Cerebral abnormalities in myotonic dystrophy. Cerebral blood flow, magnetic resonance imaging, and neuropsychological tests.

OBJECTIVE: To study cerebral abnormalities in myotonic dystrophy (MD) and determine the different patterns of cerebral function in patients with MD with maternal (mMD) vs paternal (pMD) inheritance. DESIGN: Patients with MD and normal controls were studied with neuropsychological testing, magnetic resonance imaging, and single photon emission computed tomography. SETTING: Studies were done at Harbor-UCLA Medical Center, Torrance, Calif. PATIENTS AND OTHER PARTICIPANTS: Twenty-two consecutive-patients with MD, 11 of whom had pMD and eight mMD, and 10 normal controls were studied. Diagnoses were made on the basis of family history, electromyography, and clinical examinations. Normal subjects in the same age distribution were studied for comparisons. RESULTS: We found significantly lower neuropsychological performance and cerebral blood flow in the patients with MD compared with the controls. Patients with mMD had statistically lower scores on IQ tests and more extensive cerebral hypoperfusion when compared with those with pMD. Changes in cerebral blood flow were most severe in the frontal and temporoparietal association cortex. Cerebral blood blow measures strongly correlated with IQ. CONCLUSIONS: Patients with mMD had earlier onset of disease and lower IQs than the pMD group. The pattern of cerebral perfusion in the mMD group was consistent with a diffuse brain injury, while cerebral perfusion in pMD showed more minor changes. These findings emphasize the cognitive differences between mMD and pMD.

Nonconvulsive status epilepticus of frontal origin.

OBJECTIVES: To determine the electroclinical characteristics and causative factors of nonconvulsive status epilepticus (NCSE) of frontal origin. METHODS: The authors conducted a 5-year prospective study. RESULTS: Ten patients were studied (seven men, three women; mean age, 56.4 years). Six patients did not have previous epilepsy. The mean diagnostic delay was 48 hours (range, 3 to 96 hours). Two types of frontal NCSE were identified. In type 1 (n = 7), mood disturbances with affective disinhibition or affective indifference were associated with subtle impairment of cognitive functions without overt confusion. EEG showed a unilateral frontal ictal pattern and normal background activity. In type 2 (n = 3), impaired consciousness was associated with bilateral, asymmetric frontal EEG discharges occurring on an abnormal background. Ictal and postictal 99mTc hexamethyl propylene amine oxime (HMPAO) SPECT was performed in five patients and showed unilateral or bilateral frontal HMPAO uptake that aided localization, especially in type 2 NCSE of frontal origin. Etiologies included a focal frontal lesion in six patients (three of which were tumors), neurosyphilis, and nonketotic hyperglycemia. Eight patients did not respond to initial IV benzodiazepine (BZ), but IV phenytoin controlled six patients successfully. The immediate outcome was favorable in all patients. There was no long-term recurrence of SE in seven patients. CONCLUSIONS: NCSE of frontal origin is a heterogeneous syndrome. Some cases are best described as simple partial NCSE, others as complex partial SE, and there are forms that overlap with absence SE. Emergency EEG and neuropsychological assessment are diagnostic, and SPECT may be useful. Many patients may not respond to IV BZ.

Acute cardiac effects of mediastinal irradiation: assessment by radionuclide angiography.

Mediastinal irradiation is considered as a long term cardiac risk factor, although no myocardial dysfunction can usually be documented during long term follow-up of the patients having undergone this treatment. We prospectively studied on 124 patients the early effects of irradiation on the myocardium using radionuclide angiography Left ventricular ejection fraction was measured at three different times: before starting the irradiation, 15 days after and more than 2 months after the end of treatment. The patients were divided into four groups according to the type of irradiation received: M group of 53 patients (mediasteinal irradiation), L group of 33 patients (left mammary chain irradiation), R group of 25 patients (right mammary chain irradiation), C group for 13 control patients (irradiation field did not include the heart). Sixty-nine of these patients were treated by chemotherapy, including adriamycin in 48 of them. For all patients for whom the myocardium was included into the field of irradiation (M, L, and R) there is a significant fall of the Left ventricular ejection fraction 15 days after the end of treatment, with recovery after 2 months. This fall is not seen in controls. Patients who received adriamycin follow the same evolution, and there is no significant difference in the basal LVEF value nor in the magnitude of the fall.

