Sensorimotor gating in boys with Tourette's syndrome and ADHD: preliminary results.

Deficits in sensorimotor gating, defined by prepulse inhibition (PPI), have been associated with subcortical dopaminergic overactivity in animal and clinical studies. Utilizing supraorbital nerve electrical stimulation, we produced adequate blink responses and measured decreases in amplitude resulting from electric prestimuli just above sensory threshold. Seven boys comorbid for attention-deficit hyperactivity disorder (ADHD) and a tic disorder had significantly reduced PPI, compared to 14 screened controls and seven boys with ADHD alone. If independently replicated, these results may reflect greater neurologic immaturity in these comorbid subjects. Alternatively, these findings, together with other converging lines of evidence, suggest that deficient pallidal inhibition may be etiologically related to tic and movement disorders.

The importance of Spratling.

William P. Spratling made important contributions to American epileptology at the beginning of this century. He was the first medical superintendent of Craig Colony for Epileptics from 1893 to 1908, cofounder and president of the National Association for the Study of Epilepsy, and first editor of its scholarly journal, Transactions. During his tenure at Craig Colony, Spratling established standards for safe and humane public care of epileptics. He started the first American residency training program emphasizing epileptology. Spratling conducted the first American multicenter research on the causes of death in epilepsy. The dosage of bromide therapy, which he empirically determined, remains correct. In his book Epilepsy and Its Treatment, Spratling substantiated the cortical origin theory of epilepsy developed by Jackson and Gowers. He was the first American to postulate and investigate a biochemical etiology of generalized seizures in the absence of anatomic lesions. Despite signal accomplishments, his untimely, tragic death may explain why he remains obscure.

William P. Letchworth: philanthropist and pioneer epileptologist.

Although neither a physician nor a scientist, William Pryor Letchworth significantly improved the care and treatment of epileptics at the beginning of this century. As commissioner of the New York State Board of Charities and later president, he established Craig Colony, America's first comprehensive epilepsy facility. In Care and Treatment of Epileptics, he summarized contemporary medical and social knowledge of epilepsy. As cofounder and president of the National Association for the Study of Epilepsy, he introduced from Europe his improvements of the colony plan of construction and financed Transactions, the society's scholarly journal. He combined a sensitivity to the needs of the unfortunate with the resolve of a successful businessman. Although William Pryor Letchworth is remembered for his philanthropy and the park in western New York that bears his name, his signal contributions to modern concepts of epilepsy are unknown to most physicians. This article will acquaint readers with the life and accomplishments of this philanthropist and pioneer epileptologist.

Tremor studies in 1886 through 1889.

From biblical times to 1886, tremors were partially characterized by patterns of activation and associated disease states. William Richard Gowers and Frederick Peterson devised methods to determine the frequencies of the tremors of Parkinson's disease, alcoholism, hysteria, and other diseases. Their values concur closely with the contemporary ranges of 4.0 to 7.0 Hz in Parkinson's disease and 8.1 to 11.0 Hz in chronic alcoholism. This review properly credits these authors' pioneer investigations made with simple instruments a century ago.

John Call Dalton, Jr., MD: America's first neurophysiologist.

Before the discoveries of John Call Dalton, Jr., MD (1824-1889), innervation of laryngeal muscles, long-term effects of cerebellar lesions, and consequences of raised intracranial pressure were poorly understood. Dalton discovered that the posterior cricoarytenoid muscles adducted the vocal cords during inspiration. He confirmed Flourens' observations that acute ablation of the cerebellum of pigeons caused loss of coordination. Dalton observed that properly cared for pigeons gradually recovered "coordinating power." Dalton observed that prolonged raised intracranial pressure caused tachycardia and then fatal bradycardia in dogs. Before Dalton published his photographic atlas of the human brain, neuroanatomy atlases were sketched by Europeans and imported into the United States. Dalton's atlas of the human brain contained precise photographs of vertical and horizontal sections that equal modern works. Before Dalton introduced live demonstrations of animals, physiology was taught by recitation of texts only. Dalton was the first American-born professor to teach physiology employing demonstrations of live animals operated on under ether anesthesia. He wrote an essay advocating experimentation on animals as the proper method of acquiring knowledge of function and that humane animal experimentation would ultimately improve the health of man and animals. His eloquent advocacy for humane experimental physiology quelled attacks by contemporaneous antivivisectionists. Dalton was America's first experimental neurophysiologist.

