Overlapping stimulation of subthalamic nucleus and dentato-rubro-thalamic tract in Parkinson's disease after deep brain stimulation.

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) reduces tremor, rigidity, and akinesia. According to the literature, the dentato-rubro-thalamic tract (DRTt) is verified target for DBS in essential tremor; however, its role in the treatment of Parkinson's disease is only vaguely described. The aim of our study was to identify the relationship between symptom alleviation in PD patients and the distance of the DBS electrode electric field (EF) to the DRTt. METHODS: A single-center retrospective analysis of patients (N = 30) with idiopathic Parkinson's disease (PD) who underwent DBS between November 2018 and January 2020 was performed. DRTt and STN were visualized using diffusion-weighted imaging (DWI) and tractography protocol of magnetic resonance (MR). The EF was calculated and compared with STN and course of DRTt. Evaluation of patients before and after surgery was performed with use of UPDRS-III scale. The association between distance from EF to DRTt and clinical outcomes was examined. To confirm the anatomical variation between DRTt and STN observed in tractography, white matter dissection was performed with the Klingler technique on ten human brains. RESULTS: Patients with EF overlapping STN and DRTt benefited from significant motor symptoms improvement. Anatomical findings confirmed the presence of population differences in variability of the DRTt course and were consistent with the DRTt visualized by MR. CONCLUSIONS: DRTt proximity to STN, the main target in PD DBS surgery, confirmed by DWI with tractography protocol of MR combined with proper predefined stimulation parameters may improve efficacy of DBS-STN.

Process of the Functional Reorganization of the Cortical Centers for Movement in GBM Patients: fMRI Study.

PURPOSE: The aim of this study was to verify whether the functional reorganization of motor cortex is associated with the increase in the size of WHO type IV glioma lesion, that is, disease duration and development, and whether surgical treatment has an impact on cerebral plasticity. METHODS: The study included 16 patients with primary tumors of the brain located at the region of central sulcus. The clinical status of patients and tumor volume was determined. Functional magnetic resonance imaging examinations were performed before and 3 months after operation. RESULTS: The activity of all cortical centers, both contralateral and ipsilateral, was observed in a group of small as well as large tumors. The intensity of activation and the number of activated clusters of small tumors were almost always higher as compared with the large tumors. The frequency of the activity of contralateral areas was similar during the first and the second examination. In the case of ipsilateral centers, the frequency of activation during the second examination was lower. Mean values of t-statistics during the first examination were higher than during the second examination. Supplementary motor area (SMAa) was the only center for which the mean values of activation intensity remained similar. CONCLUSIONS: SMAa seems to play the most important role in the processes of motor cortex plasticity in high-grade glioma patients. Surgery seems not having a significant influence on the pattern of functional reorganization of the cortical centers for movement. Identification of the individual patterns of the reorganization of motor centers plays an important role in clinical practice.

Expression and variability of lipid metabolism genes in intracranial aneurysm.

The objective of this study was to investigate the association between mRNA expression and single nucleotide polymorphisms (SNPs) of the ATP-binding cassette transporter (ABCA1) gene, apolipoprotein A1 (APOA1) gene, low-density lipoprotein (LDLR) gene and RNA gene located in the CDKN2B-CDKN2A cluster (CDKN2B-AS1) involved in lipid metabolism and the occurrence of intracranial aneurysm (IA). Fifty three IA patients, and 27 controls (IA-free) were enrolled in this study and were genotyped for seven single nucleotide polymorphisms. Increased expression of the LDLR gene in IA patients was observed. The A/G genotype and the A allele of the c. -113G>A polymorphism of the APOA1 gene were associated with increased occurrence of IA (ORs 12.36 and 14.14, respectively), while the G/G genotype and G allele showed the opposite tendency (ORs 0.06 and 0.07, respectively). We also detected that the A/A-G/A combined genotype of the c. -113G>A - APOA1 and g.46859A>G - LDLR SNPs was associated with a decreased occurrence of IA. Moreover, the A/G-G/G combined genotype of the c.656G>A - ABCA1 and c. -113G>A - APOA1 was associated with a decreased occurrence of IA. The results of our study suggest the association between expression and variability of lipid metabolism genes and occurrence of IA.

Association of loss of heterozygosity with shorter survival in primary glioblastoma patients.

