α-secretase cleaved amyloid precursor protein (APP) accumulates in cholinergic dystrophic neurites in normal, aged hippocampus.

AIMS: Dystrophic neurites are associated with ß-amyloid (Aß) plaques in the brains of Alzheimer's disease (AD) patients and are also found in some specific areas of normal, aged brains. This study assessed the molecular characteristics of dystrophic neurites in normal ageing and its difference from AD. METHODS: We compared the dystrophic neurites in normal aged human brains (age 20-70 years) and AD brains (Braak stage 4-6) by immunostaining against ChAT, synaptophysin, γ-tubulin, cathepsin-D, Aß1-16, Aß17-24, amyloid precursor protein (APP)-CT695 and APP-NT. We then tested the reproducibility in C57BL/6 mice neurone cultures. RESULTS: In normal, aged mice and humans, we found an increase in clustered dystrophic neurites of cholinergic neurones in CA1 regions of the hippocampus and layer II and III regions of the entorhinal cortex, which are the major and earliest affected areas in AD. These dystrophic neurites showed accumulation of sAPPα peptides cleaved from the amyloid precursor protein by α-secretase rather than Aß or C-terminal fragments. In contrast, Aß and APP-CTFs accumulated in the dystrophic neurites in and around Aß plaques of AD patients. Several experiments suggested that the accumulation of sAPPα resulted from ageing-related proteasomal dysfunction. CONCLUSIONS: Ageing-associated impairment of the proteasomal system and accumulation of sAPPα at cholinergic neurites in specific areas of brain regions associated with memory could be associated with the normal decline of memory in aged individuals. In addition, these age-related changes might be the most vulnerable targets of pathological insults that result in pathological accumulation of Aß and/or APP-CTFs and lead to neurodegenerative conditions such as AD.

Elimination of porcine reproductive and respiratory syndrome virus from a seedstock breeding farm and a supplying boar stud by a modified test and removal method.

To eliminate porcine reproductive and respiratory syndrome virus (PRRSV) from a supplying boar stud, samples of serum and semen from 118 boars were assessed three times a month by an indirect fluorescent antibody (IFA) test to detect antibodies, and by a nested reverse transcriptase-PCR (nRT-PCR) to detect the genome of PRRSV. The boars detected as persistently infected carriers were culled. A PRRSV-negative population of boars was established after three months and no semen positive for the virus was detected for six months. Subsequently, a three-step plan was introduced to eliminate PRRSV from the seedstock breeding farm during three parity cycles on the farm over 15 months, each step taking five months. In step 1, umbilical cords taken from piglets at birth and serum samples taken from their dams at the start of weaning were subjected to ifa and nRT-pcr analysis. The sows with PRRSV detected in serum by nRT-pcr were regarded as carrier sows and culled. The rates of detection of PRRSV were reduced from 5 percent to 2.5 percent in the sera of the sows, and from 14.8 percent to 1.8 percent in the umbilical cords of the piglets. In step 2, the sows that had farrowed the piglets with PRRSV detected by nRT-PCR in their cords were considered to have transmitted the infection and removed. During step 2, the virus detection rates in umbilical cords by nRT-pcr were reduced, but not completely eliminated. In step 3, 10-week-old nursery pigs with antibodies to PRRSV in their serum by ifa and elisa were culled. The three steps established the PRRSV-negative state of the multisite farm containing the breeding and nursery farm, and the PRRSV-negative state of both the multisite farm and the supplying boar stud was evaluated by monthly monitoring over at least one parity cycle of the farm for five months.

Ictal electrocorticographic findings related with surgical outcomes in nonlesional neocortical epilepsy.

PURPOSE: To characterize ictal electrocorticographic features related to surgical outcomes in nonlesional neocortical epilepsy (NE). METHODS: We analyzed 187 ictal electrocorticograms (ECoG) obtained from 18 patients who had undergone presurgical evaluation and subsequent neocortical resections (frontal: seven, parietal: one, occipital: four, multilobar: six). None of them had any MRI-detectable lesions. Various ECoG data sets recorded from eight patients who achieved a favorable surgical outcome (either seizure free or more than 90% reduction of seizure frequencies) were compared with that from ten patients with unfavorable outcome (less than 90% reduction of seizure frequencies) (follow up duration: 47+/-11 months). RESULTS: Reproducible ictal onset zone (IOZ) in recurrent seizures (P=0.013) and persistent ictal discharges in IOZ from the onset to the end of seizure (P=0.004) were found more frequently in the patients with good outcome. Ictal onset patterns consisting of low voltage fast or high amplitude beta spikes predicted a good surgical outcome while rhythmic sinusoidal activity or rhythmic spike/sharp waves of slow frequency were predictive of poor outcome (P=0.01). The ictal onset rhythm consisting of gamma or beta frequencies was more prevalent in the favorable group (P=0.015). CONCLUSIONS: The presence of stable ictal circuit suggested by the consistent earliest activation of specific electrodes in the repetitive seizures (reproducible IOZ) and the active participation of IOZ throughout the attack were valuable prognostic factors in addition to the morphology and frequency of ictal onset rhythm.