Parenchymal mean transit time analysis of 99mTc-DTPA captopril renography.

UNLABELLED: Proposed renal hemodynamic mechanisms of captopril suggest that quantitation of renographic retention parameters should help identify patients suspected of having renovascular disease. The parenchymal mean transit time (MTT) is theoretically superior to other measures of retention, but data supporting its superiority are few. METHODS: Two groups of subjects were studied with diethylenetriamine pentaacetic acid (DTPA) baseline and captopril renography, one (n = 43) with demographically defined essential hypertension (group I) and the other (n = 60) with a high prevalence of renovascular disease (group II). Abnormal parenchymal MTT values were derived from the statistical confidence limits of group I data and then applied to group II subjects for comparison with angiographic results. RESULTS: Depending on the sensitivity of the threshold chosen, specificity varied, but the overall accuracy of baseline parenchymal MTT for renovascular hypertension detection ranged from 54% to 58%. Change in parenchymal MTT (post-captopril - pre-captopril) accuracy was 55%-61% and was not significantly different. Neither method improved on previously reported quantitative or qualitative criteria. Group II subjects had significantly worse renal function than did group I subjects, and 23% had nondiagnostic renograms. CONCLUSION: Parenchymal MTT analysis of DTPA captopril renography is not more accurate and offers no advantages compared with qualitative renography or with more commonly used renographic measures in our subjects. This may relate to the high prevalence of renal dysfunction in our population. In subjects with renal dysfunction, the low sensitivity and the trend toward low specificity of parenchymal MTT do not support its routine use for the evaluation of renovascular disease among patients suspected of having renovascular hypertension.

Measurement of effective renal plasma flow: a comparison of methods.

We have compared two in vitro methods and three variations of kidney background (BG) subtraction within a gamma camera method (41 examinations, 31 patients) for determination of effective renal plasma flow (ERPF) using 131I orthoiodohippurate (OIH). Method I: plasma samples at 20 and 45 min after OIH injection, ERPF = dose X slope/intercept; Method II: 45-min plasma sample, ERPF = -51.1 + 8.21x + 0.019x2, x = dose/45-min plasma activity/I. Individual kidney and total ERPF were determined from gamma camera (GC) methods using renal uptake 1-2 min after injection. All methods were compared against Method I (previously validated against paraaminohippurate (PAH) clearances). Method II, which requires one blood sample is more accurate than GC methods. GC methods are insensitive to operator variability in placement of renal and BG regions of interest. They may be useful to follow changes in relative or total ERPF, but accurate depth correction of renal data is suggested. In vitro, blood sample-based methods are more accurate.

Exercise renography in untreated subjects with essential hypertension.

UNLABELLED: Exercise induced renal dysfunction is reported to occur in treated hypertensive patients but not seen normotensive subjects. It is unclear if this phenomenon is related to the disease or to treatment. METHODS: Four normal volunteers and 15 hypertensive subjects (antihypertensive medications were discontinued for more than 4 wk) were studied with upright radionuclide renography at rest and during bicycle exercise. The amount of exercise was sufficient to increase the heart rate at least 20 bpm above the resting value. All subjects were healthy, without evidence of left ventricular hypertrophy renal disease or hypertensive retinal disease. BUN, serum creatinine concentration and urinalysis were normal in all subjects. Renograms were performed for 12-15 min after injection of either 1 mCi[123]orthoidohippurate (OIH) or 2-7 mCi 99mTc-mercaptoacetyltriglycine (MAG3). Visual analysis and mean transit time calculation were performed on the rest and exercise studies. RESULTS: Seven of 14 hypertensive subjects and none of the normal volunteers demonstrated abnormal prolongation in renal transit during exercise which was not seen on the resting renogram. Four of these seven subjects had a history of hypertension for 2 yr or less. CONCLUSION: About 50% of individuals with mild-to-moderate hypertension and normal renal function may have abnormal renal transit of renal excretion agents during exercise, although their baseline studies are normal. This finding is unassociated with therapy and appears to be related directly to the pathophysiology of essential hypertension.

