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Biomedical subjects

D C Wright

Publications and source records attributed to D C Wright.

At least 37 records · Page 2Linked to original sources

The petrolingual ligament: the anatomy and surgical exposure of the posterolateral landmark of the cavernous sinus.

The petrolingual ligament is the posteroinferior attachment of the lateral wall of the cavernous sinus, where the internal carotid artery enters the cavernous sinus. The petrous segment of the internal carotid artery finishes and the cavernous segment begins at the superior margin of this ligament. The ligament is surgically important due to its identification as a landmark for dissection of the internal carotid artery during the approaches to posterolateral intracavernous and extracavernous lesions. It can be well exposed after mobilization of the gasserian ganglion, or after the trigeminal root and ganglion have been split along the junction of V2 and V3 (the transtrigeminal approach). The petrolingual ligament was studied in five cadaveric head specimens from ten sides. The size of the ligament was measured, and its anatomical, clinical and surgical importance is discussed.

Carotid Artery, Internal↗

An increase in extracellular glutamate is a sensitive method of detecting ischaemic neuronal damage during cranial base and cerebrovascular surgery. An in vivo microdialysis study.

All patients undergoing neurological surgery are at risk for serious complications. Ischaemic damage presenting with hemiparesis or speech difficulties occurs in up to 6% of patients undergoing cerebral bypass procedures and other complicated neurosurgical procedures. Currently available methods for detection of such damage include the use of somatosensory evoked potentials (SSEPs) and electro-encephalography (EEG). Unfortunately, these techniques have false positives and may remain normal in the presence of severe focal neurological deficits. Early detection of potential deficits may prevent or minimize damage through a change in operative or anaesthetic strategy. With the availability of several potential neuroprotective compounds, it is also possible to treat patients at risk of developing ischaemic complications if the individuals are identified early. The excitatory neurotransmitter glutamate is not only a metabolic product, but is also thought to promote ischaemia induced cell injury if released into the extracellular space. It may be a significant parameter for ischaemic brain metabolism. In this report we describe 10 patients who underwent extracranial-intracranial (EC-IC) high flow bypass procedures with routine intra-operative monitoring (IOM) as well as intra-operative in-vivo microdialysis measurement of glutamate. Our aim was to compare intra-operative microdialytic findings and IOM findings with respect to patients' early postoperative clinical courses. Three patients had significant intra-operative glutamate increases indicating ischaemia. Two of these patients awoke with a new neurological deficit (hemiparesis). Routine IOM findings were either normal or showed only transient changes during the time the glutamate levels were high. Our study shows that an increase in extracellular glutamate, as monitored by in-vivo microdialysis, is an excellent early market of neuronal damage. While our glutamate measurements were done off-line, it may be possible to get in future continuous on-line measurements to serve as an early warning system for potential ischaemic damage.

Adult↗

Persistent trigeminal artery: an anatomic study.

INTRODUCTION: The most frequent embryonic communication between the vertebrobasilar and carotid systems is a persistent trigeminal artery (PTA). It has been observed in 0.1 to 0.2% of cerebral angiograms. We found this variation in an anatomic specimen, and after microscopic dissection, we performed an analysis of the course of the PTA and its relationship with the abducens nerve and the meningohypophyseal trunk. METHOD: A PTA was incidentally encountered in an injected cadaver specimen during a transpetrosal approach. This embryonic variation and its anatomic relationship are discussed. RESULTS: The PTA can take either a lateral or medial course regarding its relationship with the abducens nerve. When the PTA originates from the posterolateral aspect of the posterior bend of the cavernous carotid artery (C4 segment), it crosses underneath and distorts the abducens nerve, continuing between the abducens and trigeminal nerves. When taking a medial course, the PTA arises from the posteromedial aspect of the posterior bend of the cavernous carotid at the same segment and pierces the clival dura at the dorsum sellae. Cranial nerve displacement or distortion is less likely in this variation. In an analysis of carefully described anatomic studies, the PTA and meningohypophyseal trunk were found arising from either common or separated origins. CONCLUSION: The most frequent embryological anastomosis between the carotid and vertebrobasilar system is the PTA. Its course and relationship with the cranial nerves may determine its clinical presentation.

Aged↗

Surgical anatomy of the infratemporal fossa: the styloid diaphragm revisited.

