Mitsuhiro Hara

Gamma knife radiosurgery for arteriovenous malformations : Long-term follow-up results focusing on complications occurring more than 5 years after irradiation

The detailed long-term follow-up results of 40 patients treated for cerebral arteriovenous malformations with gamma knife radiosurgery are presented, with special reference to postradiosurgical complications that can develop many years after irradiation. The follow-up period after radiosurgery was 54 to 205 months, excluding one mortality, with a mean and a median of 106 and 97 months, respectively. One patient (2.5%) has, to date, refused all neuroimaging follow-up examinations. Complete nidus obliteration was angiographically confirmed in 26 patients (65%) between 1 and 5 years after radiosurgery. In the remaining 13 patients (32.5%), although significant shrinkage of each nidus was angiographically demonstrated, complete obliteration was not attained during a 3- to 7-year period of follow-up after radiosurgery. Among these 13 patients, 1 underwent surgical extirpation of the nidus and 5 underwent second courses of gamma knife radiosurgery between 3 and 6 years after initial treatment; in 3 of the 5 patients, complete nidus obliteration was angiographically confirmed between 1 and 3 years after the second course of radiosurgery. There were no radiation- or arteriovenous malformation-related mortalities. However, we did experience one angiography-related mortality. We also experienced one morbidity (probably caused by hemorrhagic stroke), which developed 5 years after 2-year postradiosurgical angiography had demonstrated complete obliteration, and three radiation-related morbidities, two of which (hemiparkinsonian syndrome and visual field disturbances caused by delayed cyst formation) occurred 5.5 and 7 years, respectively, after irradiation. Furthermore, we observed another two patients who, although asymptomatic to date, showed delayed cyst formation on magnetic resonance imaging 5 and 10 years after irradiation, respectively. In total, 3 (23%) of 13 patients who underwent computed tomography and/or magnetic resonance imaging more than 5 years after radiosurgery showed delayed cyst formation. In conclusion, long-term follow-up, particularly with the use of neuroimaging techniques, is necessary even after the treatment goal has been achieved.

Alternatively spliced forms of cyclin D1 modulate entry into the cell cycle in an inverse manner.

Alternative splicing of cyclin D1 gene mRNA has recently been demonstrated. The novel transcript shows no splicing at the downstream exon 4 boundary and encodes a protein with an altered carboxyl-terminal domain that is a cyclin D1 variant; exon 5 is not included in the coding sequence which terminates downstream of exon 4. We here produced cells that exogenously express each form of cyclin D1 and analysed their cell cycle regulation. We found that (1) alternative splicing forms of cyclin D1 modulated entry into the cell cycle in an inverse manner; (2) both splicing forms suppressed cell growth; and (3) cells overexpressing form [a] were inhibited from entry into and completion of the S phase, although form [b]-expressing cells showed no reduction of G1- to S transition. We also found that overexpression of either cyclin D1 form up-regulated Rb gene products, suggesting that this up-regulation may be one of the causes of growth suppression in cyclin D1 overexpressing cells.

Aneurysms associated with moyamoya disease.

Seven cases of moyamoya disease accompanied by an aneurysm were studied. The patients, two males and five females, were 13 to 57 years old (average, 32). The cases were classified into two groups: Group A (five cases), in which the aneurysm was located within the moyamoya vessels, and Group B (two cases), in which the aneurysm was located within the circle of Willis and remote from the moyamoya vessels. In all Group A cases, the presenting episode was intracerebral and intraventricular hemorrhage due to rupture of the aneurysm. One patient suffered two separate attacks. In this case, the aneurysm disappeared spontaneously. In one of the two Group B cases, there was hemorrhage from an anterior communicating artery aneurysm. In the other case, with a basilar-superior cerebellar artery aneurysm, there was hemorrhage from the moyamoya vessels.

Expression of p53, MDM2 protein and Ki-67 antigen in recurrent meningiomas.