Neural phenotype expression of cultured human cord blood cells in vitro.

Neural stem cells have been proposed as useful vectors for treating diseases in the CNS, but their utility is severely limited by lack of accessibility. Brain development is ongoing extensively in early postnatal life. However, it is unclear whether stem cells that differentiate into neurons exist in the blood during early postnatal life. We showed in this experiment that neural markers (NeuN, neurofilament, MAP2, GFAP) are expressed and long cytoplasmic processes are elaborated in the cultured human cord blood monocytes prepared from newborn umbilical blood. These results suggest that stem cells in human cord blood may be potential sources of neurons in early postnatal life. We suggest that the neonatal blood system functions as a circulating pool of different types of stem cell.

Transcolumellar approach in transsphenoidal pituitary surgery for patients with small nostril.

OBJECTIVE: Sublabial approach has been widely used as the standard technique for transsphenoidal pituitary surgery. But it has several possible drawbacks, such as; postoperative flat nose deformity, hypesthesia of upper gum, and feeding difficulty until 2 to 3 weeks after surgery. As an alternative, an endonasal approach was adopted for patients who had large nostrils, such as white or acromegalic patients. In patients with small nostrils, especially oriental people, it requires an additional tension release incision that leaves a definitely visible scar at the base of nose. STUDY DESIGN: We applied the transcolumellar approach, which modified the external rhinoplasty approach on the 136 cases of transsphenoidal pituitary surgery that were performed from 1994 to June 1999. RESULTS: In all patients, we found we could reach the anterior portion of nasal septum in 7 to 8 mm in depth from the skin surface and eliminate the disadvantages of sublabial and endonasal approach. Also, this method can markedly reduce the surgical dissection time and blood loss. CONCLUSIONS: We concluded that this technique was relatively simple and more than adequate in most transsphenoidal pituitary surgery, even in patients with small nostrils.

Selective posterior rhizotomy in children with cerebral palsy: a 10-year experience.

We reviewed our 10-year experience of selective posterior rhizotomy (SPR), with an emphasis on surgical outcome concentrated on improvements in functional ability and adverse effects. We had performed SPR in 208 patients between 1990 and 1999. All patients showed an overall improvement (over 95%) in spasticity, passive range of motion, and gait pattern. Preoperative ambulatory functional level and age were very important predictive factors for further improvements in postoperative functional ability. Compared with the younger children, the older ones lacked a full range of motion preoperatively, and they continued to lack a full range of motion postoperatively, despite the decrease in tone achieved by SPR. Most postoperative complications such as hypotonia, urinary retention, spinal deformities, and sensory changes were temporary and not functionally important. We conclude that SPR is an effective method of alleviating spasticity and provides lasting functional benefits at acceptable complication levels in spastic children with cerebral palsy.

A co-operative study: clinical characteristics of 334 Korean patients with moyamoya disease treated at neurosurgical institutes (1976-1994). The Korean Society for Cerebrovascular Disease.

A co-operative study was conducted to determine the clinical characteristics of patients with moyamoya disease who were diagnosed and treated at neurosurgical institutes in Korea before 1995. Twenty-six hospitals contributed 505 cases and among them, the clinical characteristics of 334 patients with definite moyamoya disease were evaluated. The number of patients began to increase from the late 1980s, and after that approximately 20 patients were treated each year. There were two age peaks: from six to 15 and from 31 to 40 years of age. Haemorrhagic manifestations occurred in approximately 43% of the patients. The major clinical manifestations were haemorrhage in adults (62.4%) and ischaemia in children (61.2%). Overall 54.5% of the patients experienced decreased consciousness levels, mainly due to intracranial haemorrhage or cerebral infarction. In the patients with ischemic manifestations, the adult patients were more likely to have cerebral infarction than the pediatric patients (80% vs. 39%) and the pediatric patients were more likely to have TIA (61% vs. 25%). Thirty eight percent of the patients underwent bypass surgery and 53% of these procedures were performed bilaterally. Treatment policies, including indications for bypass surgery and commonly used drugs, were somewhat different according to the institution. Overall favorable outcome was 73%, and the most significant factor affecting poor outcome was haemorrhagic manifestation. This article describes the characteristics of 334 patients with moyamoya disease, who were diagnosed and treated at neurosurgical institutes in Korea before 1995.

