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Wilson disease is a severe genetic disorder associated with intracellular copper overload. The affected gene, ATP7B, has been identified, but the molecular events leading to Wilson disease remain poorly understood. Here, we demonstrate that genetically engineered Atp7b−/− mice represent a valuable model for dissecting the disease mechanisms. These mice, like Wilson disease patients, have intracellular copper accumulation, low-serum oxidase activity, and increased copper excretion in urine. Their liver pathology developed in stages and was determined by the time of exposure to elevated copper rather than copper concentration per se. The disease progressed from mild necrosis and inflammation to extreme hepatocellular injury, nodular regeneration, and bile duct proliferation. Remarkably, all animals older than 9 months showed regeneration of large portions of the liver accompanied by the localized occurrence of cholangiocarcinoma arising from the proliferating bile ducts. The biochemical characterization of Atp7b−/− livers revealed copper accumulation in several cell compartments, particularly in the cytosol and nuclei. The increase in nuclear copper is accompanied by marked enlargement of the nuclei and enhanced DNA synthesis, with these changes occurring before pathology development. Our results suggest that the early effects of copper on cell genetic material contribute significantly to pathology associated with Atp7b inactivation.

Background : The purpose of this study is to compare arc-based and mini-multileaf collimator (mMLC)-based radiosurgery treatment plans using isodose distributions and dose-volume histograms. Methods : Of 11 patients who underwent conventional arc-based radiosurgery for intracranial malignancies, four were treated with one isocenter, four were treated with two isocenters and three were treated with three isocenters. The same cases were re-planned using a test version of mMLC-based radiosurgery software for multiple static non-coplanar fields. Results and conclusion : For non-spherical targets, treatment planning is relatively intuitive with mMLC-based radiosurgery, reducing the amount of time required for planning. Moreover, a lower dose of radiation is delivered to normal tissue with mMLC-based radiosurgery than with arc-based radiosurgery, which theoretically should lead to a reduced risk of complications.

Summary:As the elder population lives longer, symptomatic lumbar stenosis will become a more frequent clinical entity. Once surgical decompression is considered, controversy exists as to when to fuse. In this study, 206 patients with symptomatic lumbar stenosis were treated initially by decompressio

Background: We report the first application of Gamma Knife radiosurgery (GKR) for recurrent glossopharyngeal neuralgia (GN) after microvascular decompression (MVD). The patient is a 51-year-old male with left-sided GN. He underwent MVD and did well for almost 4 years. Later on, the patient started to experience recurrent intolerable throat pain, frequently 10/10 in intensity. Based on the application of radiosurgery for trigeminal neuralgia, GKR was offered to the patient. Methods: After careful identification of the nerve with the assistance of a neuroradiologist, we targeted the nerve root complex, which is the cisternal portion of the nerve, using the Coherent Oscillatory State Acquisition for the Manipulation of Image Contrast (COSMIC) pulse sequence with contiguous 1-mm slices obtained by an 1.5 Tesla MRI. The radiosurgery was planned utilizing the Leksell Gamma Plan version 8.1. A single shot with a 4-mm collimator was used to deliver 80 Gy to the 100% isodose line. Results: Four weeks after the treatment, the patient began to notice significant pain relief. At the 12-month follow-up, the patient’s pain, which was intolerable prior to radiosurgery, was mild and occasional. Conclusion: GKR, which is now widely used for refractory trigeminal neuralgia, can be considered for refractory or recurrent GN. With a multidisciplinary approach and advanced neuroimaging, GKR is feasible for GN after MVD, despite the shortness of the intracranial cisternal nerve portion. Further studies are necessary to establish the role of GKR for refractory GN after MVD; however, given its rarity and the lack of experience with GKR for this condition, retrospective studies with dozens of patients are almost impossible at this time.

Evidence suggests that the Hooper Visual Organization Test (HVOT) has naming and executive components that vary in size depending on neurological diagnosis. The current study used a sample of individuals with Parkinson's disease (PD) to demonstrate for the first time that an executive measure can be the best predictor of HVOT performance. Forty-eight nondemented and nondepressed individuals with idiopathic PD completed the HVOT and other measures of visuoperception, executive function, and visual confrontation naming. Despite average performance on all neuropsychological measures, an executive measure, time to complete Trail-Making Test Part B minus time to complete Part A, was clearly the best predictor of HVOT performance in a standard regression. The pattern of neurocognitive predictors is unlike that reported in healthy individuals and other patient samples. This finding suggests that the presence of a neuropathological process can alter neurocognitive correlates even when performance is intact, and supports the contention that executive function is paramount in the cognitive profile associated with PD.