Impact of attenuation correction by simultaneous emission/transmission tomography on visual assessment of 201Tl myocardial perfusion images.

UNLABELLED: It has been shown in clinical studies that for subjects with a low likelihood of coronary artery disease (CAD), attenuation correction (AC) improves the specificity of defect detection in the inferior wall (right coronary artery [RCA] region). The aim of this study was to investigate the effect of AC on the visual interpretation of the RCA and anteroseptal (corresponding to the left anterior descending artery [LAD]) regions in CAD patients. METHODS: Fifty-six patients with suspected CAD underwent 20Tl stress/4 h-delayed imaging SPECT using a simultaneous 201Tl emission/99mTc transmission imaging protocol. Images were reconstructed using the maximum likelihood-expectation maximum algorithm without and with AC. The stress/4 h-delayed images were interpreted blindly for reversible or fixed defects in the RCA and LAD regions by three experienced physicians. Coronary angiography, electrocardiography and enzyme findings were used to establish diagnoses of ischemia or infarction, and receiver operating characteristic (ROC) analyses were performed. RESULTS: Statistical testing of ROC curve areas showed that defect detection performance improved with AC when compared with performance without AC in the RCA region. This was mainly the result of a systematic increase in specificity of 12% or more (for any observer and any type of defect) for a similar sensitivity (no definite change in sensitivity values). However, defect detection performance significantly decreased in the LAD territory with AC images (P < 0.05) because of a systematic decrease in sensitivity of 20% or more, with no consistent change in specificity. Similar trends were observed when reversible and fixed defects were considered separately. CONCLUSION: AC significantly affects the visual interpretation of 201Tl stress/4 h-delayed SPECT images. This study confirmed the increase in specificity obtained with AC in the RCA territory. However, in the population considered, the studied AC was deleterious for the LAD territory assessment.

Major upward creep of the heart during exercise thallium-201 myocardial SPECT in a patient with chronic obstructive pulmonary disease.

We report on a patient in whom we observed an unusually important upward creep of the heart on postexercise 201TI tomographic acquisition. When uncorrected, this led to reconstruction of grossly abnormal tomograms, which were normal after correction of upward creep of the heart. This phenomenon may be related to the patient's history of chronic obstructive pulmonary disease. Special attention should be given to upward creep artifact in such pulmonary diseases.

Usefulness of endocoronary electrocardiogram in the detection of myocardial viability and comparison with single-photon emission computed tomography Tl-201.

In 20 patients who had recently had an acute myocardial infarction, we compared endocoronary electrocardiographic modifications recorded during angioplasty with thallium-201 for the detection of myocardial viability. Our data demonstrate that endocoronary electrocardiography can be an easy and reliable tool to assess viability, with sensitivity, specificity, and positive and negative predictive values of 100%, 80%, 94%, 100%, respectively.

A radiolabelled iodobenzamide for malignant melanoma staging.

123I-N-(di-ethylamino-2-ethyl) 4 iodobenzamide (I-BZA) has been put forward by the Clermont-Ferrand INSERM U71 group (France) as a tracer for malignant melanoma. We report on the clinical results obtained in 56 studies performed on 48 patients. Whole body scans along with spot views were obtained after injection of 185 MBq of I-BZA. The scans were read by three independent observers and correlated to the clinical findings and the other imaging modalities available, taking into account all lesions larger than 1 cm. Patients were classified into two groups on the basis of a post-treatment survey of patients: group I, in complete remission (24 scans); group II: documented metastases (32 scans). In group 1, 21 studies were truly negative. However, three studies showed positive results. Only one turned out to be a false positive (specificity 95%), the other two revealed unknown lesions and modified the patients' management. In group II, 73% of the known metastases were detected with higher sensitivities (> 80%) for eye and orbit, lung and abdomen. One false positive was reported and four new lesions were detected. I-BZA scintigraphy has the same sensitivity as immunoscintigraphy with higher specificity and without the risk of xenoimmunization. It is a useful tool for staging malignant melanoma which can improve patient management.