Quantitative assessment of cerebrospinal fluid hydrodynamics using a phase-contrast cine MR image in hydrocephalus.

This investigation was undertaken to characterize CSF flow at the level of the aqueduct of Sylvius with a phase-contrast cine MR pulse sequence in 28 healthy volunteers. Sixteen patients with obstructive hydrocephalus and 11 patients with normal pressure hydrocephalus (NPH) were investigated with the same sequence before and after CSF diversion. The peak CSF flow velocity and stroke volume in the aqueduct increased significantly in the NPH group and decreased significantly in the obstructive hydrocephalus group. After lumboperitoneal shunting in the NPH group, the retrograde flow of CSF was anterogradely converted and the peak flow velocities decreased somewhat. The clinical diagnosis of NPH was well correlated with the results of cine MRI. After endoscopic III ventriculostomy in the obstructive hydrocephalus group we noted increased CSF flow velocity with markedly increased stroke volume at the prepontine cistern. Phase-contrast cine MR is useful in evaluating CSF dynamics in patients with hyperdynamic aqueductal CSF or aqueductal obstruction.

Endoscopic approach to arachnoid cyst.

A prospective study of 36 consecutive patients with congenital arachnoid cysts treated endoscopically is reported. There were 15 female and 21 male patients. The mean age at the time of diagnosis was 12.3 years (10 days to 38 years). Arachnoid cysts were located in the suprasellar region in 16 patients, the sylvian fissure in 11, the quadrigeminal cistern in 4 and the posterior fossa in 5. Endoscopic fenestration was combined with cysto-peritoneal shunting for 6 temporal cysts and with ventriculo-peritoneal shunting in 1 suprasellar cyst. Mean postoperative follow-up was 4.2 years (range 1-8 years). Follow-up imaging studies showed that 28 arachnoid cysts (77.8%) were obliterated after endoscopic procedures. Long-term clinical results were good in all patients, although the cysts of 8 patients were not reduced in size. There was no mortality or morbidity. We conclude that endoscopic procedures may be a promising alternative to microsurgical operations or shunting for the treatment of arachnoid cysts.

A new experimental model of obstructive hydrocephalus in the rat: the micro-balloon technique.

We used three types of specialized micro-balloons 0.7-1.35 mm in outer diameter instead of kaolin to develop a reproducible rat model of hydrocephalus with a low experimental mortality. The micro-balloon was inserted 6 mm deep into the cisterna magna via a burr hole immediately behind the lambda. The angle of introduction was 50 degrees. We also set up kaolin-induced hydrocephalic models in 25 rats as controls. The kaolin model revealed 52% mortality with an 80% induction rate of hydrocephalus, while the balloon model showed 9% mortality with a 60% induction rate. Balloon-induced hydrocephalus was maximal at 1 week and tended to decrease after 2-3 weeks. The pathological findings were not different between the two models. We concluded that the micro-balloon model for hydrocephalus is an easily reproducible model with low experimental mortality.

Endoscopic surgery for obstructive hydrocephalus.

Endoscopic surgery is popular in the neurosurgical field. The purpose of this study was to determine the role of endoscopy in obstructive hydrocephalus. From 1989 to 1999, we performed 81 endoscopic third ventriculostomies and 10 septostomies. Seventy-one of 81 operations were performed with endoscopic third ventriculostomy alone and 10 patients had endoscopic third ventriculostomy and ventriculoperitoneal shunt simultaneously. Age distribution varied from 2 months to 62 years of age. Our selection criteria included aqueductal stenosis (39 patients) and obstructive hydrocephalus due to tumor or cyst (42 patients). The most common candidate for endoscopic septostomy was atresia of the foramen of Monro (4 patients). Endoscopic septostomy was also performed to simplify shunting in patient; with multiseptated ventricle due to shunt infection, germinoma, thalamic tumor, craniopharyngioma, cyst and brain abscess. Sixty-five of 71 patients who were treated with endoscopic third ventriculostomy alone showed successful results (91.5%). However, 6 patients had unsatisfactory results and they needed a ventriculoperitoneal shunt. With no mortality, transient surgical complications were observed in 7 patients: 2 transient diabetes insipidus from electrical injury to the pituitary stalk, 1 epidural hematoma from sudden drainage of CSF, 1 delayed intraventricular hemorrhage. 2 obstruction of fenestration site and 1 transient memory disturbance from injury to the fornix. Endoscopic septostomy was useful in simplifying shunting in all cases with complicated hydrocephalus. Endoscopic surgery is straightforward and effective in appropriately selected cases with obstructive by drocephalus.