Loss of heterozygosity (LOH) co-deletion 1p/19q, MGMT promoter methylation and/or IDH1 mutation generally signify a better prognosis for patients with glioma. However, the influence of 1p/19q co-deletion and the LOH on other chromosomes in primary glioblastoma on survival is still debatable. The aim of our study was to identify LOH on chromosomes 1p, 19q, 9p, 10q, 13q, and 17p, and evaluate their impact either alone or 1p/19q co-deletion or by groups of LOH on the overall survival of 42 primary glioblastoma patients without an oligodendroglial component. These patients were additionally molecularly characterized for EGFR amplification, IDH1 mutations and TP53 mutations. We assessed their influence on the overall survival of glioblastoma patients. LOH in at least one of the loci on all examined chromosomes was detected in 65% of cases and was significantly associated with shorter overall survival (hazard ratio 3.07; 95% CI: 1.29-7.31, p = 0.006). 1p/19q co-deletion was infrequent (7.14%) and had no impact on overall survival. Our results indicate that in primary glioblastoma a specific LOH group analysis may be important for the prognosis. LOH 1p/19q co-deletion is rare in glioblastoma without an oligodendroglial component and has no impact on patient survival.

Magnetic resonance spectroscopy in intracranial tumours of glial origin.

BACKGROUND AND PURPOSE: To determine in vivo magnetic resonance spectroscopy (MRS) characteristics of intracranial glial tumours and to assess MRS reliability in glioma grading and discrimination between different histopathological types of tumours. MATERIAL AND METHODS: Analysis of spectra of 26 patients with glioblastomas, 6 with fibrillary astrocytomas, 4 with anaplastic astrocytomas, 2 with pilocytic astrocytoma, 3 with oligodendrogliomas, 3 with anaplastic oligodendrogliomas and 17 control spectra taken from healthy hemispheres. RESULTS: All tumours' metabolite ratios, except for Cho/Cr in fibrillary astrocytomas (p = 0.06), were statistically significantly different from the control. The tumours showed decreased Naa and Cr contents and a high Cho signal. The Lac-Lip signal was high in grade III astrocytomas and glioblastomas. Reports that Cho/Cr ratio increases with glioma's grade whereas Naa/Cr decreases were not confirmed. Anaplastic astrocytomas compared to grade II astrocytomas had a statistically significantly greater mI/Cr ratio (p = 0.02). In pilocytic astrocytomas the Naa/Cr value (2.58 ± 0.39) was greater, whilst the Cho/Naa ratio was lower (2.14 ± 0.64) than in the other astrocytomas. The specific feature of oligodendrogliomas was the presence of glutamate/glutamine peak Glx. However, this peak was absent in two out of three anaplastic oligodendrogliomas. Characteristically, the latter tumours had a high Lac-Lip signal. CONCLUSIONS: MRS in vivo cannot be used as a reliable method for glioma grading. The method is useful in discrimination between WHO grade I and WHO grade II astrocytomas as well as oligodendrogliomas from other gliomas.

Differential diagnosis of intracranial meningiomas based on magnetic resonance spectroscopy.

BACKGROUND AND PURPOSE: To determine in vivo magnetic resonance spectroscopy (MRS) characteristics of intracranial meningiomas and to assess MRS reliability in meningioma grading and discrimination from tumours of similar radiological appearance, such as lymphomas, schwannomas and haemangiopericytomas. MATERIAL AND METHODS: Analysis of spectra of 14 patients with meningiomas, 6 with schwannomas, 2 with lymphomas, 2 with haemangiopericytomas and 17 control spectra taken from healthy hemispheres. RESULTS: All the patients with meningiomas had a high Cho signal (long TE). There were very low signals of Naa and Cr in the spectra of 10 patients. A reversed Ala doublet was seen only in 2 cases. Four patients had a negative Lac signal, whereas 3 had high Lac-Lip spectra. Twelve spectra showed high Cho signals (short TE). In one case the Cho signal was extremely low. All spectra displayed a very low Cr signal, but high Glx and Lac-Lip signals. Ala presence was found only in 3 patients. The mean Cho/Cr ratio (PRESS) was 5.97 (1.12 in normal brain, p < 0.05). Lac-Lip was present in all the meningiomas (STEAM). The Ala signal was seen only in 2 spectra with long TE and in 3 sequences of the short TE sequences. There were both ß/γ-Glx and α-Glx/glutathione signals in all 14 meningiomas. CONCLUSIONS: MRS is unable to discriminate low and high grade meningiomas. The method seems to be helpful in discriminating lymphomas (absent Glx signal), schwannomas (mI signal in the short TE sequences) and haemangiopericytomas (presence of mI band) from meningiomas.