This article reports the outcomes of 654 consecutive patients treated during a 4.5-year period. Patients had a microdiscectomy, a laminectomy plus microdiscectomy, or a decompressive laminectomy with a microdiscectomy. The causes of ruptured discs were lifting (31.4%), falls (10.2%), and sports (10.0%). Almost all patients had complained of leg pain (99%), and 79% had radicular pain in a dermatomal distribution. Thirty-three percent of the patients had been involved in industrial accidents, and 6% had legal claims pending during the surgical period. Almost 11% of the patients had complications, and there was one death caused by abdominal arterial bleeding. Patients were also rated according to the Prolo Functional-Economic Outcome Rating Scale to improve the ability to compare series in the future. Almost 80% of the patients had good outcomes as defined by scores on this scale of 8 (16.2%), 9 (33.2%), and 10 (26.9%). Several conclusions can be drawn from the results of this series: 1) most patients had good outcomes; 2) patients with nonindustrial injuries had better outcomes than did patients with industrial injuries; 3) professionals with legal concerns and laborers with industrial insurance had good outcomes; and 4) the Functional-Economic Outcome Rating Scale appears to be a useful tool for comparing different procedures more objectively and for comparing the outcomes across series.

Despite the clinical importance of the question, a number of methodological issues have limited firm conclusions regarding the cognitive safety of deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's disease (PD). Amongst these issues, studies have generally failed to consider the postoperative changes that occur within individual patients. This study utilized reliable change indices (RCIs) derived from a PD sample to determine the frequency of clinically significant postoperative decline on a battery of neuropsychological measures. This approach addresses measurement reliability, potential practice effects, and disease progression. The proportion of patients experiencing clinically significant postoperative decline on measures of list learning and verbal fluency was greater than expected based on disease progression; however, the majority of patients (55%) did not experience a significant decline in performance on any of the cognitive tests administered, and only one experienced decline on more than one test. Therefore, the statistically significant declines on measures of list learning and verbal fluency observed in the sample as a whole were the result of clinically significant declines experienced by a minority of participants.

Essential tremor (ET) is increasingly thought to involve a heterogeneous group of patients, with some also exhibiting symptoms of Parkinson's disease (PD), including cognitive deficits. The goal of this study was to utilize a broad battery of neuropsychological measures to compare the cognitive function of 33 ET patients with that of 33 matched PD patients and 21 normal controls. Results indicated that the ET group performed significantly worse than controls across multiple cognitive domains, but performed remarkably similar to PD patients, consistent with frontosubcortical dysfunction.

✓ Although cerebral venous malformations have been reported to cause epilepsy, progressive neurological deficits, and hemorrhage, their clinical significance remains controversial. In an attempt to clarify the natural history of the lesion and suggest an appropriate management strategy, the authors review their experience with 30 patients. In four patients with cerebellar venous angioma, an acute episode of ataxia was documented. The coexistence of a cavernous malformation was pathologically confirmed in the two patients who underwent surgery for bleeding presumed caused by the venous angioma. Infarction was shown in two patients and a tumor in two others. Follow-up periods ranged between 18 and 104 months, with only five patients symptomatic at the time of this report. Rebleeding had not occurred, nor had acute episodes of neurological dysfunction been documented. This clinical experience suggests that a venous malformation is frequently associated with other, more symptomatic conditions and is often erroneously identified as the source of the symptoms. Because the nature of the relationship between the venous malformation and the allied conditions remains ambiguous, it is recommended that patients harboring a “symptomatic” venous malformation undergo high-field magnetic resonance imaging to rule out underlying pathology, and that any such pathology be treated independently of the venous malformation.

