Recovery of oculomotor nerve palsy secondary to posterior communicating artery aneurysms.

BACKGROUND: Recent studies suggest more favourable recovery of oculomotor nerve palsy (ONP) caused by posterior communicating artery (PComA) aneurysms with microsurgical clipping compared to endovascular coiling. We describe a consecutive series of patients with ONP from PComA aneurysms treated by microsurgical clipping or endovascular coiling. METHODS: We retrospectively reviewed medical records of all patients from 2005 to 2009 with complete or partial ONP from PComA aneurysms. RESULTS: Twenty patients were identified, three with unruptured aneurysms. Two patients with ruptured aneurysms were unfit for treatment and therefore excluded. Of the 18 patients included (15 female), 9 underwent microsurgical clipping and 9 received endovascular coiling. Patients treated by surgical clipping were significantly younger compared to those treated by endovascular coiling (mean 52.3 vs. 67.9 years; p = 0.039). Five patients had incomplete ONP (3 clipped, 2 coiled) and thirteen had complete ONP. At 6 months, six of nine patients treated with clipping and five of nine patients treated with coiling had complete resolution of their ONP (p = 1.0); the remainder had partial improvement. There was no significant difference in duration of pre-treatment ONP, age, sex or status of aneurysm (ruptured or unruptured) between patients in the two groups or between those with full or partial recovery. However, all 5 patients with incomplete ONP at presentation recovered fully, compared with 6 of 13 patients who presented with complete ONP. CONCLUSIONS: We found no significant difference between clipping and coiling in the recovery of ONP due to PComA aneurysms. Patient who present with incomplete ONP are more likely to have a full recovery of ONP following either treatment modality than those who present with complete ONP.

Fluid intelligence loss linked to restricted regions of damage within frontal and parietal cortex.

Tests of fluid intelligence predict success in a wide range of cognitive activities. Much uncertainty has surrounded brain lesions producing deficits in these tests, with standard group comparisons delivering no clear result. Based on findings from functional imaging, we propose that the uncertainty of lesion data may arise from the specificity and complexity of the relevant neural circuit. Fluid intelligence tests give a characteristic pattern of activity in posterolateral frontal, dorsomedial frontal, and midparietal cortex. To test the causal role of these regions, we examined fluid intelligence in 80 patients with focal cortical lesions. Damage to each of the proposed regions predicted fluid intelligence loss, whereas damage outside these regions was not predictive. The results suggest that coarse group comparisons (e.g., frontal vs. posterior) cannot show the neural underpinnings of fluid intelligence tests. Instead, deficits reflect the extent of damage to a restricted but complex brain circuit comprising specific regions within both frontal and posterior cortex.

Acute ischaemic brain lesions in intracerebral haemorrhage: multicentre cross-sectional magnetic resonance imaging study.

Subclinical acute ischaemic lesions on brain magnetic resonance imaging have recently been described in spontaneous intracerebral haemorrhage, and may be important to understand pathophysiology and guide treatment. The underlying mechanisms are uncertain. We tested the hypothesis that ischaemic lesions are related to magnetic resonance imaging markers of the severity and type of small-vessel disease (hypertensive arteriopathy or cerebral amyloid angiopathy) in a multicentre, cross-sectional study. We studied consecutive patients with intracerebral haemorrhage from four specialist stroke centres, and age-matched stroke service referrals without intracerebral haemorrhage. Acute ischaemic lesions were assessed on magnetic resonance imaging (<3 months after intracerebral haemorrhage) using diffusion-weighted imaging. White matter changes and cerebral microbleeds were rated with validated scales. We investigated associations between diffusion-weighted imaging lesions, clinical and radiological characteristics. We included 114 patients with intracerebral haemorrhage (39 with clinically probable cerebral amyloid angiopathy) and 47 age-matched controls. The prevalence of diffusion-weighted imaging lesions was 9/39 (23%) in probable cerebral amyloid angiopathy-related intracerebral haemorrhage versus 6/75 (8%) in the remaining patients with intracerebral haemorrhage (P = 0.024); no diffusion-weighted imaging lesions were found in controls. Diffusion-weighted imaging lesions were mainly cortical and were associated with mean white matter change score (odds ratio 1.14 per unit increase, 95% confidence interval 1.02-1.28, P = 0.024) and the presence of strictly lobar cerebral microbleeds (odds ratio 3.85, 95% confidence interval 1.15-12.93, P = 0.029). Acute, subclinical ischaemic brain lesions are frequent but previously underestimated after intracerebral haemorrhage, and are three times more common in cerebral amyloid angiopathy-related intracerebral haemorrhage than in other intracerebral haemorrhage types. Ischaemic brain lesions are associated with white matter changes and cerebral microbleeds, suggesting that they result from an occlusive small-vessel arteriopathy. Diffusion-weighted imaging lesions contribute to the overall burden of vascular-related brain damage in intracerebral haemorrhage, and may be a useful surrogate marker of ongoing ischaemic injury from small-vessel damage.