Association of p53 gene abnormalities with tumor progression and prognosis of many neoplasms has been demonstrated, but little is known about the clinical significance of p53 abnormalities in meningiomas. The significance of p53 protein expression in recurrent meningiomas and its relationships with MDM2 protein and proliferation activity were investigated by analyzing 39 meningiomas immunohistochemically. p53 protein was expressed in 11 (35%) of 31 non-recurrent and 7 (88%) of 8 recurrent meningiomas. A high frequency of p53 expression was observed in recurrent meningiomas, which tended to have a high p53 positive index (p53 PI), indicating that p53 immunoreactivity may be a marker for predicting tumor recurrence. Four recurrent meningiomas with high p53 PIs were analyzed by the polymerase chain reaction-single strand conformation polymorphism method to detect p53 gene mutations, but none were found in exons 4–8 of this gene. Fifteen (71%) of 21 MDM2-positive and 3 (17%) of 18 MDM2-negative tumors expressed p53 protein, showing that MDM2 expression was more common in meningiomas with p53 expression. p53 immunoreactivity in the absence of mutation may indicate stabilization of the wild type through interaction with the MDM2 protein. The Ki-67/MIB-1 proliferation index (MIB-1 PI) correlated well with recurrence. The p53-positive tumors had a significantly higher mean MIB-1 PI than p53-negative tumors, suggesting that wild-type p53 inactivation by the MDM2 protein may be involved in controlling the proliferative activity in meningiomas. In conclusion, immunohistochemical examination for p53 protein as well as proliferative activity may help predict the malignant potential of tumor recurrence.

Transcranial Doppler monitoring in severe brain damage: relationships between intracranial haemodynamics, brain dysfunction and outcome.

Transcranial Doppler (TCD) monitoring in the middle cerebral (MCA) and common carotid arteries (CCA) was studied in 105 comatose patients with severe brain damage. TCD-measured velocity waveforms in the MCA were evaluated in relation to loss of cerebral function as assessed by EEG and compressed spectral arrays, loss of brain stem function as measured by somatosensory and auditory evoked potentials, loss of all brain function and the clinical outcome. The velocity waveforms exhibited six patterns: continuous forward flow (FF); diastolic no flow (NF); diastolic reverse flow with (RF) or without (DRF) diastolic FF; brief systolic FF (SFF); and undetectable (U). In the 58 fatal cases, the appearance of RF/DRF or SFF in the MCA more often preceded loss of brain stem function than loss of cerebral function. A U pattern in the MCA, which was confirmed by loss of FF in the CCA, was correlated with loss of brain stem function. Only one of the 47 survivors showed DRF in the MCA. No patients in whom SFF or U was observed in the MCA survived. Therefore the presence of these patterns is reliably predictive of brain death. Intracranial diastolic reverse flow (DRF), however, indicates imminent loss of brain function and the need for prompt resuscitative measures.

Comparative Effects of Hypothermia, Barbiturate, and Osmotherapy for Cerebral Oxygen Metabolism, Intracranial Pressure, and Cerebral Perfusion Pressure in Patients with Severe Head Injury

UNLABELLED In order to select the optimal neurointensive treatment for patients with severe head injury and intracranial hypertension, the effects of hypothermia (HT), barbiturates (BT), and osmotic agents (OT) on focal and diffuse cerebral oxygen metabolism were evaluated by means of continuous monitoring of bifrontal regional oxygen saturation (rSO2), jugular bulb oxygen saturation (SjO2), jugular bulb temperature (Tjb), intracranial pressure (ICP), and cerebral perfusion pressure (CPP). PATIENTS AND METHODS Cerebral oxygen metabolism in SjO2 and rSO2, ICP, CPP, and Tjb were continuously monitored in severe head injury patients with Glasgow Coma Scale < 8, ages 10-62: 13 with focal and 10 with diffuse injuries. The effects of BT (n = 6), HT (n = 9), and OT (n = 8) on these parameters (ICP/CPP, SjO2, and rSO2) were compared. Evaluations were performed in terms of: a) Percentage of abnormal values based on normal control values; ICP < 20 mm Hg, CPP > 60 mm Hg, SjO2 55-75%, and rSO2 60-80% were calculated, b) Effects of pentobarbital dose (mg/kg/h) for the parameters compared among < 1.0, 1.1-2.0, 2.1-3.0, and > 3.1. c) Effects of Tjb (degree C) on parameters compared among hyperthermia (> 38 degrees C), normothermia (36-37.9 degrees C), mild hypothermia (34-35.9 degrees C) and moderate hypothermia (< 33.9 degrees C). RESULTS a) Abnormal data differed significantly among the three treatment groups. rSO2 showing ischemia on the affected side was more marked in BT than in HT or OT. b) ICP decreases and CPP increases correlated significantly with the pentobarbital dose. c) ICP decreases and CPP increases correlated significantly with decreased Tjb. CONCLUSION The therapeutic effects of hypothermia, barbiturates, and osmotherapy on cerebral oxygen metabolism and ICP/CPP are different according to the underlying pathological lesions of patients with severe head injury.