Treatment of germ cell tumors in the pineal region.

The authors retrospectively analyzed 107 patients with primary intracranial germ cell tumor (GCT), who were treated at the Department of Neurosurgery, Yonsei Medical Center between January 1986 and January 1996. The incidence of GCT was 2.8% in pediatric patients with intracranial tumor. Of the 107 tumors, 60 were located in the pineal region, 30 in the suprasellar region, 16 in basal ganglia or the thalamic region, and 1 in the posterior fossa. The 60 pineal GCT consisted of 39 germinomas (29 pure germinomas, 6 germinomas with STGC, 4 germinomas mixed with teratoma), 5 mature teratomas, and 16 nongerminomatous GCT. Thirty patients underwent surgery: their operations took the form of total resection in 14 cases, subtotal resection in 10, and biopsy in 6. Thirty patients (27 with germinomas, 3 with endodermal sinus tumors) were managed without surgery on the basis of radiological findings and tumor markers. The 5-year survival was 91% for 39 patients with germinomas, 80% for 5 with mature teratomas, and 49% for 16 with nongerminomatous GCT. Univariate analysis of prognostic factors with the Kaplan-Meier survival curve showed that histological tumor type, radiological findings, results of tumor marker studies, and response to trial radiation or chemotherapy were highly correlated with outcome. Chemotherapy was beneficial as the method of trial treatment in pineal GCT and treatment in recurrent tumors. The administration of trial chemotherapy or radiotherapy without tissue biopsy is well justified as a treatment modality in pineal GCT suspected on the basis of radiological findings and tumor marker studies. Aggressive multimodality approaches with surgery, radiotherapy, and chemotherapy are necessary to improve the outcome in these tumors. We propose new protocol for treatment of germ cell tumors in the pineal region, which is based on a minimally invasive approach.

Identical characteristics of the patient populations with pineal region tumors in Japan and in Korea and therapeutic modalities.

The therapeutic modalities used for tumors of the pineal region in Western countries differ from those in Japan, mainly because of the different patient populations. An extensive survey was conducted to delineate the racial differences in Japan and in Korea in the epidemiology and recent therapeutic modalities for this tumor group. Among the members of International Society for Pediatric Neurosurgery (ISPN), 15 from Japan and 5 from Korea reported their recent findings in 118 (1-25 years of age, mean 7.38-year period) and 125 (1-12 years of age, mean 6.69-year period) histologically verified cases, respectively. The patient populations in the two countries were found to be almost identical, with an extremely high incidence of germ cell tumors representing 71.2% (in Japan) and 80.0% (in Korea) of all pineal region tumors and neuroectodermal tumors representing only 15.2% and 16.8%, respectively. The most common type of pineal region tumor was germinoma (46.6% in Japan and 47.2% in Korea). The majority of tumors were radio- and/or chemosensitive, and adjuvant therapy rather than extensive surgery played the major role in the treatment in both countries. Radical resection of the tumor was recommended as the initial procedure by only 22.2% of neurosurgeons in Japan and 16.6% in Korea. Biopsy was recommended by 38.9% and 50.0%, and radiation therapy by 38.9% and 37.5%, respectively. A minimally invasive procedure, by either a neuroendoscopic (33.3% of biopsies in Japan) or a stereotactic approach (33.3% of biopsies in Korea), was considered to be appropriate as the initial procedure. The study disclosed the almost identical epidemiology of this brain tumor in Japan and in Korea and clarified the consequent therapeutic modalities. The authors emphasize that minimally invasive tissue diagnosis with or without tumor debulking should be considered as the initial step for the treatment planning of the pineal region tumor, followed by the most commonly indicated major procedures, including radiation therapy, chemotherapy and/or radical resection with various methodologies.