✓ An unusual case of an iatrogenic dural arteriovenous fistula is reported. The patient presented with a history of progressive generalized headache over a period of 3 to 4 weeks. Computerized tomography demonstrated a chronic subdural hematoma that was successfully evacuated by burr-hole drainage. The patient's postoperative course was complicated by recurrent acute subdural hematomas at the drainage site. Coagulation studies were unremarkable. Selective external carotid angiography demonstrated a small dural arteriovenous fistula adjacent to the burr hole used for the initial operative procedure. Extension of the bone flap and coagulation of the fistula resulted in a good outcome. In the patient with recurrent acute subdural hematoma, the possibility of a vascular malformation must be considered. Selective internal and external carotid angiography is key to the correct diagnosis.

✓ The case is reported of a 2-year-old boy born with Marshall-Smith syndrome who had difficulty in swallowing and who exhibited spasticity and quadriparesis due to compression of the medulla and cervical spine. This is the first child with this rare condition reported to have brain-stem compression from bone abnormalities at the craniovertebral junction and who has required surgery.

✓ Fourteen patients with superior cervical spinal cord injuries and the clinical signs and symptoms of cruciate paralysis are presented. This rare injury pattern is characterized by weakness of the upper extremities with little or no compromise of lower-extremity function following trauma to the superior spinal cord. Anatomically, cruciate paralysis is thought to represent selective injury to descending corticospinal tracts as they decussate at the cervicomedullary junction. The clinical and radiographic findings of each patient are outlined and the incidence and natural history of the injury syndrome, including a review of the literature, are presented.

To the Editor. —Drs Minkoff and Willoughby 1 made several excellent points in their Commentary, but then they seemed to contradict themselves within the same article. The article is a clear affirmation that the use of zidovudine in pregnancy provides an unquestioned benefit with "no significant morbidity." The prenatal use of zidovudine is severely impaired by current human immunodeficiency virus (HIV) testing policies. Consequently, more than half of HIV-infected children remain unidentified to their parents or physicians at the time of hospital discharge. The authors state that they cannot find a "rational justification" for unblinding the heelstick survey. I believe they contradict themselves by immediately providing at least two excellent reasons for doing so. First, Pneumocystis carinii pneumonia (PCP) prophylaxis could be initiated earlier in the newborn. Pneumocystis carinii pneumonia is the most common opportunistic infection in pediatric patients with acquired immunodeficiency syndrome (AIDS). Simonds et al 2 recently reported

Tritiated and iodinated arginine vasopressin (AVP) were administered intravenously to human beings and to dogs. The level of plasma radioactivity was measured with time and showed a single exponential function in all cases, except with I113 vasopressin in human beings, where two exponential components were evident. In the dog, the half-time for the disappearance of radioactivity from plasma ranged from 3.5 to 7 min after administration of I113 AVP and from 4 to 5 min after H3 AVP. In similar experiments in man, I113 AVP gave a fast component with a half-time ranging from 0.3 to 2 min and a slow component with a half-time ranging from 1.6 to 6.5 min, whereas H3 AVP gave a single component with a half-time ranging from 2.3 to 5.5 min. The similarity in the disappearance curve of antidiuretic activity and the disappearance curve of radioactivity suggests that the latter reflects the rate of degradation of the biologically active hormone. Therefore, these labeled hormones appear to be useful tools for evaluation of vasopressin turnover in physiological and clinical conditions alleged to be associated with increased levels of circulating antidiuretic hormone or with abnormal rates of vasopressin production, release, or inactivation. Submitted on March 9, 1961

To the Editor:— In 1956, Maurer 1 reported the successful removal of a lymphangioma of the thoracic duct which, as far as we have determined, is the only previous report of this tumor. Our purpose is to report another surgically proven lymphangioma of the thoracic duct presenting, as did Maurer's case, with spontaneous right chylothorax. A brief summary of the pertinent details follows: A 47-year-old obese woman, well, except for hypertension for many years, developed the gradual onset of shortness of breath in mid December, 1961. She was found to have a sterile chylous pleural effusion on the right. No malignant cells could be found. After thoracentesis she remained asymptomatic for 3 weeks with no reaccumulation of the fluid. However, a month after the initial onset of symptoms, she had a rapid reaccumulation of chylous effusion and was readmitted to the hospital for further evaluation and treatment. She was found

ConclusionsIt has been shown that a purified growth hormone preparation of the anterior pituitary which is practically free of lactogenic, adrenocorticotropic, thyrotropic, and gonadotropic hormones, produces a marked increase in glucose excretion in the sucrose-fed partially depancreatized rat.