Contrast-enhanced perfusion and diffusion MRI accurately lateralize temporal lobe epilepsy: a pilot study.

AIMS: To undertake a pilot study to assess whether magnetic resonance (MR) contrast-enhanced perfusion imaging (CEPI) and diffusion-weighted imaging (DWI) provide lateralizing information in medically refractory temporal lobe epilepsy (TLE),and to compare this to standard quantitative hippocampal assessments (volumetric measurements and T2 relaxometry). METHODS: Ten patients with 'non-lesional' TLE and 10 control subjects were studied. Quantification of the relative cerebral blood flow (rCBF) and apparent diffusion coefficient (ADC) was performed for the hippocampal regions. The ratios of the ipsilateral-to-contralateral side (to the EEG lateralization) were compared with the side-to-side ratios in the controls. RESULTS: Six patients (60%) had an ADC ratio outside the control range (the larger ADC ipsilateral to the EEG lateralization in all cases). The CBF ratios were outside the control range in all eight patients (100%) in whom CEPI was performed (the lower value ipsilateral to the EEG lateralization in all cases). The magnitude of the hippocampal volume (HV) ratios showed no significant correlation with the magnitude of the ADC ratios (R=-0.03, p=0.93) or CBF ratios (R=0.36, p=0.39). There was a closer relationship with the T2 relaxometry ratios, but this was also not significant (R=-0.40, p=0.32; R=0.58, p=0.08). CONCLUSIONS: DWI and CEPI show potential as reliable tools for the lateralization of non-lesional TLE. Further studies with larger numbers are necessary to determine whether these techniques provide independent data to established MR quantitative measures.

Hemodynamic disturbances associated with endovascular embolization in newborn infants with vein of Galen malformation.

OBJECTIVE: To examine hemodynamic changes following endovascular embolization in newborn infants with vein of Galen malformation and severe cardiac failure in the first week of life. STUDY DESIGN: Over a recent 5-year period, nine such infants were identified. In seven of these infants, changes in arterial blood pressure were analyzed in relation to the timing of embolization procedures. RESULTS: A significant increase in arterial blood pressure was noted after most embolizations. In two infants, this systemic hypertension was severe and treated using intravenous antihypertensive drugs. Both infants subsequently developed complete infarction of both cerebral hemispheres with sparing of the brainstem and cerebellum. Mortality in the nine infants was 33%, and 83% of the survivors were neurologically normal or near normal at follow-up. CONCLUSION: The systemic hypertension observed following endovascular embolizations may provide a protective mechanism to maintain cerebral blood flow after reperfusion injury. Lowering blood pressure in this situation may therefore be detrimental.

Refining the perfusion-diffusion mismatch hypothesis.

BACKGROUND AND PURPOSE: The Echoplanar Imaging Thrombolysis Evaluation Trial (EPITHET) tests the hypothesis that perfusion-weighted imaging (PWI)-diffusion-weighted imaging (DWI) mismatch predicts the response to thrombolysis. There is no accepted standardized definition of PWI-DWI mismatch. We compared common mismatch definitions in the initial 40 EPITHET patients. METHODS: Raw perfusion images were used to generate maps of time to peak (TTP), mean transit time (MTT), time to peak of the impulse response (Tmax) and first moment transit time (FMT). DWI, apparent diffusion coefficient (ADC), and PWI volumes were measured with planimetric and thresholding techniques. Correlations between mismatch volume (PWIvol-DWIvol) and DWI expansion (T2(Day 90-vol)-DWI(Acute-vol)) were also assessed. RESULTS: Mean age was 68+/-11, time to MRI 4.5+/-0.7 hours, and median National Institutes of Health Stroke Scale (NIHSS) score 11 (range 4 to 23). Tmax and MTT hypoperfusion volumes were significantly lower than those calculated with TTP and FMT maps (P<0.001). Mismatch > or =20% was observed in 89% (Tmax) to 92% (TTP/FMT/MTT) of patients. Application of a +4s (relative to the contralateral hemisphere) PWI threshold reduced the frequency of positive mismatch volumes (TTP 73%/FMT 68%/Tmax 54%/MTT 43%). Mismatch was not significantly different when assessed with ADC maps. Mismatch volume, calculated with all parameters and thresholds, was not significantly correlated with DWI expansion. In contrast, reperfusion was correlated inversely with infarct growth (R=-0.51; P=0.009). CONCLUSIONS: Deconvolution and application of PWI thresholds provide more conservative estimates of tissue at risk and decrease the frequency of mismatch accordingly. The precise definition may not be critical; however, because reperfusion alters tissue fate irrespective of mismatch.