Pathogenesis of arachnoid cyst: congenital or traumatic?

For clarifying the pathophysiology of arachnoid cysts and reestablishing therapeutic criteria for such cases, we reviewed a series of 90 cases with arachnoid cysts focusing on the traumatic origin. Arachnoid cysts of congenital origin have been well known. But we suspected that 14 out of 90 patients (15.6%) with arachnoid cyst were closely related to head trauma. Seven of them suffered from head traumas in infancy. The episodes of head trauma included falling down in 4 patients, slipping down in 2 patients, and a motor vehicle accident in 1 patient. Traumatic arachnoid cysts had a latent period from head trauma to initial clinical manifestation. The mean latent period was 2.2 years, ranging from 10 months to 6.2 years. Six of 7 arachnoid cysts were located in the suprasellar area and 1 at the posterior fossa. An other 7 patients had a history of perinatal trauma. We postulate that head trauma in infancy may contribute to the pathogenesis of arachnoid cyst in some cases.

Natural history of moyamoya disease: comparison of activity of daily living in surgery and non surgery groups.

The present study was undertaken to reach a clearer understanding of the natural history of Moyamoya disease. Follow-up studies were performed in 88 patients with Moyamoya disease. They were divided into the ischemia group and the hemorrhage group. The activity of daily living (ADL) of each groups were followed up and compared between those who were surgically treated and conservatively managed. Ischemic manifestations were more common in the younger children and tended to be recurrent, whereas hemorrhagic manifestations were more common in the adults. Follow-up duration of the 36 patients, who were surgically treated, ranged from 6 to 86.4 months (mean: 28.8 months). During the follow-up period, ADL was improved in 17 of 31 ischemic Moyamoya patients (55%); the condition was unchanged in nine (29%); and aggravated in five (16%). Follow-up duration of the 52 patients who were managed without surgery ranged from 12 to 216 months (mean: 67.2 months). In 35 patients of the ischemia group, ADL was aggravated in 49% and improved in only 26% during the follow-up period. However, ADL was aggravated in 12% of 17 hemorrhagic patients, but improved in 53%. Our result suggest that indirect revascularization procedures are effective for prevention of recurrent ischemic attacks which is common in pediatric patients. However, the effectiveness of indirect revascularization for hemorrhagic Moyamoya disease is not clear and requires extended follow-up study.

An analysis of the natural history of cavernous malformations.

BACKGROUND: The treatment of cavernous malformations has been controversial. Some reports suggest that surgical resection of the lesion for the prevention of recurrent hemorrhage should not be considered because of low hemorrhagic risk. However, the role of surgery in management of cavernous malformations is undergoing reevaluation. The decision for surgical resection should be based on a careful analysis of the natural history of this lesion, which is not well understood. METHODS: We investigated, retrospectively, the natural history of 108 cavernous malformations in 62 patients. Individual cavernous malformations were divided into four categories on the basis of magnetic resonance (MR) findings. The pattern of clinical and radiologic presentation and outcomes of management were analyzed. RESULTS: The age of the patients ranged from 4-63 years (mean: 32.2 years). Multiple lesions were found in 13 of 62 patients (21%) and two of these patients were siblings. Twenty-five out of 62 patients had suffered recurrent symptoms. The bleeding rate was 2.3%/person/year (1.4%/lesion/year) during 2509.6 patient years. There were no significant differences between the bleeding rates of each type of lesion. During the follow-up period of 12-48 months (mean: 22.4 months), two of 28 patients conservatively treated had recurrent hemorrhages (rebleeding rate: 3.8%/person/year). During the follow-up period of 12-66 months (mean: 21.7 months), recurrent hemorrhages were observed in two of 17 patients with radiosurgery (rebleeding rate: 7.8%/person/year). CONCLUSION: Our study has provided a profile of the natural history of these lesions. Based on our results, we recommend surgical excision of cavernous malformations in those patients with recurrent symptoms or acute progressive symptoms.

Intradural extramedullary xanthoma of the spine: a rare lesion arising from the dura mater of the spine: case report.

