Percutaneous transosseous translaminar approach for thecal sac access in advanced ankylosing spondylitis with instrumented posterior spinal fusion.

A novel transosseous approach for percutaneous access of the lumbar subarachnoid space is described in a patient with advanced ankylosing spondylitis (AS) and instrumented spinal fusion who presented for myelography. Use of a coaxial threaded bone biopsy system to provide transosseous access to the thecal sac, imaging findings, and outcome are discussed. This technique provided access to an otherwise inaccessible subarachnoid space and is an alternative approach in the setting of advanced AS or posterior spinal fusion.

Emergent image-guided treatment of a large CSF leak to reverse "in-extremis" signs of intracranial hypotension.

We report the use of an emergent, targeted fibrin spinal epidural blood patch with subarachnoid saline infusion to rapidly reverse "in-extremis" clinical and imaging signs of posterior-fossa coning brought about by acute-on-chronic intracranial hypotension, itself consequent to a cervicothoracic CSF leak. Treatment resulted in a dramatic recovery and eventual discharge with return to normal lifestyle and occupation. The clinical and imaging danger signs are reviewed; fibrin patch technique and potential pitfalls in postprocedure management are analyzed.

Time-resolved spinal MR angiography: initial clinical experience in the evaluation of spinal arteriovenous shunts.

BACKGROUND AND PURPOSE: Spinal arteriovenous shunts usually require digital subtraction angiography (DSA) for evaluation. We report a unique time-resolved spinal MR angiographic (TRSMRA) technique with a temporal resolution of 3-6 seconds and spatial resolution of approximately 1 mm(3) that has the potential to noninvasively detect, localize, and follow-up these cases. MATERIALS AND METHODS: Eleven patients with clinical presentation and/or MR findings suspicious for a spinal arteriovenous shunt were referred for TRSMRA. Patients subsequently underwent spinal DSA to confirm the presence or absence of a shunt or were followed clinically until an alternative diagnosis was found. TRSMRA was also used to predict the level of the shunt in the positive cases. In addition, 2 of these patients as well as a 12th patient referred to us posttreatment received a follow-up TRSMRA to assess treatment outcome. RESULTS: Early venous shunting was identified by using TRSMRA in 6 cases. All 6 were confirmed to have an AV shunt on subsequent spinal DSA. The shunt level predicted by TRSMRA consistently correlated with DSA to within 1 vertebral level. In the 5 patients with a negative screening TRSMRA, DSA or clinical outcome confirmed the absence of an arteriovenous shunt in all of the cases. Posttreatment TRSMRA in 3 patients accurately assessed the success or failure of treatment. CONCLUSION: Combining acceleration techniques to achieve high frame rate TRSMRA provides sufficient temporal and spatial resolution to identify, localize, and follow patients suspected of having a spinal arteriovenous shunt. Further study in a larger population is warranted to assess the accuracy of this technique.

Spinal arteriovenous malformations associated with Klippel-Trenaunay-Weber syndrome: a literature search and report of two cases.

SUMMARY: Patients with Klippel-Trenaunay-Weber syndrome present with venous varices, cutaneous capillary malformations, and tissue hypertrophy, usually involving an extremity. A small but important subset also harbors arteriovenous malformations (AVMs) of the spine. We report 2 such cases, 1 with 3 concurrent spinal arteriovenous fistulas. These cases and our review of the literature emphasize the importance of screening the spine for AVMs. In addition, it is also important to investigate for the presence of multiple spinal AVMs.

Intracranial time-resolved contrast-enhanced MR angiography at 3T.

BACKGROUND AND PURPOSE: A method is presented for high-temporal-resolution MR angiography (MRA) using a combination of undersampling strategies and a high-field (3T) scanner. Currently, the evaluation of cerebrovascular disorders involving arteriovenous shunting or retrograde flow is accomplished with conventional radiographic digital subtraction angiography, because of its high spatial and temporal resolutions. Multiphase MRA could potentially provide the same diagnostic information noninvasively, though this is technically challenging because of the inherent trade-off between signal intensity-to-noise ratio (S/N), spatial resolution, and temporal resolution in MR imaging. METHODS: Numerical simulations addressed the choice of imaging parameters at 3T to maximize S/N and the data acquisition rate while staying within specific absorption rate limits. The increase in S/N at 3T was verified in vivo. An imaging protocol was developed with S/N, spatial resolution, and temporal resolution suitable for intracranial angiography. Partial Fourier imaging, parallel imaging, and the time-resolved echo-shared acquisition technique (TREAT) were all used to achieve sufficient undersampling. RESULTS: In 40 volunteers and 10 patients exhibiting arteriovenous malformations or fistulas, intracranial time-resolved contrast-enhanced MRA with high acceleration at high field produced diagnostic-quality images suitable for assessment of pathologies involving arteriovenous shunting or retrograde flow. The technique provided spatial resolution of 1.1 x 1.1 x 2.5 mm and temporal resolution of 2.5 seconds/frame. The combination of several acceleration methods, each with modest acceleration, can provide a high overall acceleration without the artifacts of any one technique becoming too pronounced. CONCLUSION: By taking advantage of the increased S/N provided by 3T magnets over conventional 1.5T magnets and converting this additional S/N into higher temporal resolution through acceleration strategies, intracranial time-resolved MRA becomes feasible.