A combined case of macroprolactinoma, growth hormone excess and Graves' disease.

Thyrotoxicosis due to Graves disease is a relatively common endocrine disorder. The occurrence of a prolactinoma with co-secretion of growth hormone (GH) is on the other hand, rare. We report the rare co-existence of Graves' disease in a patient with macroprolactinoma and GH hypersecretion and describe the successful response to medical therapy with dopamine agonist and antithyroid therapy. We hypothesize that hyperprolactinaemia played a role in promoting autoimmune thyroid disease in our patient and that treatment of hyperprolactinaemia may have been important in suppressing autoimmune disease activity in Graves' disease. This case also reflects on the close and complex interactions between thyroid hormones, prolactin (PRL), GH and testosterone (T).

Perfusion thresholds in acute stroke thrombolysis.

BACKGROUND AND PURPOSE: Perfusion-weighted MRI has been shown to be useful in the early identification of cerebral tissue at risk of infarction during acute ischemia. Identification of threshold perfusion measures that predict infarction may assist in the selection of patients for thrombolysis. METHODS: Mean transit time (MTT), regional cerebral blood flow (rCBF), and regional cerebral blood volume (rCBV) maps were generated in 35 acute stroke patients (17 treated with tissue plasminogen activator and 18 control patients) imaged within 6 hours from symptom onset. Day 90 outcome infarcts (T2-weighted MRI) were superimposed on acute MTT, rCBF, and rCBV maps. Perfusion-weighted MRI measures were then calculated for 2 regions: infarcted and salvaged tissue. RESULTS: MTT was prolonged by 22% in infarcted regions relative to salvaged tissue (P<0.001). rCBF was 10% lower in infarcted tissue than in salvaged regions (P<0.01). rCBV did not differ significantly between infarcted and salvaged regions. When reperfusion occurred, tissue with more severely prolonged MTT was salvaged from infarction relative to patients with persistent hypoperfusion (P<0.05). In contrast, rCBF in salvaged regions did not differ between patients with and without reperfusion. In reperfused patients, an inverse correlation (R=0.93, P<0.001) was found between time of initial MRI scan and MTT delay in salvaged tissue. CONCLUSIONS: Both increases in MTT and decreases in rCBF predict infarction. Differences in MTT also predict salvage in more severely hypoperfused tissue after reperfusion, suggesting that it is the most clinically useful quantitative perfusion measure. Perfusion thresholds for infarction need to be assessed in the context of symptom duration.

Perfusion magnetic resonance imaging maps in hyperacute stroke: relative cerebral blood flow most accurately identifies tissue destined to infarct.

BACKGROUND AND PURPOSE: In ischemic stroke, perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) provide important pathophysiological information. A PWI>DWI mismatch pattern suggests the presence of salvageable tissue. However, improved methods for distinguishing PWI>DWI mismatch tissue that is critically hypoperfused from benign oligemia are required. METHODS: We investigated the usefulness of maps of relative cerebral blood flow (rCBF), volume (rCBV), and mean transit time (rMTT) to predict transition to infarction in hyperacute (<6 hours) stroke patients with PWI>DWI mismatch patterns. Semiquantitative color-thresholded analysis was used to measure hypoperfusion volumes, including increasing color signal intensity thresholds of rMTT delay, which were compared with infarct expansion, outcome infarct size, and clinical status. RESULTS: Acute rCBF lesion volume had the strongest correlation with final infarct size (r=0.91, P<0.001) and clinical outcome (r=0.67, P<0.01). There was a trend for acute rCBF>DWI mismatch volume to overestimate infarct expansion between the acute and outcome study (P=0.06). Infarct expansion was underestimated by acute rCBV>DWI mismatch (P<0.001). When rMTT lesions included tissue with moderately prolonged transit times (mean delay 4.3 seconds, signal intensity values 50% to 70%), infarct expansion was overestimated. In contrast, when rMTT lesions were restricted to more severely prolonged transit times (mean delay 6.1 seconds, signal intensity >70%), these regions progressed to infarction in all except 1 patient, but infarct expansion was underestimated (P<0.001). CONCLUSIONS: The acute rCBF lesion most accurately identified tissue in the PWI>DWI mismatch region at risk of infarction. Color-thresholded PWI maps show potential for use in an acute clinical setting to prospectively predict tissue outcome.