Infarction of 'non-core-non-penumbral' tissue after stroke: multivariate modelling of clinical impact.

There is considerable intersubject variability in early neurological course after anterior circulation stroke, yet the pathophysiology underlying this variability is not fully understood. Here, we hypothesize that, although not predicted by current pathophysiological models, infarction of 'non-core-non-penumbral' (i.e. clinically silent) brain tissue may nevertheless occur, and negatively influence clinical course over and above the established positive impact of penumbral salvage. In order to test this hypothesis, non-core-non-penumbral tissue was identified in two independent prospectively recruited cohorts, using computed tomography perfusion, and magnetic resonance perfusion- and diffusion-weighted imaging, respectively. Follow-up structural magnetic resonance imaging was obtained about 1 month later in all patients to map the final infarct. The volumes of both the acutely silent but eventually infarcted tissue, and the eventually non-infarcted penumbra, were determined by performing voxel-wise analysis of the acute and follow-up image sets, using previously validated perfusion thresholds. Early neurological course was expressed as change in National Institutes of Health Stroke Scale scores between the acute and 1-month assessments, relative to the acute score. The relationship between the acutely silent but eventually infarcted tissue volume and early neurological course was tested using a multivariate regression model that included the volume of non-infarcted penumbra. Thirty-four and 58 patients were recruited in the computed tomography perfusion and magnetic resonance perfusion cohorts, respectively (mean onset-to-imaging time: 136 and 156 min; 27 and 42 patients received intravenous thrombolysis, respectively). Infarction of acutely silent tissue was identified in most patients in both cohorts. Although its volume (median 0.2 and 2 ml, respectively) was much smaller than that of salvaged penumbra (59.3 and 93 ml, respectively), it was substantial in ∼10% of patients. As expected, salvaged penumbra strongly positively influenced early neurological course. Even after correcting for the latter effect in the multivariate model, infarction of acutely silent tissue independently negatively influenced early neurological course in both cohorts (P=0.018 and 0.031, respectively). This is the first systematic study to document infarction of acutely silent tissue after anterior circulation stroke, and to show that it affects a sizeable fraction of patients and has the predicted negative impact on clinical course. These findings were replicated in two independent cohorts, regardless of the perfusion imaging modality used. Preventing infarction of the tissue not initially at risk should have direct clinical benefit.

Executive function and fluid intelligence after frontal lobe lesions.

Many tests of specific 'executive functions' show deficits after frontal lobe lesions. These deficits appear on a background of reduced fluid intelligence, best measured with tests of novel problem solving. For a range of specific executive tests, we ask how far frontal deficits can be explained by a general fluid intelligence loss. For some widely used tests, e.g. Wisconsin Card Sorting, we find that fluid intelligence entirely explains frontal deficits. When patients and controls are matched on fluid intelligence, no further frontal deficit remains. For these tasks too, deficits are unrelated to lesion location within the frontal lobe. A second group of tasks, including tests of both cognitive (e.g. Hotel, Proverbs) and social (Faux Pas) function, shows a different pattern. Deficits are not fully explained by fluid intelligence and the data suggest association with lesions in the right anterior frontal cortex. Understanding of frontal lobe deficits may be clarified by separating reduced fluid intelligence, important in most or all tasks, from other more specific impairments and their associated regions of damage.

Magnetic resonance imaging changes in the pituitary gland following acute traumatic brain injury.

