status epilepticus was observed. Alteration of consciousness and mild hypotension were the most common side effects. They never required major measurements and were mild, transient and completely reversible. We are starting with a randomized study based on a larger sample of patients which will allow a more reliable statistical analysis.

Postoperative pain in neurosurgery: a pilot study in brain surgery.

The incidence, magnitude, and duration of acute pain experienced by neurosurgical patients after various brain operations are not precisely known, because of a lack of well-designed clinical and epidemiological studies. We assessed these important pain variables in 37 consecutive patients who underwent various brain neurosurgical procedures. Postoperative pain was more common than generally assumed (60%). In two-thirds of the patients with postoperative pain, the intensity was moderate to severe. Pain most frequently occurred within the first 48 hours after surgery, but a significant number of patients endured pain for longer periods. Pain was predominantly superficial (86%), suggesting somatic rather than visceral origin and possibly involving pericranial muscles and soft tissues. Subtemporal and suboccipital surgical routes yielded the highest incidence of postoperative pain. Age and sex were significantly associated with the onset of pain, with female and younger patients reporting higher percentages of postoperative pain. Psychological Minnesota Multiphasic Personality Inventory profiles of patients with and without pain significantly differed on the Hypochondriasis scale, with patients without pain scoring unexpectedly higher than patients with pain. It is possible that hypochondriasis serves as a defense mechanism against pain, at least in some patients. Results of this pilot study indicate that postoperative pain after brain surgery is an important, although neglected, clinical problem, that deserves greater attention by surgical teams, to provide better and more appropriate treatment.

Central nervous system trans-synaptic effects of acute axonal injury: a 1H magnetic resonance spectroscopy study.

N-acetylaspartate (NAA) has previously been proposed as a neuronal marker. 1H magnetic resonance spectroscopy (MRS) is able to detect NAA in brain, and decreases of NAA have been documented after brain injury. The reason for this decrease is not fully understood and neuron loss damage and "dysfunction" have all been proposed. It is hypothesized that acute central nervous system (CNS) deafferentation causes a trans-synaptic NAA decrease and that high resolution 1H MRS is able to detect such a decrease. To test this hypothesis, an experimental model was used in which axonal lesions were obtained by stretch injury in guinea pig right optic nerve (95-99% crossed fibers). The trans-synaptic concentration of NAA, total creatine (Cr), and the NAA/Cr ratio in lateral geniculate bodies (LGB) and superior colliculi (SC) sample extracts were measured 72 h later by high resolution 1H MRS. In the left LGB/SC, which is where right optic nerve fibers project, reductions of NAA and NAA/Cr were found whereas Cr levels were normal. NAA, NAA/Cr, and Cr values were all normal in the right LGB/SC. Histology and EM findings revealed no abnormalities. At 7 days, left LGB/SC NAA and NAA/Cr values were in the normal range. It was concluded that 1) acute deafferentation in the CNS causes a trans-synaptic decrease of NAA levels that can be detected by 1H MRS and 2) NAA decrease may be due to changes of NAA metabolism caused by functional neuronal inactivity rather than neuronal loss, injury or "dysfunction." 1H MRS is a potential tool for the study of functional effect of CNS lesions in vivo.

Long-term outcome in aqueductal stenosis.

In this study, 78 patients with aqueductal stenosis were submitted to detailed neurodevelopmental assessment with a follow-up of 5-25 years. Sixty-eight percent of patients were categorized as normal; they either attended normal school courses or had regular jobs. Among these, 34% had some motor abnormalities (ataxia, mild hemiparesis, visual disturbances). Twenty-four percent (19 cases) were moderately disabled (trainable retardation) and 8% (6 cases) were severely handicapped. Epilepsy was observed in 13% of the cases. Incidence of recurrent and generalized seizures paralleled neurodevelopmental outcome (5% in normal, 16% in moderately disabled and 50% in severely disabled patients). Endocrine dysfunctions were evident in 28% of the cases and were characterized by precocious or delayed puberty, amenorrhea and somatic underdevelopment. No patient with ventricular enlargement and a cortical mantle width below 20 mm showed a good outcome. Large ventricles were compatible with normal mental development when compensated with a corresponding cranial vault enlargement. In patients with normal mental status and motor abnormalities, long-term CT scan findings revealed the presence of focal brain abnormalities (poroencephaly, brain atrophy, calcifications, extracerebral collections).