Computed tomographic study of children with classic autism.

Computed tomographic (CT) scans were obtained for nine autistic boys aged between 9 and 16 years. All were considered to have classic childhood autism of unequivocal diagnosis, with symptoms present from infancy, and were functioning in the borderline or normal level of intelligence. They had performed poorly on tests purported to measure left hemispheric functions. There was no sign of abnormality of any kind on the CT scans or any asymmetry that might be related to lateralized cognitive functions. It is suggested that earlier reported abnormalities are a function of the inclusion of patients with a heterogeneous collection of disorders in the tested sample.

Prediction of functional outcome and tissue loss in acute cortical infarction.

OBJECTIVE: To compare the acute Allen's Prognostic Score, Canadian Neurological Score, and subacute Barthel Index as predictors of outcome functional status and infarct size at 3 months in patients with acute cortical infarction. DESIGN: A prospective study of acute stroke predictors and outcome measurements in a cohort of sequential hospitalized patients. PATIENTS: Fifty-one patients with acute cortical infarction and without previous disability assessed 24 hours after onset with Allen's Prognostic Score and the Canadian Neurological Score and at 7 days with the Barthel Index. MAIN OUTCOME MEASURES: Mortality, Barthel Index, and volumetric measurement of infarct size on computed tomography 3 months after stroke. RESULTS: There were seven deaths. The outcome Barthel Index was measured in all 44 survivors, of whom 29 had computed tomography at the time outcome was determined. In a multivariate analysis, functional outcome was best predicted by Allen's Prognostic Score, a score of less than -15 having a sensitivity of 82% and specificity of 97% in predicting a poor outcome (Barthel Index, < or = 12 or death). Volumetric tissue loss was predicted only by Allen's Prognostic Score (r = .62, P < .001). CONCLUSIONS: Allen's Prognostic Score is a robust predictor of both functional outcome and tissue loss in acute cortical infarction and has a potentially important role in the analysis of the results of acute stroke intervention trials.

Epileptic seizures in acute stroke.

We evaluated prospectively the incidence of early seizures in 1000 consecutive patients with stroke and transient ischemic attacks to determine whether seizure occurrence correlates with stroke type, pathogenesis, or outcome. Seizures occurred in 44 patients (4.4%; SE, 0.7%), including 10 (15.4%) of 65 (SE, 4.5%) with lobar or extensive hemorrhage, 6 (8.5%) of 71 (SE, 3.3%) with subarachnoid hemorrhage, 24 (6.5%) of 370 (SE, 1.3%) with cortical infarction, and 4 (3.7%) of 109 (SE, 1.8%) with hemispheric transient ischemic attacks. Lacunar infarcts and deep hemorrhages were not associated with seizures. Arteriovenous malformation was a common cause of lobar hemorrhage with early seizures, but in cortical infarcts there was no association between seizure occurrence and pathogenesis. Seizures generally occurred within 48 hours of stroke onset, were usually single, partial, and readily controlled. Seizures were not associated with a higher mortality or worse functional outcome.

A prospective study of lacunar infarction using computerized tomography.

Sequential computed tomography (CT) scans were performed for up to 7 months on patients who presented with clinical evidence of lacunar infarction or ischemia. Sixty-nine percent of the patients showed lacunar infarction, and a negative scan did not suggest a better prognosis in stroke patients. Of patients with transient ischemic attacks (TIA) (lacunar), those with repeated bursts of hemiplegia (capsular warning syndrome) were more likely to be CT-positive (p less than 0.01). The clinical features of patients with lacunar infarction were examined and correlated with the features of infarction. Partial syndromes were found in 32% of the cases and included examples of monoparesis and dysarthria alone.