OBJECTIVE: The objective was to study the anatomical changes in the pituitary gland following acute moderate or severe traumatic brain injury (TBI). DESIGN: Retrospective, observational, case-control study. SETTING: Neurosciences Critical Care Unit of a university hospital. PATIENTS: Forty-one patients with moderate or severe TBI who underwent magnetic resonance imaging (MRI) during the acute phase (less than seven days) of TBI. MRI scans of 43 normal healthy volunteers were used as controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient demographics, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Injury Severity Score (ISS), post-resuscitation Glasgow Coma Score (GCS), Glasgow Outcome Score (GOS), mean intracranial pressure (ICP), mean cerebral perfusion pressure (CPP), computed tomography (CT) data, pituitary gland volumes and structural lesions in the pituitary on MRI scans. The pituitary glands were significantly enlarged in the TBI group (the median and interquartile range were as follows: cases 672 mm3 (range 601-783 mm3) and controls 552 mm3 (range 445-620 mm3); p value<0.0001). APACHE II, GCS, GOS and ICP were not significantly correlated with the pituitary volume. Twelve of the 41 cases (30%) demonstrated focal changes in the pituitary gland (haemorrhage/haemorrhagic infarction (n=5), swollen gland with bulging superior margin (n=5), heterogeneous signal intensities in the anterior lobe (n=2) and partial transection of the infundibular stalk (n=1). CONCLUSIONS: Acute TBI is associated with pituitary gland enlargement with specific lesions, which are seen in approximately 30% of patients. MRI of the pituitary may provide useful information about the mechanisms involved in post-traumatic hypopituitarism.

A rare presentation of ventriculitis and brain abscess caused by Fusobacterium nucleatum.

Anaerobic ventriculitis is rare, and usually seen in patients with predisposing factors such as otitis media, mastoiditis, sinusitis or recent neurosurgery. We report what we believe to be the first case of ventriculitis and brain abscess due to Fusobacterium nucleatum infection in a man with no significant predisposing factors. He was successfully treated with antibiotic therapy.

Eyelid apraxia associated with bilateral paramedian thalamic infarct.

We report a case of bilateral thalamic infarct associated with bilateral eyelid apraxia. This extremely rare condition provides us with an opportunity to map clinical and neuroimaging findings to help better understand brain function.

High grade glioma: imaging combined with pathological grade defines management and predicts prognosis.

INTRODUCTION: There is ambiguity in pathological grading of high grade gliomas within the WHO 2000 classification, especially those with predominant oligodendroglial differentiation. PATIENTS AND METHODS: All adult high grade gliomas treated radically, 1996-2005, were assessed. Cases in which pathology was grade III but radiology suggested glioblastoma (GBM) were classified as 'grade III/IV'; their pathology was reviewed. RESULTS: Data from 245 patients (52 grade III, 18 grade III/IV, 175 GBM) were analysed using a Cox Proportional Hazards model. On pathology review, features suggestive of more aggressive behaviour were found in all 18 grade III/IV tumours. Oligodendroglial components with both necrosis and microvascular proliferation were present in 7. MIB-1 counts for the last 8 were all above 14%, mean 27%. Median survivals were: grade III 34 months, grade III/IV 10 months, GBM 11 months. Survival was not significantly different between grade III/IV and GBM. Patients with grade III/IV tumours had significantly worse outcome than grade III, with a hazard of death 3.7 times higher. CONCLUSIONS: The results highlight the current inconsistency in pathological grading of high grade tumours, especially those with oligodendroglial elements. Patients with histological grade III tumours but radiological appearances suggestive of GBM should be managed as glioblastoma.

Clinical Experience and Results of Microsurgical Resection of Arterioveonous Malformation in the Presence of Space-Occupying Intracerebral Hematoma.

BACKGROUND: Management of ruptured arteriovenous malformations (AVMs) with a mass-producing intracerebral hematoma (ICH) represents a surgical dilemma. OBJECTIVE: To evaluate the clinical outcome and obliteration rates of microsurgical resection of AVM when performed concomitantly with evacuation of an associated space-occupying ICH. METHODS: Data of patients with AVM were collected prospectively. Cases were identified in which an AVM was resected and an associated space-occupying ICH was evacuated at the same time, and divided into "group 1," in which the surgery was performed acutely within 48 h of presentation (secondary to elevated intracranial pressure); and "group 2," in which selected patients were operated upon in the presence of a liquefying ICH in the "subacute" stage. Clinical outcomes were assessed using the modified Rankin Scale, with a score of 0 to 2 considered a good outcome. Obliteration rates were assessed using postoperative angiography. RESULTS: From 2001 to 2015, 131 patients underwent microsurgical resection of an AVM, of which 65 cases were included. In "group 1" (n = 21; Spetzler-Ponce class A = 13, class B = 5, and class C = 3), 11 of 21 (52%) had a good outcome and in 18 of 19 (95%) of those who had a postoperative angiogram the AVMs were completely obliterated. In "group 2" (n = 44; Spetzler-Ponce class A = 33, class B = 9, and class C = 2), 31 of 44 (93%) had a good outcome and 42 of 44 (95%) were obliterated with a single procedure. For supratentorial AVMs, the ICH cavity was utilized to provide an operative trajectory to a deep AVM in 11 cases, and in 26 cases the ICH cavity was deep to the AVM and hence facilitated the deep dissection of the nidus. CONCLUSION: In selected patients the presence of a liquefying ICH cavity may facilitate the resection of AVMs when performed in the subacute stage resulting in a good neurological outcome and high obliteration rate.