Glioma cells showing IDH1 mutation cannot be propagated in standard cell culture conditions.

BACKGROUND: It has recently been reported by several sources that original (i.e., present in vivo) glioma cell phenotypes or genotypes cannot be maintained in vitro. For example, glioblastoma cell lines presenting EGFR amplification cannot be established. METHODS AND RESULTS: IDH1 sequencing and loss of heterozygosity analysis was performed for 15 surgery samples of astrocytoma and early and late passages of cells derived from those and for 11 archival samples. We were not able to culture tumour cells presenting IDH1 mutations originating from currently proceeded 10 tumours; the same results were observed in 7 samples of archival material. CONCLUSION: The IDH1 mutation is expected to be almost mutually exclusive with EGFR amplification, so glioma cells with IDH1 mutations seem to represent a new group of tumour cells, which cannot be readily analysed in vitro because of their elimination. The reasons for this intriguing phenomenon should be investigated since its understanding can help to define a new therapeutic approach based on simulating in vivo conditions, responsible for tumour cells elimination in vitro. Moreover, a new model for culturing glioma cells in vitro should be designed since the current one does not provide conditions corresponding to in vivo growth.

Magnetic resonance imaging of rare intracranial neoplasms--role of the in vivo 1 h spectroscopy in the radiological differential diagnostics.

BACKGROUND: The object of this study was to evaluate the usefulness of magnetic resonance (MR) spectroscopy in differentiating rare intracranial tumours in adult patients. Review of the literature on results of MR spectroscopy in these lesions is also included. MATERIAL AND METHOD: 89 patients with brain tumours were evaluated preoperatively with in vivo 1.5 T MR spectroscopy (according to eTumour study requirements). 8 of them were diagnosed as having very rare neoplasms: haemangiopericytoma (2), lymphoma (2), plexus papilloma (2), chondroma (1) and purkinjoma (1). Spectra of these tumours were compared to spectra of common brain tumours that could resemble these lesions. RESULTS: MR spectroscopy enabled discrimination between meningiomas and haemangiopericytomas, meningiomas and lymphomas, and purkinjomas or chondromas and other brain tumours. The method was unreliable in distinguishing between glioblastomas and lymphomas. CONCLUSION: The small number of patients made statistical analysis impossible. However, at present, it seems that neuroradiological diagnosis should not rely on MR spectroscopy alone.

BCR expression is decreased in meningiomas showing loss of heterozygosity of 22q within a new minimal deletion region.

Neurofibromin 2 (NF2), located on chromosome arm 22q, has been established as a tumor suppressor gene involved in meningioma pathogenesis. In our study, we investigated 149 meningiomas to determine whether there are additional tumor suppressor genes localized on chromosome 22q, apart from NF2, that might be involved in meningioma pathogenesis. The LOH analysis on chromosome 22q identified two regions of deletion: the first one, which is limited to the NF2 gene locus, and the second one, which is outside this location. The new minimal deletion region (MDR) included the following genes: BCR (breakpoint cluster region), RAB36 (a member of RAS oncogene family), GNAZ [guanine nucleotide binding protein (G protein), alpha-z polypeptide], and RTDR1 (rhabdoid tumor deletion region gene 1). The expression levels of all these genes, including NF2, were subsequently analyzed by quantitative real-time polymerase chain reaction. We observed a significantly lowered expression level of NF2 in meningiomas with 22q loss of heterozygosity (LOH) within NF2 region compared to the one in meningiomas with 22q retention of heterozygosity (ROH, P<0.05). Similarly, BCR showed a significantly lowered expression in meningiomas with 22q LOH within the new MDR compared to cases with 22q ROH (P<0.05). Our data, together with the already published information considering BCR function suggest that BCR can be considered as a candidate tumor suppressor gene localized on chromosome 22q which may be involved in meningioma pathogenesis.

Molecular analysis of chromosome 1, 10 and 19 abnormalities in human oligodendroglial tumors: relationship between frequency of LOH grade, age and gender.