Cine magnetic resonance imaging of aqueductal stenosis

Cerebral aqueductal stenosis is one of the most common causes of congenital and acquired hydrocephalus, but the etiology, pathophysiology and cerebrospinal fluid (CSF) dynamics of aqueductal stenosis have yet to be clarified. Utilizing cardiac gated cine magnetic resonance (MR) imaging, we evaluated aqueductal configuration and pulsatile motion of brain and CSF flow stimulated by cardiac pulsation in five patients with nontumoral aqueductal stenosis. Cine MR of four cases revealed obliteration of the aqueduct by thickening mesencephalic tectum, turbulent CSF flow in the III ventricle, and absence of flow-related signal void, which in all normal cases indicates CSF movement within the aqueduct. In the remaining fifth case, with proximal dilation of the aqueduct resulting from thinning of the tectum, distortion of caudal (distal) tectum related to pulsatile motion of the brain caused funnel-like narrowing of the aqueduct, leading to incomplete obstruction and the absence of upward CSF flow during diastole.

Congenital fistula of the dural carotid-cavernous sinus: case report and review of the literature.

The case of a 2-month-old boy with a congenital fistula of the dural carotid-cavernous sinus is presented. This is a rare vascular anomaly in infancy, and it may cause acute changes in vision. The child was initially followed up for 1 year to see if spontaneous thrombosis would occur. The symptoms persisted, however, and intravascular surgery using platinum coils was performed for closure. After treatment, the symptoms completely resolved. Literature pertaining to this anomaly has been reviewed with particular emphasis on dural fistulas of the cavernous, transverse, sigmoid, and straight sinuses in infancy.

A temporal study of survival of patients with pontine gliomas.

SummaryTwenty-four cases of pontine glioma were treated over a 16 year period. Survival times are discussed, particularly long survival times, on the basis of 13 cases autopsied. Onset occurred in an age range of 5 to 60 years, and 5 of the 13 autopsied cases involved children. The average survival time was 9 months except for 2 long survival cases, one of 4 years and 7 months and the other of 14 years and 10 months.The longer the survival time, the greater was the number of neurological symptoms detected, but there was no relationship between the involvement of cranial nerves and the survival time. The improvement of cranial nerve disorders was more prominent in the long survival cases than that of other neurological disturbances.The time from onset of symptoms to admission was longer for long survival cases than the others, and the autopsies of two long survival cases revealed astrocytoma. There were no cases which survived more than one year in the glioblastoma multiforme group.Zusammenfassung24 Fälle von Gliomen der Pons wurden am Toranomon Hospital und der Kyorin Universität über 16 Jahre lang behandelt. Die Länge der Überlebenszeit wird diskutiert, besonders in den Fällen eines langen Überlebens, wobei als Basis der Diskussion 13 Fälle mit Autopsie herangezogen werden. Beginn der Erkrankung meistens zwischen 5 und 60 Jahren; 5 der 13 Patienten, bei denen eine Autopsie durchgeführt wurde, waren Kinder. Die durchschnittliche Überlebenszeit war 9 Monate außer bei zwei besonders lange überlebenden Patienten, von denen einer 4 Jahre und 7 Monate, der andere 14 Jahre und 10 Monate überlebte.Je länger die Überlebenszeit, desto größer war die Zahl der neurologischen Symptome, aber es gab keinen echten Zusammenhang zwischen dem Befall der Hirnnerven und der Überlebenszeit. Im Gegenteil war bei den lange Zeit überlebenden Fällen die Besserung in den Hirnnervenausfällen deutlicher als in den übrigen neurologischen Symptomen. Die Zeit zwischen Auftreten des ersten Symptoms und der Einlieferung ins Hospital war bei den Patienten mit langem Überleben größer als in den übrigen Fällen; in zwei Fällen mit langem Überleben und Autopsie war der Tumor ein Astrocytom. Bei der Gruppe mit multiformen Glioblastomen dagegen gab es keinen Patienten mit einer Überlebenszeit von länger als einem Jahr.

CSF shunt physics: factors influencing inshunt CSF flow

Cerebrospinal fluid (CSF) in a shunt does not have a constant flow rate. The flow fluctuates from 0.01 ml/min to 1.93 ml/min according to each patients own daily supine rhythmic pattern. We determined and evaluated the factors influencing CSF flow in a shunt in 19 cases of hydrocephalus. Postural changes, such as head elevation, led to increases by over 0.04 ml/min in inshunt CSF flow, while inshunt CSF flow in the supine position was less than 0.04 ml/min. Respiratory changes, such as coughing and apnea-hyperventilation, also influenced inshunt CSF flow. Changes in intracranial pressure (ICP) corresponded to changes in inshunt CSF flow. Inshunt CSF flows were higher than average during the night, the flows being stimulated by increases in ICP especially during REM sleep.