OBJECTIVE AND IMPORTANCE: Xanthomatous tumors of the central nervous system are occasionally found in several unrelated diseases such as Hand-Schüller-Christian disease, Weber-Christian disease, histiocytosis X, malignant fibrous histiocytoma, and a complication of metabolic or storage diseases. However, a solitary xanthoma without systemic disease is rare. We present an unusual case of a solitary and benign xanthoma arising in the spinal leptomeninges without systemic diseases or metabolic abnormality, including a lipid profile. CLINICAL PRESENTATION: A 16-month-old male patient was admitted with a complaint of spastic paraparesis. His magnetic resonance images revealed an intradural extramedullary tumor that showed isosignal intensity on T1-weighted images and high signal intensity on T2-weighted images with homogenous gadolinium enhancement. INTERVENTION: The tumor arising from the spinal meninges was totally removed. Histological findings and immunochemical studies positive for CD68 and lysozyme stain showed abundant histiocytic cells with foamy cytoplasm. Negative S-100 protein in the immunohistochemical study and the absence of Birbeck granules on an electromicroscopic study excluded the possibility of Langerhan's histiocytosis. These findings corresponded to xanthoma. The patient had no abnormality of lipid metabolism or familial history of xanthoma. CONCLUSION: The patient improved enough to walk by himself 3 months after the operation.

Huge Langerhans cell histiocytosis granuloma of choroid plexus in a child with Hand-Schüller-Christian disease. Case report.

In the literature, only two previous cases of presumed Langerhans cell histiocytosis (LCH) granuloma involving choroid plexus have been reported in patients with Hand-Schüller-Christian (HSC) disease, but those cases were not verified by immunohistochemistry or electron microscopy. The authors report a case of LCH granuloma of the choroid plexuses of bilateral lateral ventricles and the fourth ventricle in a child affected by HSC disease. This disease was confirmed by the presence of Birbeck granules on electron microscopy and positive reactivity to S-100 protein. Clinical, radiographic, and histological features are discussed. This case illustrates that LCH granuloma should be considered in the differential diagnosis of intraventricular masses.

Brain tumors diagnosed in the first year of life in five Far-Eastern countries. Statistical analysis of 307 cases.

A statistical survey is presented of brain tumors diagnosed in the first year of life (from five Far-Eastern countries) in relation to the racial differences in tumor types, congenital factors, and general clinical features. Of the 307 cases collected, 262 were verified histologically, and astrocytomas comprised 23.3%, medulloblastomas 17.2%, ependymomas 11.1%, choroid plexus papillomas 10.7%, teratomas 8.4%, primitive neuroectodermal tumors 4.2%, meningiomas 2.3%, and others 22.9%. There were statistically significant racial differences in comparison with the worldwide survey done by the International Society for Pediatric Neurosurgery Education Committee (1987) on the same subject. In the Far-Eastern population, medulloblastoma and teratoma were more common (P less than 0.05), whereas astrocytoma was less frequent (P less than 0.01) than reported in the worldwide survey. The malformative factors were suggested in 18 cases in which various associated congenital anomalies were observed. Vascular anomalous lesions, mostly in the extracranial organs, were most common, comprising 61.1% of the associated malformations. Hereditary factors were less commonly demonstrated in these tumors than were anomalies in the major congenital central nervous system. Among the 307 cases, there was one instance (0.3%) of nearly identical tumors occurring in twin brothers. The specific clinical manifestations of brain tumors involving the immature brain were again apparent in this survey, as were the poor survival rates and poor functional prognosis.

Primary malignant lymphomas of the central nervous system: radiotherapy results in 12 cases.

Twelve patients with primary lymphomas of the central nervous system were treated in the Department of Radiation Oncology, Yonsei University College of Medicine, between 1976 and 1987. There were seven males and five females ranging from 19 to 63 years of age. They had single (6 cases) or multiple (6 cases) discrete intracerebral nodules. All patients were treated with radiation therapy. Surgical resection was performed in five cases and intrathecal chemotherapy with methotrexate was performed in seven cases after radiotherapy. All patients except one had received whole brain irradiation with a median dose of 4000 cGy. The radiation dose for a primary tumor was 4800-6000 cGy (median 5560 cGy). Initial response to radiation was excellent with a 91.7% complete response rate, but late recurrences were noted and the median survival was 42.3 months. Intracranial recurrences were observed in two patients who received less than 4000 cGy to the whole brain without intrathecal chemotherapy. Although intracranial recurrence was not seen in the patients receiving intrathecal chemotherapy after radiation, a high incidence of necrotizing leukoencephalopathy was noted. High dose irradiation with a minimum of 4000 cGy to the whole brain and more than 5000 cGy to the primary tumor is recommended for the treatment of primary CNS lymphomas. Combined use of chemotherapy should be carefully attempted because of the increased toxicity.