Cerebral venography and manometry in idiopathic intracranial hypertension.

Cerebral venography and manometry in nine patients with idiopathic intracranial hypertension consistently showed venous hypertension in the superior sagittal sinus and proximal transverse sinuses, with a significant drop in venous pressure at the level of the lateral third of the transverse sinus. The abnormality, clearly demonstrated by manometry, was not well shown on the venous phase of cerebral angiography. The appearance of the transverse sinus on venography varied from smooth tapered narrowing to discrete intraluminal filling defects that resembled mural thrombi. Two patients with intracranial hypertension due to minocycline did not show venous hypertension.

Epilepsy in the nevoid basal-cell carcinoma syndrome (Gorlin syndrome): report of a case due to a focal neuronal heterotopia.

We present a case of uncontrolled temporal lobe epilepsy due to a focal left temporal neuronal heterotopia associated with the nevoid-basal-cell carcinoma syndrome. This is the first pathologically described lesion associated with temporal lobe epilepsy in this syndrome. Because the patient's seizures resolved after a modified left anterior temporal lobectomy, this case illustrates that epilepsy in patients with the nevoid basal-cell carcinoma syndrome is potentially curable and should be investigated appropriately.

Manometry combined with cervical puncture in idiopathic intracranial hypertension.

OBJECTIVE: To determine by cerebral venography and manometry in patients with idiopathic intracranial hypertension the cause of the previously demonstrated venous hypertension in the superior sagittal and proximal transverse sinuses. METHODS: Cerebral venous sinus pressure was measured before and immediately after C1-2 puncture with removal of 20 to 25 mL of CSF. RESULTS: Lowering the intracranial pressure by lateral C1-2 puncture during manometry has shown that the venous hypertension resolves immediately. CONCLUSION: These studies indicate that the venous hypertension is due to compression of the transverse sinuses by raised intracranial pressure and not due to a primary obstructive process in the cerebral venous sinuses.

Prediction of stroke outcome with echoplanar perfusion- and diffusion-weighted MRI.

OBJECTIVES: We examined the utility of echoplanar magnetic resonance perfusion imaging and diffusion-weighted imaging (DWI) in predicting stroke evolution and outcome in 18 patients with acute hemispheric infarction. METHODS: Patients were studied within 24 hours (mean, 12.2 hours), subacutely (mean, 4.7 days), and at outcome (mean, 84 days). Comparisons were made between infarction volumes as measured on perfusion imaging (PI) and isotropic DWI maps, clinical assessment scales (Canadian Neurological Scale, Barthel Index, and Rankin Scale), and final infarct volume (T2-weighted MRI). RESULTS: Acute PI lesion volumes correlated with acute neurologic state, clinical outcome, and final infarct volume. Acute DWI lesions correlated less robustly with acute neurologic state, but correlated well with clinical outcome and final infarct volume. Three of six possible patterns of abnormalities were seen: PI lesion larger than DWI lesion (65%), PI lesion smaller than DWI lesion (12%), and DWI lesion but no PI lesion (23%). A pattern of a PI lesion larger than the DWI lesion predicted DWI expansion into surrounding hypoperfused tissue (p < 0.05). In the other two patterns, DWI lesions did not enlarge, suggesting that no significant increase in ischemic lesion size occurs in the absence of a larger perfusion deficit. CONCLUSIONS: Combined early PI and DWI can define different acute infarct patterns, which may allow the selection of rational therapeutic strategies based on the presence or absence of potentially salvageable ischemic tissue.

Absent middle cerebral artery flow predicts the presence and evolution of the ischemic penumbra.