BACKGROUND: Loss of heterozygosity (LOH) on 1p and 19q is observed in most oligodendroglial tumors. LOH on 10q appears to be less common in these tumors as compared to other gliomas. PATIENTS AND METHODS: We reviewed 14 patients with oligodendroglial tumors (10 low-grade and 4 anaplastic oligodendroglioma) to evaluate the frequency of LOH on 1p, 10q and 19q and correlate it with tumor grade and patients' age and gender; 5 loci on 1p and 5 on 19q as well as 4 on 10q were analyzed for LOH using PCR techniques. RESULTS: LOH on 1p together with 19q was detected in 6 tumors, 1 tumor showed deletion of 19q accompanied with deletion on 10q. Deletion on 1p was associated with deletion of 19q (p < 0.005) and mutual associations among deletions at loci on 19q (p < 0.05) were found. Patients with LOH on 1p were younger on average than patients with retained heterozygosity (p = 0.05). Grade II oligodendrogliomas predominated among younger patients (p < 0.01) while grade III oligodendrogliomas predominated among women (p < 0.005). No association between LOH on 1p nor 19q and tumor grade or patients' gender was found. CONCLUSION: Our study provides several clinically interesting findings and further supports the hypothesis of chromosome 1p and 19q involvement in the oligodendroglial cancerogenesis.

GADD45A and EPB41 as tumor suppressor genes in meningioma pathogenesis.

Deletions of 1p occur in approximately 30% of meningiomas. Based on loss of heterozygosity (LOH) analysis, two regions on 1p have been suspected to be carriers of tumor suppressor genes. We chose the GADD45A and EPB41 genes as tumor suppressor candidates based on their function and chromosomal localization. We analyzed 19 cases of meningioma with LOH of 1p by means of sequencing of the GADD45A gene and Western blotting of the GADD45a protein. Twenty cases of meningioma without 1p LOH were also analyzed by Western blotting to find out if changes of the GADD45a protein expression occurred. Nineteen samples with 1p LOH (12 grade I; 7 grade II, WHO classification) and 20 samples without 1p LOH (18 grade I; 2 grade II) were also analyzed by means of real-time polymerase chain reaction to find abnormalities in EPB41 mRNA levels in meningioma. LOH analysis was performed using seven microsatellite markers: D1S508 (1p36.2), D1S199 (1p36.1) D1S2734 (1p36.1), D1S2720 (1p34), D1S197 (1p32), D1S162 (1p32), D1S429 (1p11). LOH analysis confirmed previously described localization of putative tumor suppressor genes on 1p and involvement in meningioma pathogenesis (1p36 and 1p32). The open reading frame of GADD45A and intron splicing sites showed neither mutations nor polymorphisms. GADD45a protein molecular weight and expression level were unaltered in meningiomas with and without 1p LOH. We conclude that the GADD45A gene is not involved in meningioma tumorigenesis. EPB41 gene expression was unchanged in all analyzed meningiomas. This suggests that involvement of the EPB41 gene (4.1R protein) in meningioma pathogenesis should be reconsidered.

Molecular heterogeneity of meningioma with INI1 mutation.

BACKGROUND: INI1 (hSNF5) mutations are linked to rhabdoid tumours, but mutations in meningiomas with hot spot mutations in position 377 have also been reported. AIMS: To analyse the INI1 gene in meningioma. METHODS: Exons 1, 4, 5, and 9 of the INI1 gene were analysed by the polymerase chain reaction and direct sequencing in 80 meningiomas. For all cases, western blotting of the INI1 protein was performed. RESULTS: Only one of the 80 samples showed a cytosine insertion in codon 376. This mutation changed the open reading frame in almost the whole exon 9 and resulted in a longer hSNF5 protein. Complex analysis of the above described tumour sample by western blotting, DNA sequencing, and loss of heterozygosity (LOH) analysis showed that this particular meningioma consisted of heterogeneic cellular components. One of these components had a mutated INI1 gene, whereas in the other component INI1 was intact. CONCLUSIONS: INI1 mutation is a rare event in the molecular pathology of meningiomas. It is possible for the INI1 gene to be mutated in only a proportion of meningioma cells.

Recombinant human thyroid peroxidase produced in insect cells has similar properties to native human thyroid peroxidase.