Ventricular patch endocarditis caused by Propionibacterium acnes: advantages of gallium scanning.

Propionibacterium acnes is a weakly pathogenic commensal of the skin. When isolated from blood cultures it is often considered a contaminant. However, P. acnes may be responsible for severe infections and its role in certain cases of infectious endocarditis has now been definitely established.(1) We report a case of endocarditis due to P. acnes stemming from a ventricular patch and revealed by a gallium 67 scan.

A single photon emission computed tomography study of cerebral regional perfusion changes induced by a learning task in subjects with mild memory impairment.

Fifteen nondemented subjects with memory complaints underwent serial single photon emission computed tomography (SPECT) studies with technetium-99m-d, l-hexamethyl-propylene amine oxime (HMPAO) as tracer. Scans were carried out under a baseline conditions and during the learning phase of the Memory Efficiency Profile (MEP), a combined visual perception and memory task developed by Rey. Results indicate a positive correlation between activation, as indexed by HMPAO uptake, and neuropsychological assessment. Right temporal activation was correlated with MEP immediate recall. The right cerebellum was correlated with both MEP immediate and delayed recall. This study suggests that SPECT can show cortical activation during cognitive performance in subjects with mild memory impairment.

Assessment of cerebral perfusion using quantitative EEG cordance.

Brain electrical activity is related to cerebral perfusion. The nature of this relationship is unclear, however, and surface-recorded activity has not been a reliable indicator of brain perfusion. We studied 27 subjects, all of whom were examined with single photon emission tomography (SPECT) and quantitative electroencephalography (QEEG), to assess associations between QEEG cordance and relative brain perfusion. Cordance has two indicator states: concordance, which may indicate high perfusion; and discordance, which may indicate low perfusion. We used multiple linear regression to assess the association between cordance and SPECT values, and found that cordance values were strongly associated with tissue perfusion. Concordance in the alpha band was associated both with mean tissue perfusion and the volume of normally perfused tissue, and it had a stronger association with perfusion than any other QEEG variable. Discordance in the beta 1 band was associated with mean perfusion, and it had a stronger association than did relative but not absolute power. These data suggest that cordance may be useful for the noninvasive assessment of brain perfusion.

Computerized localization of brain structures in single photon emission computed tomography using a proportional anatomical stereotactic atlas.

An accurate identification of cerebral structures is necessary to perform quantification of single photon emission computed tomography (SPECT). We have developed an anatomical localization system that accounts for individual brain shapes and sizes by using the Talairach proportional grid system. The locations of the commissural lines, which define the stereotactic coordinate system, are calculated from the external landmarks provided by the canthomeatal line. This is validated on MRI images. When applied to SPECT data, the use of a neuroanatomical atlas data along with the automaticity of the processing guarantees a high degree of objectivity and inter-observer reproducibility.

Single photon emission computed tomography study of subclinical rhythmic electrographic discharge in adults.

Subclinical rhythmic electrographic discharge in adults (SREDA) is considered a benign EEG pattern of uncertain significance, although it may closely resemble an EEG seizure pattern. We investigated a 57-year-old man with a very lateralized epileptiform activity localized to the occipito-temporal areas of the right hemisphere. Neuropsychological tests, clonazepam injection and 99m Tc-HMPAO-SPECT were performed during the SREDA and compared to the interparoxysmal data, providing further evidence that SREDA cannot be considered as an epileptic pattern and that, in some instances, it may be related to chronic hypoxic/ischemic mechanisms.

Effect of pacing rate on regional left ventricular wall motion. Assessment by quantitative analysis of equilibrium radionuclide angiography.