Prospective study of simultaneous orthoiodohippurate and diethylenetriaminepentaacetic acid captopril renography. The Einstein/Cornell Collaborative Hypertension Group.

UNLABELLED: Captopril renography (CR) has been established in the past 10 yr as a useful diagnostic test for renovascular hypertension. However, direct comparison of tubular and glomerular tracers, quantitative criteria, comparison of quantitative and qualitative results and the reliability of the results in renal failure have not been described in a systematic, prospective fashion. METHODS: Same-day baseline and CR using 99mTc-labeled diethylenetriaminepentaacetic acid (DTPA) and [131I]orthoiodohippurate (OIH) were simultaneously performed in two groups of hypertensive subjects, one with demographically defined essential hypertension (n = 43) and the other (n = 60) with a high prevalence of renovascular disease, defined with angiograms. Quantitative criteria for abnormal CR were derived from results among the subjects with essential hypertension. Qualitative analysis was performed using widely established criteria. RESULTS: There were no statistically significant differences between quantitative and qualitative accuracy, between OIH and DTPA or among quantitative parameters. The best accuracies for quantitative CR were 56% with DTPA (n = 57) and 60% with OIH (n = 60), in both cases using the relative renal uptake parameter. Qualitative CR (n = 60) had accuracies of 43% (DTPA) and 50% (OIH), both hindered by 29 (DTPA) and 25 (OIH) abnormal but nondiagnostic studies. Two false-positive studies were detected. Twenty-seven of 29 nondiagnostic studies were associated with a glomerular filtration rate of <50 ml/min (n = 17), one small kidney (n = 17) and/or bilateral renal artery stenosis (n = 16). Supplemental measurement of in vitro stimulated plasma renin activity insignificantly (p > 0.10) and improved accuracies to 63% (DTPA) and 70% (OIH), without introducing additional false-positive tests. CONCLUSION: Orthoiodohippurate and DTPA have comparable accuracy in prospective simultaneous evaluation of CR. False-positive studies are fewer than 5%. The accuracies of quantitative and qualitative criteria do not differ significantly but may be improved by supplemental use of the in vitro stimulated plasma renin activity. In individuals with renal insufficiency, small kidneys and/or bilateral renal artery disease, up to 48% of CR studies are abnormal but nondiagnostic.

Interventions in renal scintigraphy.

Physiological and pharmacological intervention for the purpose of determining organ functional reserve is a familiar concept in medical testing and in nuclear medicine. Nephrourologic applications include established procedures such as diuretic scintigraphy for determination of urinary outflow obstruction and captopril scintigraphy for determination of renovascular hypertension. Subtle renal dysfunction may exist among some individuals with essential hypertension, induced by provocative exercise renography, and not observed at rest. The strength of nuclear medicine resides in its ability to assess disorders of organ function for the diagnostic, prognostic, or pathophysiological information provided. Nephrourologic interventions are reviewed with an emphasis on the functional changes caused by the intervention.

Parathyroid imaging: its current status and future role.