Sex-specific association between bipolar affective disorder in women and GPR50, an X-linked orphan G protein-coupled receptor.

GPR50 is an orphan G protein-coupled receptor (GPCR) located on Xq28, a region previously implicated in multiple genetic studies of bipolar affective disorder (BPAD). Allele frequencies of three polymorphisms in GPR50 were compared in case-control studies between subjects with BPAD (264), major depressive disorder (MDD) (226), or schizophrenia (SCZ) (263) and ethnically matched controls (562). Significant associations were found between an insertion/deletion polymorphism in exon 2 and both BPAD (P=0.0070), and MDD (P=0.011) with increased risk associated with the deletion variant (GPR50(Delta502-505)). When the analysis was restricted to female subjects, the associations with BPAD and MDD increased in significance (P=0.00023 and P=0.0064, respectively). Two other single-nucleotide polymorphisms (SNPs) tested within this gene showed associations between: the female MDD group and an SNP in exon 2 (P=0.0096); and female SCZ and an intronic SNP (P=0.0014). No association was detected in males with either MDD, BPAD or SCZ. These results suggest that GPR50(Delta502-505), or a variant in tight linkage disequilibrium with this polymorphism, is a sex-specific risk factor for susceptibility to bipolar disorder, and that other variants in the gene may be sex-specific risk factors in the development of schizophrenia.

Cerebellar pleomorphic xanthoastrocytoma in a patient with neurofibromatosis type 1.

We describe a case of cerebellar pleomorphic xanthoastrocytoma (PXA) occurring in a patient with neurofibromatosis type 1 (NF1). The histomorphology of this uncommon glial (astrocytic) neoplasm is discussed. The occurrence of this tumor within the posterior fossa is extremely rare. To our knowledge, this is the first reported case of a cerebellar PXA in a patient with NF1.

Intradural primary chondroblastic osteosarcoma: case report.

We report a rare case of intradural primary osteosarcoma (IPOS) in a 74-year-old man with aphasia and right-sided hemiparesis. Radiologic workup revealed a large, partially calcified, left-sided frontotemporal intracranial mass lesion. At surgery, the tumor was found to be entirely intradural; it involved the brain and subarachnoid space of the left sylvian fissure. The adjacent dura was uninvolved. Neuropathologic findings confirmed the diagnosis of chondroblastic osteosarcoma. To our knowledge, this is the sixth reported case of IPOS and the first reported case of the chondroblastic subtype.

Schizophrenia and affective disorders--cosegregation with a translocation at chromosome 1q42 that directly disrupts brain-expressed genes: clinical and P300 findings in a family.

A family with a (1;11)(q42;q14.3) translocation significantly linked to a clinical phenotype that includes schizophrenia and affective disorders is described. This translocation generates a LOD score of 3.6 when the disease phenotype is restricted to schizophrenia, of 4.5 when the disease phenotype is restricted to affective disorders, of 7.1 when relatives with recurrent major depression, with bipolar disorder, or with schizophrenia are all classed as affected. This evidence for linkage is among the strongest reported for a psychiatric disorder. Family members showed no distinctive features by which the psychiatric phenotype could be distinguished from unrelated cases of either schizophrenia or affective disorders, and no physical, neurological, or dysmorphic conditions co-occurred with psychiatric symptoms. Translocation carriers and noncarriers had the same mean intelligence quotient. Translocation carriers were similar to subjects with schizophrenia and different from noncarriers and controls, in showing a significant reduction in the amplitude of the P300 event-related potential (ERP). Furthermore, P300 amplitude reduction and latency prolongation were measured in some carriers of the translocation who had no psychiatric symptoms-a pattern found in other families with multiple members with schizophrenia, in which amplitude of and latency of P300 appear to be trait markers of risk. The results of karyotypic, clinical, and ERP investigations of this family suggest that the recently described genes DISC1 and DISC2, which are directly disrupted by the breakpoint on chromosome 1, may have a role in the development of a disease phenotype that includes schizophrenia as well as unipolar and bipolar affective disorders.