INTRODUCTION: The infratemporal fossa (ITF) gives passage to most major cerebral vessels and cranial nerves. Dissection of the ITF is essential in many of the lateral cranial base approaches and in exposure of the high cervical internal carotid artery (ICA). We reviewed the surgical anatomy of this region. METHODS: Direct foraminal measurements were made in seven dry skulls (14 sides), and the relationship of these foramina to each other and various landmarks were determined. Ten ITF dissections were performed using a preauricular subtemporal-infratemporal approach. Preliminary dissections of the extracranial great vessels and structures larger than 1 cm were performed using standard macroscopic surgical techniques. Dissection of all structures less than 1 cm was conducted using microsurgical techniques and instruments, including the operating microscope. The anatomic relationships of the muscles, nerves, arteries, and veins were carefully recorded, with special emphasis regarding the relationship of these structures to the styloid diaphragm. The dissection was purely extradural. RESULTS: The styloid diaphragm was identified in all specimens. It divides the ITF into the prestyloid region and the retrostyloid region. The prestyloid region contains the parotid gland and associated structures, including the facial nerve and external carotid artery. The retrostyloid region contains major vascular structures (ICA, internal jugular vein) and the initial exocranial portion of the lower Cranial Nerves IX through XII. Landmarks were identified for the different cranial nerves. The bifurcation of the main trunk of the facial nerve was an average of 21 mm medial to the cartilaginous pointer and an average of 31 mm medial to the tragus of the ear. The glossopharyngeal nerve was found posterior and lateral to stylopharyngeus muscle in nine cases and medial in only one. The vagus nerve was consistently found in the angle formed posteriorly by the ICA and the internal jugular vein. The spinal accessory nerve crossed anterior to the internal jugular vein in five cases and posterior in another five cases. It could be located as it entered the medial surface of the sternocleidomastoid muscle 28 mm (mean) below the mastoid tip. The hypoglossal nerve was most consistently identified as it crossed under the sternocleidomastoid branch of the occipital artery 25 mm posterior to the angle of the mandible and 52 mm anterior and inferior to the mastoid tip. CONCLUSION: The styloid diaphragm divides the ITF into prestyloid and retrostyloid regions and covers the high cervical ICA. Using landmarks for the exocranial portion of the lower cranial nerves is useful it identifying them and avoiding injury during approaches to the high cervical ICA, the upper cervical spine, and the ITF.

Arteries↗

Endodermal cysts of the posterior fossa. Report of three cases and review of the literature.

The pathogenesis of endodermal cysts of the posterior fossa is still incompletely understood. The authors reviewed three new cases and those reported in the literature to clarify the clinical, pathological, radiological, and surgical characteristics of these lesions. A total of 49 cases were reviewed. Details on demographic profiles, clinical characteristics, histopathological and radiological features, and surgical methods were collected. These cysts have a predominance in male patients (61%) and can occur at any age (birth-77 years). In patients with posterior fossa endodermal cysts there is a bimodal age distribution and headache is the most frequent complaint. On immunohistopathological examination, endodermal cysts were reactive for epithelial membrane antigen and for keratin immunostains whenever the latter were tested. The cysts were reactive for carcinoembryonic antigen in nine of 11 cases. Endodermal cysts were located anterior to the brainstem in 51% of cases and in the fourth ventricle in 21% of cases. They frequently appeared hypodense on computerized tomography scans, and in five cases, the lesion was missed. The cyst's appearance on magnetic resonance imaging is variable. Resection was complete in 19 cases and partial in 11; marsupialization was achieved in two cases. Three recurrences have been reported. Total excision with preservation of neurological function should be the goal. Cranial base approaches are helpful for surgical access in selected examples of these lesions.

Adult↗

Acoustic neuromas: results of current surgical management.