The management of autonomous (primary or tertiary) hyperparathyroidism is controversial for two important reasons: (1) Diagnosis of primary or tertiary hyperparathyroidism (as distinct from reactive or secondary hyperparathyroidism) has been revolutionized in the past 20 years as a result of routine inclusion of serum calcium concentration assays in serum multiautomated analysis, now obtained routinely for both hospitalized as well as ambulatory patients. The prevalence of primary hyperparathyroidism in the general population has appeared to rise as a consequence of this assay and the enhanced detection of this disease. This situation has confused the management of hyperparathyroidism since most patients now present with asymptomatic disease, and the need for surgical treatment is controversial in asymptomatic individuals. (2) Primary hyperparathyroidism usually is caused by hypersecretion of parathyroid hormone by an autonomously functioning parathyroid adenoma. In a small percentage of cases, multigland hyperplasia is present. In experienced hands, surgical removal of an adenoma within the thyroid bed cures the hyperparathyroidism 90% to 95% of the time, without performance of a preoperative procedure to localize the adenoma. Approximately 10% of parathyroid tissue is ectopic in location, however. Furthermore, approximately two thirds of "missed" adenomas are within the thyroid bed. Reexploration in the event of a failed operation therefore is not an uncommon occurrence. Parathyroid localization procedures clearly are indicated in patients with primary hyperparathyroidism who have evidence of persistent disease after a failed attempt at surgical cure. In patients first presenting with primary hyperparathyroidism, the need for a localization procedure is less clear, since surgery appears to be successful much of the time without it. Regardless of the nature of the above controversies, surgery for autonomous hyperparathyroidism continues, and localization procedures become more popular. Preoperative localization procedures such as angiography and venography with venous sampling for parathormone are cumbersome and invasive. Noninvasive tests to localize the parathyroid glands have emerged in the past 10 years, including dual tracer radionuclide scintigraphy with 201-thallous chloride and 99m-technetium pertechnetate, high-resolution computer tomography, and fine parts ultrasonography. Dual tracer scintigraphy with thallium and technetium is reported to have a localization sensitivity of 70%-90%. False-negative studies occur primarily in patients with small adenomatous or hyperplastic glands.(ABSTRACT TRUNCATED AT 400 WORDS)

Interventions in renal scintirenography.

Nuclear nephrourology continues to develop and expand on traditional provocative physiological maneuvers, such as diuretic and captopril renography. In addition, newer interventions are conceived, such as aspirin renography, which test new and fascinating aspects of renal functional reserve. Since the last review of this topic in 1991, nephrourologic nuclear medicine has made considerable progress in diverse ways. Captopril and diuresis renography have made strides in establishing greater consensus of interpretation and procedure. Commonplace aspirin, the ubiquitous wonder drug, has revealed an unexpected role in renography by way of its inhibition of prostaglandin E2. Finally, further investigations of exercise renography in essential hypertension have deepened the plausibility of a renal role in the etiology of perhaps 50% of affected individuals.

Differential diagnosis and management of renovascular hypertension through nuclear medicine techniques.

Identification of patients with renovascular hypertension (RVH) among the larger group of patients with essential hypertension has been aided by a wide variety of in vitro and in vivo nuclear medicine procedures. The most valuable in vitro procedure remains the radioimmunoassay (RIA) for renin activity obtained from individual renal vein catheterization studies. Lateralizing renin activity provides valuable prognostic information about the likelihood for surgical cure of RVH. Older in vivo procedures for the diagnosis of RVH included rectilinear scanning and probe renography, which suffered from poor resolution and specificity, respectively. These tests have been replaced by computer-interfaced gamma camera scintirenography using 131I- or 123I-labeled orthoiodohippurate (OIH), or scintiangiography using 99mTc-DTPA. False-positive (FP) results for RVH persist due to a wide variety of relatively common conditions that can cause asymmetric renal size and function, including outflow obstruction and parenchymal renal disease. Newer approaches promise to improve the specificity of nuclear medicine procedures for identification of RVH. In particular, the number of FP exams appears to improve when scintirenography is performed before and after the administration of oral angiotensin converting enzyme (ACE) inhibitors, using either 99mTc-DTPA or OIH. The incentive for improved diagnostic testing has increased with the availability of percutaneous transluminal angioplasty (PCTA) for treatment of renal artery stenosis (RAS). Follow up of PCTA with scintirenography is of great value in assessing its effect on renal function and in evaluating the subsequent clinical course of the patient.