We evaluated the hemodynamic impact of right ventricular pacing at different stimulation frequencies. Fourteen patients with a right ventricular pacemaker (VVI pacing with retrograde P wave) but without clinical and electrocardiographic evidence of coronary artery disease underwent two equilibrium radionuclide angiographies: one under low heart rate (50/60 beats per minute) and the other under fast heart rate (90/100 beats per minute). Left ventricular global and sectorial ejection fractions, amplitude and phase images of first harmonic, and sectorial phases of left ventricle were analyzed. In twelve patients (84.7%), sectorial ejection fraction abnormalities in the left ventricular apicoseptal and inferoapical regions were observed under low heart rate, and worsened under fast heart rate, while new onset sectorial ejection fraction abnormalities under fast heart rate were observed in the other two patients with normal sectorial ejection fraction under low heart rate. Sectorial ejection fractions of left ventricular apicoseptal and inferoapical regions significantly changed between low and high heart rate (- 14.1 +/- 3.8%, p < 0.005; - 7.5 +/- 2.4%, p < 0.01 respectively). Left ventricular sectorial phases were abnormal in only two patients (14.3%) under low heart rate, and in twelve patients (84.7%) under fast heart rate. Our study confirms that left ventricular regional wall motion abnormalities during VVI pacing significantly worsen under fast heart rate in comparison to those under low heart rate.

Perfusion brain SPECT and statistical parametric mapping analysis indicate that apathy is a cingulate syndrome: a study in Alzheimer's disease and nondemented patients.

Apathy is the most frequent behavioral symptom in Alzheimer's disease and is also frequently reported in other brain organic disorders occurring in the elderly. Based on the literature, we hypothesized that apathy was related to an anterior cingulate hypofunction. Forty-one subjects were studied. According to ICD 10 diagnostic criteria, 28 patients had Alzheimer dementia (demented: diagnostic group 1), and 13 had organic personality disorders or mild cognitive impairment not attributable to dementia (nondemented: diagnostic group 2). Apathy was evaluated by the Neuro-Psychiatric Inventory. As a result each diagnostic group was divided into two symptomatic subgroups: apathetic or nonapathetic. Brain perfusion was measured by (99m)Tc-labeled bicisate (ECD) brain SPECT and the images were compared using Statistical Parametric Mapping (SPM96). We began by comparing apathetic vs nonapathetic patients, whatever their diagnostic group (whole population), then analyzed them within each group. Twenty-one subjects were apathetic (14 in group 1 and 7 in group 2) and 20 were not (14 in group 1 and 6 in group 2). For the whole population, the Z map showed a significant decrease in ECD uptake for the apathetic patients in the anterior cingulate (P < 0.002) bilaterally. This area was also identified as hypoactive by SPM analysis in the demented (P < 0.035) and in the nondemented (P < 0.02) apathetic patient groups. Finally, conjunction analysis indicated that the anterior cingulate was the common hypoactive structure of the two apathetic subgroups (Z = 4.35, P < 0.0009). These results point to a close relationship between apathy and the anterior cingulate region.

Behavioral and psychological symptoms in Alzheimer's disease. Relation between apathy and regional cerebral perfusion.

Fundamental and therapeutic research in Alzheimer's disease (AD) focused for a long time exclusively on cognitive aspects. However, AD also frequently involves complex disorders of affect and behavior, which are currently grouped under the heading 'behavioral and psychological signs and symptoms of dementia' (BPSSD). Several rating tools have been developed over the years on the basis of a variety of source data. Some are derived from psychiatric practise or have specifically been developed for dementia, such as the Neuropsychiatric Inventory (NPI). In this study we prospectively used the NPI to examine BPSSD. Sixty-three French patients (mean age 74.7 years, SD 7.9) with a Mini-Mental State Examination (MMSE) score higher than 10 were examined. BPPSD were detected by NPI in 95. 2% of the patients. Anxiety was the most common abnormality (65.1%), followed by apathy and dysphoria (58.7%). The highest frequency x severity NPI score was observed for apathy. In order to identify the relationship between regional cerebral perfusion and apathy, 20 of these AD patients underwent a technetium-99m-bicisate SPECT protocol within the same week as the NPI evaluation. The mean age of this population was 74.4 years (SD 5.3) and the mean MMSE score was 21 (SD 4.1). The apathy NPI score was correlated with right cingulate deficit whereas the highest correlation for the MMSE was with the left temporoparietal area. This stresses the interest to focus on SPECT imaging of AD patients not only in the posterior areas. CopyrightCopyright 1999S.KargerAG,Basel

Correlations of left ventricular diastolic parameters and heart rate: assessment through right ventricular pacing.