OBJECTIVES: In acute ischemic stroke the pattern of a perfusion-imaging (PI) lesion larger than the diffusion-weighted imaging (DWI) lesion may be a marker of the ischemic penumbra. We hypothesized that acute middle cerebral artery (MCA) occlusion would predict the presence of presumed "penumbral" patterns (PI > DWI), ischemic core evolution, and stroke outcome. METHODS: Echoplanar PI, DWI, and magnetic resonance angiography (MRA) were performed in 26 patients with MCA territory stroke. Imaging and clinical studies (Canadian Neurological Scale, Barthel Index, and Rankin Scale) were performed within 24 hours of onset and repeated at days 4 and 90. RESULTS: MCA flow was absent in 9 of 26 patients. This was associated with larger acute PI and DWI lesions, greater PI/DWI mismatch, early DWI lesion expansion, larger final infarct size, worse clinical outcome (p < 0.01) and provided independent prognostic information (multiple linear regression analysis, p < 0.05). Acute penumbral patterns were present in 14 of 26 patients. Most of these patients (9 of 14) had no MCA flow, whereas all nonpenumbral patients (PI < or = DWI lesion) had MCA flow (p < 0.001). Penumbral-pattern patients with absent MCA flow had greater DWI lesion expansion (p < 0.05) and worse clinical outcome (Rankin Scale score, p < 0.05). CONCLUSIONS: Absent MCA flow on MRA predicts the presence of a presumed penumbral pattern on acute PI and DWI and worse stroke outcome. Combined MRA, PI, and DWI can identify individual patients at risk of ischemic core progression and the potential to respond to thrombolytic therapy beyond 3 hours.

Hippocampal sclerosis can be reliably detected by magnetic resonance imaging.

Two independent blinded observers reported the preoperative MRIs in a series of 81 consecutive patients with intractable temporal lobe epilepsy who were undergoing temporal lobectomy. We then compared the nature and lateralization of the MRI abnormalities with the pathologic diagnosis and the side of lobectomy. The MRI criteria of hippocampal sclerosis were an increased T2-weighted signal and the signal's confinement to a unilaterally small hippocampus. Imaging was performed in coronal and axial planes, specially orientated along and perpendicular to the long axis of the hippocampal body. We found diagnostic MRI abnormalities in 25 of the 27 cases with pathologically proven hippocampal sclerosis (sensitivity 93%, specificity 86%). In addition, we detected all 13 foreign tissue lesions on MRI. Overall, we detected lateralized lesions on MRI that correctly predicted the side of the epileptogenic temporal lobe in 72 cases (89%), with 2 possible errors. A learning effect in appreciating the relatively subtle MRI changes of hippocampal sclerosis was apparent in our later cases, as shown by an improved correlation between the 2 observers. This study demonstrates that hippocampal sclerosis can be identified on MRI with a high degree of sensitivity and specificity.

Combined (1)H MR spectroscopy and diffusion-weighted MRI improves the prediction of stroke outcome.

BACKGROUND: The prognostic value of the biochemical changes seen with proton MR spectroscopy (1H MRS) in ischemic stroke was examined. Acute diffusion-weighted imaging (DWI) was used to identify regions of ischemia for 1H MRS voxel localization. METHODS: Nineteen patients had 36 1H MRS studies, 13 patients acutely (mean, 11.1 hours), 10 subacutely (mean, 3.9 days), and 13 at outcome (mean, 82 days). Single-voxel, long-echo, timepoint-resolved spectroscopy was used to obtain lactate, n-acetylaspartate (NAA), choline, and creatine levels from the infarct core. Outcome measures were final infarct volume and clinical assessment scales (Canadian Neurological Scale, Barthel Index, and Rankin Scale). RESULTS: Acute lactate/choline ratio correlated more strongly with clinical outcome scores (r = 0.76 to 0.83; p < 0.01) and final infarct size (r = 0. 96; p < 0.01) than acute DWI lesion volume or acute NAA/choline ratio. Combination of acute lactate/choline ratio with acute DWI lesion volume improved prediction of all outcome scores (R2 = 0.80 to 0.90). The predictive effect of acute lactate/choline ratio was independent of acute DWI lesion volume (p < 0.001). In subacute and chronic infarction, both lactate/choline and NAA/choline ratios continued to correlate with outcome (p < 0.05). At the chronic stage, persistent lactate/choline ratio elevation strongly correlated with outcome measures (r = 0.71 to 0.87). CONCLUSION: Lactate/choline ratio measured in the acute infarct core by 1H MRS improves the prediction of stroke outcome and provides prognostic information complementary to DWI. Lactate/choline ratio could be used as an additional marker to select patients for acute and chronic therapies.