OBJECTIVE: In this article, we review the surgical outcomes of 179 patients with acoustic neuromas. METHODS: Most of the tumors (84%) were operated on using a retrosigmoid, transmeatal approach. A transpetrosal, retrosigmoid approach was used in 10% of the patients, most of whom had large tumors. The translabyrinthine (4%) and transmastoid, transpetrosal, partial labyrinthectomy approaches (2%) were used selectively. The operative approaches are discussed. Tumors were categorized according to their cerebellopontine angle dimensions as small (< 2 cm), medium (2.0-3.9 cm), and large (> or = 4 cm). RESULTS: House-Brackmann evaluation of postoperative facial nerve function revealed excellent results (Grade I or II) in 96% of small tumors, 74% of medium tumors, and 38% of large tumors. A fair postoperative function (Grade III or IV) was achieved in 4% of small tumors, 26% of medium tumors, and 58% of large tumors. Functional hearing preservation, defined as Gardner-Robertson Class I or II, was achieved in 48% of small tumors and 25% of medium tumors. Hearing was not preserved in any of the three patients with large tumors in whom hearing preservation was attempted. Treatment complications consisted mainly of cerebrospinal fluid leakage (15% of the patients). The majority of the patients who experienced cerebrospinal fluid leakage were treated successfully with lumbar spinal drainage; only four patients (2% of the total group) required subsequent surgery for correction of cerebrospinal fluid leakage. There were two deaths (1%) in this series. One death occurred as the result of myocardial infarction and the other as the result of severe obstructive lung disease. One patient sustained disability because of cerebellar and brain stem injury. Complete tumor resection was accomplished in 99% of the patients, and there was no evidence of recurrence in this group. Only 1 of the 179 patients underwent incomplete tumor resection; he required subsequent surgery for symptomatic tumor regrowth. Our patient follow-up had a mean duration of 70 months and a median of 65 months (range, 3-171 mo). CONCLUSION: Our results are similar to those of other large microsurgical series of acoustic neuromas. Unless a patient has major medical problems, microsurgery by an experienced team of surgeons is preferred over radiosurgery.

Adolescent↗

Surgical treatment of meningiomas involving the cavernous sinus: evolving ideas based on a ten year experience.

The outcomes of 114 patients with meningiomas operated at the University of Pittsburgh were analyzed. Cerebrospinal fluid leakage was the most frequent complication, observed in 25 patients (21%). Complications were more frequent in patients who had recurrent (previously operated) tumors and patients with extensive tumors. Our current analysis also indicates that patients with prior radio-therapy (usually external beam) have unacceptably high complication rates after microsurgery. Early results indicate that regrowth rates are much higher in patients with incomplete resection (20%) than those with gross total excision (5%). Of the 114 patients, 108 returned to independent living and/or their previous occupation.

Cavernous Sinus↗

Petroclival and foramen magnum meningiomas: surgical approaches and pitfalls.

The management of petroclival and foramen magnum meningiomas has been revolutionized by the techniques of cranial base surgery. However, these tumors are still among the most difficult cranial base lesions to treat. In this report, we discuss the classification, presenting symptoms, preoperative investigation, treatment indications, operative approaches and technique, postoperative complications and care, and results of surgery of petroclival and foramen magnum meningiomas. Careful analysis of tumor- and patient-related factors has helped us to predict which features can lead to postoperative problems in patients allowing surgeons to appropriately modify their behavior. The application of cranial base techniques-combined with new knowledge about the limitations of microsurgical resection-can greatly reduce postoperative morbidity in these patients.

Cranial Fossa, Posterior↗

Management and long-term outcome of adenoid cystic carcinoma with intracranial extension: a neurosurgical perspective.

Adenoid cystic carcinoma is a tumor of minor and major salivary glands that often invades the cranial base and intracranial cavity via local and perineural spread. In the past, the role of neurosurgeons in managing these tumors has been limited. The growth of interdisciplinary cranial base surgical approaches has now increased the involvement of neurosurgeons in the management of these tumors. We present a series of 16 patients with adenoid cystic carcinomas with cranial base and intracranial extension, the largest series reported in the neurosurgical literature. We have focused our approach on a neurosurgical perspective and made recommendations for the treatment of these tumors in relation to the following specific aspects of this disease. 1) The management of the carotid artery: In our experience, when the carotid artery is involved by tumor, a preliminary cerebral revascularization procedure with a cervical carotid to middle cerebral artery vein bypass graft should be performed before tumor resection. 2) The management of the cavernous sinus and orbit: Cavernous sinus tumor should be removed as fully as possible, but every effort should be made to preserve the IIIrd and IVth cranial nerves to achieve optimal functional and cosmetic results. The orbit should be exenterated when there is intraconal involvement; otherwise, intraorbital tumor can be removed with orbital preservation. 3) The use of palliative surgery: We have found that the use of palliative surgery can be considered even in patients whose extent of local disease precludes a surgical cure. The slow progression of the disease allows for long-term survival of many patients with advanced local disease and even of those with metastatic disease. 4) The long-term survival of these patients: In our series, six patients had no evidence of local disease and a mean survival of 72 months, one living patient had evidence of local disease and has survived 56 months, eight patients died of disease, with a mean survival of 137 months, and one patient died of complications after surviving for 63 months.