This study evaluated the correlations between left ventricular (LV) diastolic parameters assessed by equilibrium radionuclide angiography (ERNA) and heart rate (HR) through right ventricular pacing. Twelve patients with a permanent right ventricular apex pace-maker were included. Serial ERNA studies were performed under 6 sets of pacing cycle length (heart rate = 52, 62, 72, 82, 92, 104 beats/min) for each patient. The left ventricular ejection fraction was 49.9% +/- 3.1% under pacing HR of 52 bpm and 43.8% +/- 3.1% under pacing HR of 104 bpm. The peak filling rate (PFR) increased very significantly with HR (r = 0.98, P less than 0.001). When the relative changes of end-diastolic volume were taken into account, the correlation between PFR and HR remained significant (r = 0.94, P less than 0.001). The absolute time to PFR (TPFR) did not significantly change with HR, but the ratio of TPFR to cycle length strongly correlated with HR. Our study clearly demonstrates that the PFR assessed by ERNA increases and the TPFR occupies an increasing proportion of the cycle length as HR increases. Therefore, LV diastolic parameters should be normalized for HR in clinical applications. In particular, HR changes should be considered when LV diastolic parameters are used for the assessment of therapeutic interventions.

Early (99m)Tc-ethylcysteinate dimer brain SPECT patterns in the acute phase of stroke as predictors of neurological recovery.

OBJECTIVES: Accurate prediction of outcome in acute stroke would help in identifying subgroups of patients for therapeutic trials and intravenous thrombolysis. The purpose of this study was to prospectively test the hypothesis that brain SPECT, with (99m)Tc-L, L-ethylcysteinate dimer (ECD), a tracer sensitive to cell function, performed in the first hours after stroke onset, adds predictive power to concomitant neurological evaluation. METHODS: Twenty-four patients with a first-ever middle cerebral artery stroke were prospectively studied with ECD-SPECT within 12 h after stroke onset. Neurological evaluation was performed using Orgogozo's scale at admission and 3 months later in order to calculate the percent Martinez-Vila evolution indices (EI%). Semiquantitative visual analysis of SPECT images was performed in 6 cortical regions relevant for carotid artery territory. Both the extent and the intensity of cortical reduced ECD uptake were calculated, leading to an 'ischemia' score, corresponding to the sum of regions of interest (ROI) where ECD uptake was between 40 and 80% of the contralateral healthy hemisphere, and an 'irreversibly damaged tissue' (IDT) score, corresponding to an uptake below 40%, and a total score (ischemia + IDT). Each patient was assigned to one of three patterns: (1) pattern I with severe ECD cortical uptake reduction defined by at least one ROI with uptake under 40%, (2) pattern II with moderate ECD cortical uptake reduction (40-80%) only and (3) pattern III with normal ECD uptake. RESULTS: There were 11 patients (46%) with pattern I ECD-SPECT. This group had almost invariably (10/11 patients) a poor outcome. The 12 patients (50%) classified in pattern II had a variable clinical outcome, ranging from improvement to deterioration. The single patient with a normal SPECT (pattern III) had a full clinical recovery. Both total score and IDT score were strongly significantly correlated with neurological recovery EI% (respectively p = 0.006 and 0.004). Their predictive value was significantly higher than, and independent of, day 0 neurological evaluation. No patient had an increased ECD uptake. CONCLUSION: Our results show that the degree of ECD cortical uptake reduction, measured on early brain SPECT, is a strong predictor of neurological recovery. ECD-SPECT data have a higher predictive value than day 0 neurological evaluation. The apparently better predictive value of ECD over hexamethylpropyleneamine oxime may reflect this tracer's brain retention mechanisms which are weighted more towards cell function than towards perfusion. ECD-SPECT is easily obtainable and may help in selecting out from therapy those patients who are likely to have either very good or very poor spontaneous outcome, and thus improve the assessment of acute stroke and the choice of therapeutic strategy.