Stroke attributable to a calcific embolus from the brachiocephalic trunk.

BACKGROUND AND PURPOSE: Calcific brain embolization is a rare event that is usually secondary to cardiac valve calcification. We present a case of stroke caused by embolization of calcific material from the brachiocephalic trunk, probably induced by radiotherapy. SUMMARY OF CASE: A 56-year-old right-handed female developed left-sided hemiparesis, hemihypesthesia, and sensory inattention. She had a history of right breast carcinoma that was excised 8 years previously followed by radiotherapy. She had no other history of note. Computed tomography of the head and magnetic resonance imaging confirmed a calcific embolus in right middle cerebral artery and an acute infarction in the corresponding territory. Plain chest radiography, carotid ultrasonography, transthoracic and transoesophageal echocardiography failed to demonstrate the source of calcific embolism. Computed tomography of the thorax revealed heavy calcification of the brachiocephalic trunk and the origin of the right common carotid artery. CONCLUSIONS: Undertaking a vigilant systematic search for the source in cases of calcific embolization is necessary. The aorta and its main branches are possible, yet unusual, sources of calcific emboli that merit investigation.

Bulbar dysfunction and aspiration pneumonia due to a brainstem haemangioblastoma: an unusual complication of von Hippel-Lindau disease.

A 44-year-old woman with a history of von Hippel-Lindau (VHL) disease, a rare inherited neoplasia syndrome, presented acutely to hospital with a productive cough, symptoms of respiratory tract infection and odynophagia (painful swallowing). A chest X-ray confirmed right-sided pneumonia. Investigation of the persistent odynophagia using barium swallow revealed aspiration of the contrast into the lungs and suggested a neurological cause for her chest infection. Clinical assessment and speech and language therapy confirmed a pseudobulbar palsy. Subsequent neuroimaging identified a cystic haemangioblastoma, located at the cervicomedullary junction of the brainstem, as the cause of the pseudobulbar palsy. Urgent neurosurgical excision produced symptomatic relief and with continuing medical therapy, and clinical resolution of her pneumonia. In patients with VHL disease and other inherited cancer syndromes, a high index of suspicion should be maintained for new tumours presenting with common medical symptoms and signs.

Successful treatment of residual pituitary adenoma in persistent acromegaly following localisation by 11C-methionine PET co-registered with MRI.

OBJECTIVE: To determine if functional imaging using 11C-methionine positron emission tomography co-registered with 3D gradient echo MRI (Met-PET/MRI), can identify sites of residual active tumour in treated acromegaly, and discriminate these from post-treatment change, to allow further targeted treatment. DESIGN/METHODS: Twenty-six patients with persistent acromegaly after previous treatment, in whom MRI appearances were considered indeterminate, were referred to our centre for further evaluation over a 4.5-year period. Met-PET/MRI was performed in each case, and findings were used to decide regarding adjunctive therapy. Four patients with clinical and biochemical remission after transsphenoidal surgery (TSS), but in whom residual tumour was suspected on post-operative MRI, were also studied. RESULTS: Met-PET/MRI demonstrated tracer uptake only within the normal gland in the four patients who had achieved complete remission after primary surgery. In contrast, in 26 patients with active acromegaly, Met-PET/MRI localised sites of abnormal tracer uptake in all but one case. Based on these findings, fourteen subjects underwent endoscopic TSS, leading to a marked improvement in (n = 7), or complete resolution of (n = 7), residual acromegaly. One patient received stereotactic radiosurgery and two patients with cavernous sinus invasion were treated with image-guided fractionated radiotherapy, with good disease control. Three subjects await further intervention. Five patients chose to receive adjunctive medical therapy. Only one patient developed additional pituitary deficits after Met-PET/MRI-guided TSS. CONCLUSIONS: In patients with persistent acromegaly after primary therapy, Met-PET/MRI can help identify the site(s) of residual pituitary adenoma when MRI appearances are inconclusive and direct further targeted intervention (surgery or radiotherapy).