Adult↗

Enzyme-linked immunosorbent assay quantification of cytokine concentrations in human meningiomas.

OBJECTIVE: To gain insight into the network of cytokine gene expression in the brain tumor microenvironment, we investigated the presence of the following cytokines in freshly excised brain tumors: interleukin (IL)-1 beta, IL-2, IL-4, and IL-6. METHODS: Tumor specimens from nine meningiomas were grown as tissue explants. The supernatants from the explants were tested for the presence of the aforementioned cytokines via the enzyme-linked immunosorbent assay method. RESULTS: IL-6, which is thought to stimulate acute protein phase synthesis, neovascularization, and cell proliferation, was found in all of the samples in greater concentrations than the other cytokines tested. IL-1 beta, another stimulatory cytokine thought to be involved in acute protein phase synthesis and cell proliferation, was also found in 100% of the samples tested, in concentrations significantly lower than those of IL-6. As expected, the presence of IL-2 and IL-4 was not detectable in any of the samples. CONCLUSION: This study is the first to clearly determine the relative concentrations of IL-1 beta and IL-6, using enzyme-linked immunosorbent assay quantification. These findings are an important precursor to future studies using antibodies to IL-1 beta and IL-6 and antibodies to IL-6 receptors to modulate neoplastic growth both in vitro and in vivo.

Cell Division↗

Long-term follow-up of patients with meningiomas involving the cavernous sinus: recurrence, progression, and quality of life.

OBJECTIVE: In this report, we evaluate the recurrence- and progression-free survival of patients with meningiomas involving the cavernous sinus. METHODS: The rates of tumor recurrence and progression in 119 patients with meningiomas involving the cavernous sinus treated between 1983 and 1993 were analyzed. RESULTS: The mean follow-up period was 33.8 months. There were seven recurrences of completely resected tumors (7 of 73, 10%) and seven progressions of incompletely resected tumors (7 of 46 15%). Life table analysis of recurrence- and progression-free survival was performed. The recurrence-free survival rate was 94% at 3 years and 81% at 5 years. In contrast, the progression-free survival rate was 87% at 3 years and 62% at 5 years (P = 0.0456). There were two patterns of recurrence or progression. The first group of tumors had an aggressive biological behavior with growth at multiple areas of resection; the second group showed growth at or near the margins of resection. Functional status continued to improve slowly during the follow-up period; however, there was no statistically significant difference between the Karnofsky scores obtained 3 to 12 months postoperatively and the follow-up Karnofsky scores (obtained > 1 yr postoperatively). CONCLUSION: Surgery for meningiomas involving the cavernous sinus seems to provide excellent tumor control. Our experience suggests that for the majority of these tumors, complete tumor resection can be performed with acceptable risks of morbidity and mortality and seems to increase the duration of recurrence-free survival. The long-term quality of life of surviving patients is satisfactory, with the great majority of the patients being independent.

Cavernous Sinus↗

Quantification and pharmacokinetics of blood-brain barrier disruption in humans.