Touch-preparation cytologic examination of breast core biopsy specimens: accuracy in predicting benign or malignant core histologic results.

RATIONALE AND OBJECTIVES: The purpose of this study was to determine the accuracy of touch-preparation cytologic examination of breast core biopsy specimens in predicting benign or malignant core histologic results. MATERIALS AND METHODS: One hundred two core biopsies were performed on 88 women with stereotactic or ultrasonographic (US) guidance. Slides were prepared by smearing one core sample on each slide, spraying the slides with fixative, and staining them with the Papanicolaou technique. Slides were blindly reviewed by a cytopathologist. Cytologic results were categorized as positive for malignancy, not diagnostic for malignancy, or insufficient for diagnosis. Results were correlated with histologic results from all specimens obtained during the core biopsy. RESULTS: Imaging depicted the lesions sampled for biopsy as masses (n = 70), clustered calcifications (n = 29), focal asymmetries (n = 2), or architectural distortion (n = 1). Touch-preparation slides of 87 (85%) lesions contained sufficient material for diagnosis. Cytologic results correctly identified 12 of 16 (three of five intraductal and nine of 11 invasive) malignancies in 10 of 13 masses and two of three clusters of calcifications. Two false-positive results occurred, both with fibroadenomas. Overall, touch-preparation studies produced 69 true-negative and four false-negative results. Excluding slides with insufficient material, the sensitivity, specificity, and accuracy of touch-preparation results were 75%, 97%, and 93%, respectively. Including insufficient samples, accuracy was 79%. CONCLUSION: Although touch-preparation cytologic examination of breast core biopsy specimens is fairly accurate in prediction of benign or malignant core histologic results, its correlation with histologic results is not sufficient to justify routine use in immediate counseling and treatment planning.

Limb salvage surgery in spinal cord injury patients.

Advances in the care and rehabilitation of patients with spinal cord injuries (SCI) have resulted in extended survival following injury. Increasingly, we are faced with difficult chronic lower extremity ischemic complications in SCI patients. Recognizing limitations associated with amputation in these nonambulatory patients, we report the preliminary results of a program of selective limb salvage via arterial reconstructive surgery. Retrospective chart review was performed on the records of the Veterans Affairs Palo Alto Health Care System SCI unit. Since 1989, 15 revascularization procedures were identified in 10 SCI patients. All patients suffered from ischemic ulceration and/or gangrene. Procedures performed included femorotibial bypass (8), aortofemoral bypass (4), femoro-femoral bypass (2), and axillobifemoral bypass (AXF) (1). All patients were men. The mean age was 56 (range 43-73). Follow-up was available on 10 procedures performed in seven patients since 1992. Mean follow-up was 17 months. One patient died 3 months following distal bypass. The AXF occluded within 1 month. One distal bypass occluded in the immediate postoperative period and could not be salvaged. All other grafts remain patent, and all wounds have healed following successful bypass. One patient developed pressure ulceration following AXF grafting due to postoperative upper extremity limitations. No other complications were encountered. Standard arterial reconstructive procedures can be performed safely and successfully in SCI patients, despite diminished limb blood flow due to inactivity, and atrophic arteries, muscle, and fascia. Axillobifemoral bypass grafting may not be suitable in SCI due to requirements for upper extremity-based mobility. Confirmation of benefit of limb salvage versus amputation awaits comparison between patients eligible for either procedure.

Implications of comorbidity for genetic studies of bipolar disorder: P300 and eye tracking as biological markers for illness.