Iodine-induced hyperthyroidism due to nonionic contrast radiography in the elderly.

PURPOSE: To identify the number of cases of hyperthyroidism that followed the performance of contrast radiography in elderly patients at a geriatric hospital in a non-iodine-deficient area and to determine the clinical course of the condition. PATIENTS AND METHODS: All patients over a 20-month period with biochemical hyperthyroidism (plasma free thyroxine level greater than 25.0 pmol/L and thyroid-stimulating hormone level less than 0.10 IU/L) were identified. Clinical features of hyperthyroidism and exposure to nonionic contrast media radiographs within the previous 12 months were sought. Follow-up extended from 6 to 22 months. RESULTS: A total of 28 patients with hyperthyroidism (aged 70 to 96 years) were identified. Seven patients (25%) had documented biochemical development of hyperthyroidism (five) or subsequent hyperthyroidism (two) 3 to 8 weeks after nonionic contrast media radiography. The four patients who underwent scanning had a multinodular thyroid, and thyroid antibodies were not detected in five of five patients. Although the condition appeared self-limited and six of six patients were euthyroid after 18 months, the condition was not benign; progress and recovery were adversely affected by hyperthyroidism. Four patients had a good response to treatment with an antithyroid drug (carbimazole). CONCLUSION: Iodine-induced thyrotoxicosis following contrast radiography was found in 7 of 28 cases of hyperthyroidism seen at a geriatric hospital. Although the condition appears ultimately self-limited, pharmacologic control of severe clinical features may be required. The frequency of this condition in a non-iodine-deficient area appears related to the more common occurrence of autonomous thyroid nodules in the elderly. Because performance of contrast radiography is more common in this age group, the recognition and treatment of iodine-induced thyrotoxicosis are of increasing clinical importance.

Dynamic gadolinium DTPA-enhanced magnetic resonance of intravascular stents.

RATIONALE AND OBJECTIVES: Magnetic resonance contrast enhancement depends on the timing of image acquisition. Human trials have demonstrated efficacy of renal artery stents on salvage of renal function. This study assessed the ability of dynamic gadolinium (Gd)-DTPA administration to demonstrate renal and iliac artery stent patency compared to conventional angiography as the gold standard. METHODS: Seven subjects with eight stents referred for angiography underwent dynamic magnetic resonance studies, all with renal artery stenting. All were examined with conventional angiography and after dynamic Gd-DTPA infusion. Coronal magnetic resonance images were acquired using a GE Signa 1.5 T magnet (fast spoiled gradient echo; echo time = 4.2 ms; repetition time = 68-150 ms; flip angle = 75 degrees) 0 to 600 seconds after 0.1 mmol/Kg Gd-DTPA intravenous bolus injection during sequential breath-hold acquisitions 13 to 32 seconds each. RESULTS: All eight stents were visualized with 100% accurate patency documentation. CONCLUSIONS: Fast spoiled gradient echo magnetic resonance imaging with bolus Gd-DTPA administration can provide adequate time and spatial resolution to demonstrate arterial stent patency.

Analysis of dynamic computed tomography scan brain images.

Dynamic computed tomography (DCT) of the brain can be used to study the transit time of first passage of a bolus injection of intravenous contrast medium. Comparison of cerebral perfusion with corresponding sites in the left and right cerebral hemispheres is of diagnostic interest because a real difference may be indicative of differential damage. A method for estimating the mean transit time and approximating its standard error, by assuming a gamma function for the response curve and an appropriate error structure, is presented. Expressed as log-linear regression, estimation is achieved by maximum likelihood using a statistical package such as GLIM or SPSSX. Statistical comparison of the mean transit time to or between corresponding sites can be made; issues of model fit and biologic interpretation need to be considered as an integral part of statistical inference. These methods enable users of CT equipment (without specific software for estimation of mean transit time) to use any log-linear routine for diagnostic purposes. An example of the fit procedure and interpretation in the light of clinical evidence is given.