A role for 11C-methionine PET imaging in ACTH-dependent Cushing's syndrome.

OBJECTIVE: We report our experience of functional imaging with (11)C-methionine positron emission tomography-computed tomography (PET-CT) co-registered with 3D gradient echo (spoiled gradient recalled (SPGR)) magnetic resonance imaging (MRI) in the investigation of ACTH-dependent Cushing's syndrome. DESIGN: Twenty patients with i) de novo Cushing's disease (CD, n=10), ii) residual or recurrent hypercortisolism following first pituitary surgery (±radiotherapy; n=8) or iii) ectopic Cushing's syndrome (n=2) were referred to our centre for functional imaging studies between 2010 and 2015. Six of the patients with de novo CD and five of those with persistent/relapsed disease had a suspected abnormality on conventional MRI. METHODS: All patients underwent (11)C-methionine PET-CT. For pituitary imaging, co-registration of PET-CT images with contemporaneous SPGR MRI (1 mm slice thickness) was performed, followed by detailed mapping of (11)C-methionine uptake across the sella in three planes (coronal, sagittal and axial). This allowed us to determine whether suspected adenomas seen on structural imaging exhibited focal tracer uptake on functional imaging. RESULTS: In seven of ten patients with de novo CD, asymmetric (11)C-methionine uptake was observed within the sella, which co-localized with the suspected site of a corticotroph microadenoma visualised on SPGR MRI (and which was subsequently confirmed histologically following successful transsphenoidal surgery (TSS)). Focal (11)C-methionine uptake that correlated with a suspected abnormality on pituitary MRI was seen in five of eight patients with residual or recurrent Cushing's syndrome following first TSS (and pituitary radiotherapy in two cases). Two patients elected to undergo repeat TSS with histology confirming a corticotroph tumour in each case. In two patients with the ectopic ACTH syndrome, (11)C-methionine was concentrated in sites of distant metastases, with minimal uptake in the sellar region. CONCLUSIONS: (11)C-methionine PET-CT can aid the detection of ACTH-secreting tumours in Cushing's syndrome and facilitate targeted therapy.

Measuring carotid stenosis on contrast-enhanced magnetic resonance angiography: diagnostic performance and reproducibility of 3 different methods.

BACKGROUND AND PURPOSE: The aim of this study was to compare diagnostic performance and reproducibility of 3 different methods of quantifying stenosis on contrast-enhanced magnetic resonance angiography (CEMRA), with intra-arterial digital subtraction angiography (DSA) as the reference standard. METHODS: 167 symptomatic patients scheduled for DSA, after screening Doppler ultrasound, were prospectively recruited to undergo CEMRA. Severity of stenosis was measured according to the North American Symptomatic Trial Collaborators (NASCET), European Carotid Surgery Trial (ECST), and the common carotid (CC) methods. Measurements for each method were made for 284 vessels (142 included patients) on both CEMRA and DSA in a blinded and randomized manner by 3 independent attending neuroradiologists. RESULTS: Significant differences in prevalence of severe stenosis were seen with the 3 methods on both DSA and CEMRA, with ECST yielding the least and NASCET the most cases of severe stenosis. Overall, all 3 methods performed similarly well in terms of intermodality correlation and agreement. No significant differences in interobserver agreement were found on either modality. With CEMRA, however, we found a significantly lower sensitivity for detection of severe stenosis with ECST (79.8%) compared with NASCET (93.0%), with DSA as reference standard. CONCLUSIONS: Uniformity of carotid stenosis measurement methods is desirable because patient management may otherwise differ substantially. All 3 methods are adequate for use with DSA. With CEMRA, however, this study supports use of the NASCET method because of improved sensitivity for detecting severe stenosis.

The contributions of lesion laterality and lesion volume to decision-making impairment following frontal lobe damage.

Lesions to prefrontal cortex (PFC) in humans can severely disrupt everyday decision-making, with concomitant effects on social and occupational functioning. Forty-six patients with unilateral lesions to prefrontal cortex and 21 healthy control subjects were administered three neuropsychological measures of decision-making: the Iowa Gambling Task, the Cambridge Gamble Task, and the Risk Task. Magnetic resonance imaging (MRI) scans were acquired from 40 patients, with region of interest (ROI) mapping of prefrontal subregions. The frontal patients showed only limited damage in medial and orbital prefrontal cortex, but greater damage in lateral prefrontal regions of interest. Patients with right frontal lesions preferred the risky decks on the Iowa Gambling Task, and differed significantly from left frontal and control subjects. Within the right frontal group, the preference for the risky decks was correlated with the total lesion volume and the volume of damage outside of the ventromedial prefrontal region. Right and left frontal groups did not differ significantly on the Cambridge Gamble Task or the Risk Task, and performance was not associated with lesion volume. The results indicate a laterality effect on the Iowa Gambling Task, and the contribution of prefrontal regions outside the ventromedial region to task performance. The Cambridge Gamble Task and Risk Task were less sensitive to the effects of unilateral frontal lobe lesions, and may be more selectively associated with ventral prefrontal damage.