In large families with affective illness, identification of a biological variable is needed that reflects brain dysfunction at an earlier point than symptom development. Eye movement disorder, a possible vulnerability marker in schizophrenia, is less clearly associated with affective illness, although a subgroup of affective disorders shows smooth-pursuit eye movement disorder. The auditory P300 event-related potential may be a useful marker for risk to schizophrenia, but a role in bipolar illness is less certain. The distribution of these two biological variables and their association with symptoms in two multiply affected bipolar families is described. In a single, five-generation family identified for linkage studies through two bipolar I (BPI) probands, 128 members (including 20 spouses) were interviewed. The 108 related individuals had diagnoses of BPI (7), bipolar II (2), cyclothymia (3), or major depressive disorder (19). Eight others had generalised anxiety (1), minor depression (5), intermittent depression (1), or alcoholism (1). Sixty-nine subjects had no psychiatric diagnosis. P300 latency (81) and eye tracking (71) were recorded from a subgroup of relatives within the pedigree. Eye tracking was abnormal in 11 of 71 relatives (15.5%) and was bimodally distributed. In these 11 relatives, clinical diagnoses included minor depression (1), alcoholism (1) and generalised anxiety disorder (1). P300 latency was normally distributed and did not differ from controls. In a second family in which five of seven siblings have BPI illness, P300 latency and eye movement disorder were found in affected relatives and in some unaffected offspring. In these large families, clinical diagnoses of general anxiety, alcoholism and minor depression, when associated with eye tracking abnormality, may be considered alternative clinical manifestations of the same trait that in other relatives is expressed as bipolar illness.

A locus for bipolar affective disorder on chromosome 4p.

The main clinical feature of bipolar affective disorder is a change of mood to depression or elation. Unipolar disorder, also termed major depressive disorder, describes the occurrence of depression alone without episodes of elevated mood. Little is understood about the underlying causes of these common and severe illnesses which have estimated lifetime prevalences in the region of 0.8% for bipolar and 6% for unipolar disorder. Strong support for a genetic aetiology is found in the familial nature of the condition, the increased concordance of monozygotic over dizygotic twins and adoption studies showing increased rates of illness in children of affected parents. However, linkage studies have met with mixed success. An initial report of linkage on the short arm of chromosome 11 (ref. 4) was revised and remains unreplicated. Reports proposing cosegregation of genes found on the X chromosome with bipolar illness have not been supported by others. More recently bipolar disorder has been reported to be linked with markers on chromosomes 18, 21, 16 and a region on the X chromosome different from those previously suggested. We have carried out a linkage study in twelve bipolar families. In a single family a genome search employing 193 markers indicated linkage on chromosome 4p where the marker D4S394 generated a two-point lod score of 4.1 under a dominant model of inheritance. Three point analyses with neighbouring markers gave a maximum lod score of 4.8. Eleven other bipolar families were typed using D4S394 and in all families combined there was evidence of linkage with heterogeneity with a maximum two-point lod score of 4.1 (theta = 0, alpha = 0.35).

Auditory P300 event-related potentials and neuropsychological performance in schizophrenia and bipolar affective disorder.

The auditory P300 event-related potential (ERP) and performance on neuropsychological tests were evaluated in 26 subjects with schizophrenia, 19 with bipolar affective disorder, and 27 controls. The schizophrenic and the bipolar groups were similar in having prolonged P300 latency recorded from central and temporal leads. The P300 was significantly reduced in amplitude in the schizophrenic group at midline leads and the left temporal lead but was not significantly reduced in amplitude at any electrode site when the bipolar group was compared to controls. Schizophrenics performed significantly less well than bipolars and controls on tests of verbal fluency and, within this group, a significant correlation was found between the latency of P300 and verbal fluency test scores. While the bipolar group of patients was similar to the schizophrenic group in having prolonged P300 latency, these groups differed in P300 amplitude, performance on verbal fluency tests, and the relationship between the physiological and neuropsychological variables.

Methodological considerations in measurement of the P300 component of the auditory oddball ERP in schizophrenia.

Twenty-three schizophrenic patients and 26 age-matched control subjects were studied using the P300 recorded during the auditory oddball task, with counting. Our aim was to assess the most suitable method of measurement and analysis of P300 amplitude and latency for use in clinical studies of schizophrenia. The effect of high-pass filtering, peak definition method and recording electrode site were all investigated. We have developed a technique, based on a least-mean-squares approximation to data, which seems particularly well suited to dealing with multi-peak P300 complexes. We have also investigated the spectral composition of the P300 and have found some evidence to support a proposed 2-frequency model of the P300 complex.

Neuropsychological and P300 abnormalities in schizophrenics and their relatives.

Schizophrenic subjects (N = 30) performed less well than controls (N = 30) on neuropsychological tests sensitive to frontal and temporal lobe impairment and showed prolonged latency of the P300 event-related potential. Relatives of schizophrenic probands were also tested. Relatives with an abnormal P300 had a similar range of neuropsychological deficits as were found in the schizophrenic group and relatives with a normal P300 response performed as well as the normal control group. The results suggest that neurophysiological and neuropsychological testing of relatives may help to clarify the mode of inheritance of schizophrenia in some families.