Hyperosmolar blood-brain barrier disruption (HBBBD), produced by infusion of mannitol into the cerebral arteries, has been used in the treatment of brain tumors to increase drug delivery to tumor and adjacent brain. However, the efficacy of HBBBD in brain tumor therapy has been controversial. The goal of this study was to measure changes in vascular permeability after HBBBD in patients with malignant brain tumors. The permeability (K1) of tumor and normal brain blood vessels was measured using rubidium-82 and positron emission tomography before and repeatedly at 8- to 15-minute intervals after HBBBD. Eighteen studies were performed in 13 patients, eight with glioblastoma multiforme and five with anaplastic astrocytoma. The HBBBD increased K1 in all patients. Baseline K1 values were 2.1 +/- 1.4 and 34.1 +/- 22.1 microl/minute/ml (+/- standard deviation) for brain and tumor, respectively. The peak absolute increases in K1 following HBBBD were 20.8 +/- 11.7 and 19.7 +/- 10.7 microl/minute/ml for brain and tumor, corresponding to percentage increases of approximately 1000% in brain and approximately 60% in tumor. The halftimes for return of K1 to near baseline for brain and tumor were 8.1 +/- 3.8 and 4.2 +/- 1.2 minutes, respectively. Simulations of the effects of HBBBD made using a very simple model with intraarterial methotrexate, which is exemplary of drugs with low permeability, indicate that 1) total exposure of the brain and tumor to methotrexate, as measured by the methotrexate concentration-time integral (or area under the curve), would increase with decreasing infusion duration and would be enhanced by 130% to 200% and by 7% to 16%, respectively, compared to intraarterial infusion of methotrexate alone; and 2) exposure time at concentrations above 1 microM, the minimal concentration required for the effects of methotrexate, would not be enhanced in tumor and would be enhanced by only 10% in brain. Hyperosmolar blood-brain barrier disruption transiently increases delivery of water-soluble compounds to normal brain and brain tumors. Most of the enhancement of exposure results from trapping the drug within the blood-brain barrier, an effect of the very transient alteration of the blood-brain barrier by HBBBD. Delivery is most effective when a drug is administered within 5 to 10 minutes after disruption. However, the increased exposure and exposure time that occur with methotrexate, the permeability of which is among the lowest of the agents currently used clinically, are limited and the disproportionate increase in brain exposure, compared to tumor exposure, may alter the therapeutic index of many drugs.

Adult↗

Outcomes analysis in cranial base surgery - preliminary results.

A system of analysis addressing predictors of management outcomes in Cranial Base Surgery has yet to be published. We therefore report data on seventy-nine consecutive patients undergoing surgery for tumors involving the cranial base, excluding patients with the diagnosis of pituitary microadenoma. Outcomes were defined prospectively in terms of completeness of tumor resection, complications of treatment with emphasis on neurological morbidity, and return to work or independent living. Also, preoperative features are analyzed as influencing cost of treatment, estimated in terms of the number of surgical procedures required, duration of hospital and Intensive Care Unit stay, and time taken to return to work. Preliminary analysis of data reveals that severe brainstem compression, large tumor size (average diameter > 3 cm), high cavernous sinus grade, and tumor encasement of major cerebral arteries are associated with incomplete tumor resection (p < 0.05). Patient age greater than 65, preoperative Karnofsky Performance Score (KPS) less than 80, and severe brainstem compression are associated with increased risk of stroke (p < 0.05). Age greater than 65 and preoperative KPS less than 80 are associated with an increased length of stay (p < 0.05). Other untoward events did not occur with sufficient frequency to reach statistical significance. A model of outcomes analysis in Cranial Base Surgery is proposed utilizing a database to incorporate a group of non-operated patients and include quality of life measurements in long-term patient follow-up.

Brain Neoplasms↗

Chordomas and chondrosarcomas of the cranial base: results and follow-up of 60 patients.

The management of chordomas and chondrosarcomas involving the cranial base remains controversial. The options for therapy include biopsy, partial resection, radical resection, and various forms of radiotherapy. In this article, we analyze the outcome of 60 patients with cranial base chordoma or chondrosarcoma treated with extensive surgical resection between 1984 and 1993. Forty-six patients had chordomas, and 14 had low-grade chondrosarcomas; 50% of these patients had been treated previously. Preoperative studies included computed tomography, magnetic resonance imaging, cerebral angiography, and balloon occlusion test of the internal carotid artery, as indicated. Magnetic resonance imaging was performed on all patients during follow-up. The surgical approaches used for tumor resection were predominantly the following: subtemporal, transzygomatic, transcavernous, and transpetrous apex; subtemporal and infratemporal; extended frontal; and extreme lateral transcondylar. Staged operations with a combination of approaches were used when necessary (52% of cases) to remove a tumor more completely. Statistical analysis was done by the chi 2 test and correlation matrix. Sixty-seven percent of the patients had total or near-total resection. Twenty percent of the patients received postoperative radiotherapy. Eleven patients died during the postoperative follow-up period, nine with chordomas and two with chondrosarcomas. Three patients died because of systemic complications within 3 months after surgery, five died because of tumor recurrence, one died from unrelated causes, and two died from late complications of radiotherapy. The recurrence-free survival rate for all tumors was 80% at 3 years and 76% at 5 years. Chondrosarcomas had a better prognosis than chordomas (recurrence-free survival rates, 90% at 5 years and 65% at 5 years, respectively; P = 0.09). Patients who had undergone previous surgery had a greater risk of recurrence (5-year recurrence-free survival rate, 64%) than did patients who had not undergone previous surgery (5-year recurrence-free survival rate, 93%; P < 0.05). Patients with total or near-total resection had a better 5-year recurrence-free survival rate (84%) than did patients with partial or subtotal resection (64%) (P < 0.05). Postoperative leakage of cerebrospinal fluid was the most frequent complication (30% of patients) and was found to increase the risk of permanent disability. Patients who had undergone previous radiotherapy had a greater risk of death in the postoperative period (within 3 months of their operations) and during follow-up. However, total or near-total resection did not increase the rate of postoperative disability.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