Purified native human thyroid peroxidase (nTPO) isolated from thyroid tissue and recombinant (r)TPO produced in High Five insect cells have been compared. nTPO and rTPO were purified to about 95% homogeneity and showed similar UV and visual spectra and similar 412 nm per 280 nm absorbance ratios (0.4 for nTPO and 0.4 for rTPO). The nTPO and rTPO guaiacol oxidation enzyme activities were about 1,000 guaiacol units per milligram of protein. TPO autoantibody binding characteristics of nTPO and rTPO were analyzed in an assay based on 125I-labeled nTPO and precipitation with protein A. In the assay, the effect of unlabeled nTPO or rTPO on TPO autoantibody binding from 25 patients sera was studied. Unlabeled nTPO or rTPO (from 0 to 160 ng/mL) inhibited the binding of TPO autoantibodies in a dose-dependent manner in the case of each serum studied (from 100% in the absence of unlabeled TPO to 5%-10% in the presence of 160 ng/mL of TPO). The inhibition profile for each serum was essentially identical in the case of both TPO preparations. The effect of TPO autoantibodies on enzyme activity of rTPO was analyzed after incubation of rTPO with TPO autoantibody-positive serum immunoglobulin G (IgG) (n = 12), TPO monoclonal antibodies reactive with two different epitopes on the TPO, IgG (n = 3) from glutamic acid decarboxylase autoantibody positive patient sera, and IgG (n = 3) from healthy blood donors. Effective complexing of TPO by TPO autoantibodies was tested by precipitating the complexes with solid phase protein A and measuring the TPO enzyme activity in the resulting supernatants. These studies showed that the TPO enzyme activity was not affected by incubation with TPO autoantibody-positive IgG or monoclonal antibodies despite effective complexing of the autoantibodies with TPO. Overall, our studies demonstrate that nTPO and rTPO produced in insect cells are very similar in terms of enzyme activity, UV and visible spectra, and reactivity with autoantibodies. Furthermore, in our study, TPO autoantibodies did not appear to inhibit TPO enzyme activity.

The interaction of TSH receptor autoantibodies with 125I-labelled TSH receptor.

Detergent-solubilized porcine TSH receptor (TSHR) has been labeled with 125I using a monoclonal antibody to the C-terminal domain of the receptor. The ability of sera containing TSHR autoantibody to immunoprecipitate the labeled receptor was then investigated. Sera negative for TSHR autoantibody (as judged by assays based on inhibition of labeled TSH binding to detergent-solubilized porcine TSHR) immunoprecipitated about 4% of the labeled receptor, whereas sera with high levels of receptor autoantibody immunoprecipitated more than 25% of the labeled receptor. The ability to immunoprecipitate labeled TSHR correlated well with ability of the sera to inhibit labeled TSH binding to the receptor (r = 0.92; n = 63), and this is consistent with TSHR autoantibodies in these samples being directed principally to a region of the receptor closely related to the TSH binding site. Preincubation of labeled TSHR with unlabeled TSH before reaction with test sera inhibited the immunoprecipitation reaction, providing further evidence for a close relationship between the TSHR autoantibody binding site(s) and the TSH binding site. This was the case whether the sera had TSH agonist (i.e., thyroid stimulating) or TSH antagonist (i.e., blocking) activities, thus, providing no clear evidence for different regions of the TSHR being involved in forming the binding site(s) for TSHR autoantibodies with stimulating and with blocking activities. The ability of TSHR autoantibodies to stimulate cyclic AMP production in isolated porcine thyroid cells was compared with their ability to immunoprecipitate labeled porcine TSHR. A significant correlation was observed (r = 0.58; n = 50; P < 0.001) and the correlation was improved when stimulation of cyclic AMP production was compared with inhibition of labeled TSH binding to porcine TSHR (r = 0.76). Overall, our results indicate that TSHR autoantibodies bind principally to a region on the TSHR closely related to the TSH binding site, and this seems to be the case whether the autoantibodies act as TSH agonists or antagonists.

Thyrotropin (TSH) receptor autoantibodies do not appear to bind to the TSH receptor produced in an in vitro transcription/translation system.