The genome of the sparganosis tapeworm Spirometra erinaceieuropaei isolated from the biopsy of a migrating brain lesion.

BACKGROUND: Sparganosis is an infection with a larval Diphyllobothriidea tapeworm. From a rare cerebral case presented at a clinic in the UK, DNA was recovered from a biopsy sample and used to determine the causative species as Spirometra erinaceieuropaei through sequencing of the cox1 gene. From the same DNA, we have produced a draft genome, the first of its kind for this species, and used it to perform a comparative genomics analysis and to investigate known and potential tapeworm drug targets in this tapeworm. RESULTS: The 1.26 Gb draft genome of S. erinaceieuropaei is currently the largest reported for any flatworm. Through investigation of ß-tubulin genes, we predict that S. erinaceieuropaei larvae are insensitive to the tapeworm drug albendazole. We find that many putative tapeworm drug targets are also present in S. erinaceieuropaei, allowing possible cross application of new drugs. In comparison to other sequenced tapeworm species we observe expansion of protease classes, and of Kuntiz-type protease inhibitors. Expanded gene families in this tapeworm also include those that are involved in processes that add post-translational diversity to the protein landscape, intracellular transport, transcriptional regulation and detoxification. CONCLUSIONS: The S. erinaceieuropaei genome begins to give us insight into an order of tapeworms previously uncharacterized at the genome-wide level. From a single clinical case we have begun to sketch a picture of the characteristics of these organisms. Finally, our work represents a significant technological achievement as we present a draft genome sequence of a rare tapeworm, and from a small amount of starting material.

A comprehensive study of clinical, biochemical, radiological, vascular, cardiac, and sleep parameters in an unselected cohort of patients with acromegaly undergoing presurgical somatostatin receptor ligand therapy.

CONTEXT: Attainment of safe GH and IGF-1 levels is a central goal of acromegaly management. OBJECTIVE: The aim of this study was to determine the extent to which reductions in GH and IGF-1 concentrations correlate with amelioration of radiological, metabolic, vascular, cardiac, and respiratory sequelae in a single unselected patient cohort. STUDY DESIGN: This was a prospective, within-subject comparison in 30 patients with newly diagnosed acromegaly (15 women and 15 men: mean age, 54.3 years; range, 23-78 years) before and after 24 weeks of lanreotide Autogel (ATG) therapy. RESULTS: Reductions in GH and IGF-1 concentrations and tumor volume were observed in all but 2 patients (median changes [Δ]: GH, -6.88 µg/L [interquartile range -16.78 to -3.32, P = .000001]; IGF-1, -1.95 × upper limit of normal [-3.06 to -1.12, P = .000002]; and pituitary tumor volume, -256 mm(3) [-558 to -72.5, P = .0002]). However, apnea/hypopnea index scores showed highly variable responses (P = .11), which were independent of ΔGH or ΔIGF-1, but moderately correlated with Δweight (R(2) = 0.42, P = .0001). Although systolic (P = .33) and diastolic (P = .76) blood pressure were unchanged, improvements in arterial stiffness (aortic pulse wave velocity, -0.4 m/s [-1.2 to +0.2, P = .046]) and endothelial function (flow mediated dilatation, +1.73% [-0.32 to +6.19, P = .0013]) were observed. Left ventricular mass index regressed in men (-11.8 g/cm(2) [-26.6 to -1.75], P = .019) but not in women (P = .98). Vascular and cardiac changes were independent of ΔGH or ΔIGF-1 and also showed considerable interindividual variation. Metabolic parameters were largely unchanged. CONCLUSIONS: Presurgical ATG therapy lowers GH and IGF-1 concentrations, induces tumor shrinkage, and ameliorates/reverses cardiac, vascular, and sleep complications in many patients with acromegaly. However, responses vary considerably between individuals, and attainment of biochemical control cannot be assumed to equate to universal complication control.