The results of surgery for benign tumors of the cavernous sinus.

CAVERNOUS SINUS SURGERY has been performed increasingly in the last 2 decades because of new knowledge and technologies. With increasing international expertise in cavernous sinus surgery, the results must be analyzed critically to search for accurate prognosticators of outcome. We performed a retrospective review of 124 patients (40 male, 84 female; mean age, 45 years) who underwent cavernous sinus surgery for benign tumors from 1983 to 1992. Sixty-five percent had tumors encasing the internal carotid artery. Mean follow-up was 29 months (median, 26 mo). Gross total or near-total resection was possible in 80%. Patients with neurilemomas, angiofibromas, epidermoids, chondroblastomas, and hemangiomas were more likely to have total or near-total resection (100% versus 75%, P < 0.025). Disabling complications (five cerebral infarctions, two meningitis, and one hydrocephalus with chiasmal prolapse) occurred only in patients with meningiomas or pituitary adenomas. On follow-up, excellent/good binocular vision was achieved in 53% of patients entering surgery with excellent/good function versus 25% who entered surgery with fair/poor binocular vision (P < 0.025). Ninety-three percent of patients had a Karnofsky score > or = 70 on follow-up. There were a total of 12 recurrences (10%), 6 in patients with meningiomas, 2 in patients with angiofibromas, 2 in patients with craniopharyngiomas, 1 in a patient with a pituitary adenoma, and 1 in a patient with an osteoblastoma. Patients with tumor growth or neurological symptoms indicative of progressive cavernous sinus involvement should undergo cavernous sinus exploration. This surgery has acceptable morbidity and mortality and, if the tumor can be removed easily, the surgeon should try to perform radical tumor resection. To avoid major complications, the surgeon must exercise utmost care to preserve the neurovascular structures of the cavernous sinus, with special attention to tumors that extend into the petroclival region. Better results from surgery can be expected in those patients with neurilemomas, hemangiomas, or epidermoids than in patients with meningiomas, craniopharyngiomas, or pituitary adenomas. Good functional outcome can be expected, particularly if the patient's preoperative clinical status is good. Particular attention must be paid to the reconstruction of anatomic barriers in order to prevent cerebrospinal fluid leakage and subsequent meningitis.

Adult↗

Evaluation of memory, learning ability, and clinical neurologic function in pathogen-free mice with systemic lupus erythematosus.

OBJECTIVE: To determine if neurologic impairment is related to progressive autoimmune disease in 3 murine models of systemic lupus erythematosus (SLE): MRL/lpr, NZB, and NZB/WF1. METHODS: Sensorimotor function, learning, and memory were tested within strains at specific ages, before and after the appearance of SLE. These parameters were also compared between strains for young and older lupus mice and their congenic controls with reduced autoimmune disease (MRL/lpr versus MRL/+; NZB versus NZB/xid). RESULTS: Abnormal neurologic features were present at a much higher frequency in MRL/lpr mice than in age-matched MRL/+ control mice, and sensorimotor function deficits were also seen in NZB/WF1 mice. Strains that develop lupus showed deficits on a water-escape, distal cue discrimination task and on a food-rewarded, proximal cue discrimination task, but the cognitive impairments were not global. CONCLUSION: MRL/lpr, NZB, and NZB/WF1 mice differed in terms of which behaviors were impaired as well as when those impairments appeared.

Age Factors↗