An in vitro transcription/translation (TnT) system was used to produce 35S-labeled full-length TSH receptor (TSHR) and TSHR extracellular domain (TSHRex). The interaction of the labeled proteins with TSHR autoantibodies in Graves' sera was then studied using an immunoprecipitation assay. In the assay, 35S-labeled TSHR or TSHRex were incubated with test sera, and any immune complexes formed were precipitated with protein A-Sepharose (in the case of mouse monoclonal antibodies, antimouse IgG-agarose was used). Rabbit antibodies to the TSHR and a mouse monoclonal antibody precipitated as much as 50% of the 35S-labeled TSHR preparations compared with about 2% for normal rabbit serum and 4% for a control monoclonal antibody. However, none of 34 Graves' sera (TSHR autoantibody levels ranging from 14-95% inhibition of [125I]TSH binding) were able specifically to immunoprecipitate 35S-labeled TSHR or TSHRex. These negative findings were confirmed by analysis of the immunoprecipitates on SDS-PAGE followed by autoradiography. Our results indicate that the TnT system is not useful for producing labeled TSHR preparations that can bind TSHR autoantibodies well. This is in contrast to TnT produced 35S-labeled glutamic acid decarboxylase, thyroid peroxidase, and 21-hydroxylase, which react well with their respective autoantibodies. One main difference between these 3 autoantigens and the TSHR is that the receptor is highly glycosylated, and this extensive glycosylation may be of critical importance for correct folding of the receptor. Consequently, the inability of the TnT system to glycosylate proteins could explain in part why TnT-produced 35S-labeled TSHR and TSHRex do not bind TSHR autoantibodies.

Vanadium inhibition of human parietal lobe ATPases.

In vitro influence of vanadate and vanadyl ions on the activities of Na,K- and Ca,Mg-ATPase from synaptosomal membranes of the parietal lobe of the human brain were compared. 1. Vanadate and vanadyl inhibit the enzymes activities in the investigated fraction. 2. Vanadate is a more effective inhibitor of both ATPases in the concentrations above 50 microM and vanadyl is an effective inhibitor in a very low concentration (10 nM). 3. Vanadate seems to be an uncompetitive inhibitor of Na,K-ATPase (K1 = 880 nM).

[Hyponatremia after subarachnoid hemorrhage caused by ruptured intracranial aneurysm]. / Hiponatremia u chorych po krwotoku podpajeczynówkowym z peknietego tetniaka wewnatrzczaszkowego.

Hyponatremia developed both prior to and after surgery in 30.5% and 23.4% out of 164 patients with ruptured intracranial aneurysms. It was more frequent postoperatively in those patients in whom baseline serum sodium levels were lower. Hyponatremic patients were older than normonatremic. The mean difference in age was about 7 years. The authors, basing on CT scans, have found that hyponatremia development has been more likely in patients with blood visible in subarachnoid space, specially chiasmatic cistern, and patients with ventricular bleeding or hydrocephalus. Hyponatremia following subarachnoid hemorrhage seems to result from the ischemic lesions to hypothalamus i may, therefore, be considered as vegetative equivalent of so-called cerebrovascular spasm.

[Computerized tomography in the diagnosis of hemorrhage caused by ruptured intracranial aneurysm]. / Tomografia komputerowa w rozpoznawaniu krwawienia z peknietego tetniaka wewnatrzczaszkowego.

The authors presented current views on usefulness of computed tomography (CT) for diagnosing the bleeding from a ruptured intracranial aneurysm. CT should be done in every such case, whereas the lumbar puncture remains the diagnostic method of choice, when CT is not available or in those patients in whom CT shows no haemorrhage. Sensitivity of CT decreases with time that elapsed from the stroke; false negative results are the least likely to occur within the first 48 hours after bleeding episode to subarachnoid space.

[Various problems related to the occurrence of hydrocephalus after subarachnoid hemorrhage caused by ruptured cerebral aneurysm]. / Niektóre zagadnienia zwiazane z pojawieniem sie wodoglowia po krwotoku podpajeczynówkowym z peknietego tetniaka naczyn mózgowych.

A CT scan done on admission showed widening of the ventricular system in 56 (34%) out of 164 patients with a ruptured intracranial aneurysm. 82% of the patients were admitted within 5 days after the bleeding. Those with hydrocephalus were often in a poor clinical condition (grades 3-5 Hunt and Hess, p less than 0.01) with up-going plantars twice as frequently encountered as in the remaining group. Widening of the ventricles adversely affected the prognosis. With hydrocephalus rebleeding was more frequent (p less than 0.02) and so was the ischaemic neurological deficit, whereas long-term treatment results were worse (p less than 0.01) with a double mortality rate (p less than 0.02). Hydrocephalus was more frequent in older patients (p less than 0.001 and in those with posterior fossa aneurysms (p less than 0.005). It was also promoted by diffuse and extensive bleeding into the subarachnoid space (p less than 0.01) and by intraventricular haemorrhage (p less than 0.0001). Three patients were treated with ventricular drainage.