Consensus report on quality control of quantitative measurements of renal function obtained from the renogram: International Consensus Committee from the Scientific Committee of Radionuclides in Nephrourology.

Among all the physiological indices that can be quantified using renography, measurement of renal function is the most basic. These measurements are used to make critical clinical management decisions and, as such, their reliability needs to be quality assured. This article seeks to address each aspect of the renography procedure, with particular emphasis on the effect on measurement of relative renal function. Estimation of individual kidney function is mentioned, but only briefly. A consensus approach was adopted, overseen, and directed by a chairman appointed by the Scientific Committee of the International Radionuclides in Nephro-Urology Group. The chairman selected the panel of experts from eight different countries based on their practical experience in the field. Where evidence exists to support the various recommendations it is given. Otherwise, the stated guidance represents the considered opinion of a body of experts, based on long experience and unpublished data. Some necessary compromises were made to account for the fact that renography is seldom performed solely with the purpose of measuring relative renal function. The technicalities of renography have always been a source of debate in nuclear medicine, which is reflected by the fact that a consensus could simply not be reached on a small number of issues. The structure of the report ensures that these are clearly indicated. This should serve to highlight gaps in our current knowledge, thus helping to direct future research. It is envisaged that the recommendations will be revised on a 2-year cycle to ensure that they remain up to date. An "open" process will be used to encourage participation and ownership. It is hoped that promotion of these guidelines, suitably complemented by audit processes, will raise standards in the practice of gamma camera renography.

The Einstein/Cornell collaborative protocol to assess efficacy and methodology in captopril scintirenography. Early results in patients with essential hypertension. Report of the Einstein/Cornell Collaborative Hypertension Group.

We have established an ongoing prospective investigation of hypertensive patients to examine the rates of false results in captopril scintirenography. This study is being conducted at the Albert Einstein College of Medicine and the Cornell University Medical Center. Two large populations will allow an accurate assessment of both false positive and false negative results. We report here the results from the first 30 patients, results which will be useful in defining the bounds for future studies.

Neurophysiological study of subacute combined degeneration.

Three patients with subacute combined degeneration of the spinal cord due to vitamin B12 deficiency showed a characteristic pattern of abnormalities on neurophysiological tests which corresponded to the clinical signs and symptoms. Peripheral nerve conduction studies showed an axonal degeneration peripheral neuropathy. Brain stem auditory evoked responses were normal; visual evoked responses were mildly abnormal and somatosensory evoked responses were moderately abnormal. These studies shed light on the pathology of this disorder and can aid in its diagnosis.

Diuretic renography and angiotensin converting enzyme inhibitor renography.

Renovascular hypertension and renal outlet obstruction are two clinical conditions well evaluated by nuclear medicine techniques. They both require a specific intervention to challenge a specific aspect of renal functional reserve. Diuretic renography is the oldest common example in nuclear medicine where functional change in the kidney is provoked for diagnostic purposes. The kidney's tubular functional reserve, in this instance, is challenged to induce diuresis and increase urine flow. This intervention permits diuretic renography to retain an essential role in the evaluation of hydroureteronephrosis. Captopril renography is a more recent example of a similar principle and depends on a reactive renin-angiotensin system to identify a kidney responsible for RVH. In both renal outlet obstruction and RVH, an anatomic abnormality is also identified (hydronephrosis and RAS, respectively) at some point in the diagnostic workup. The final diagnosis in each instance, however, depends on evidence for a functional disorder, provoked and measured during the radionuclide interventional examination. These serve as excellent examples of the power of functional imaging to identify specific medical disorders.

Spatial disorientation and the Dyke-Davidoff-Masson syndrome.

A patient with Dyke-Davidoff-Masson Syndrome had a lifelong history of spatial disorientation and visual-spatial cognitive defects demonstrated by psychological tests. We suggest that the abnormalities of behavior and test performance may be related atrophic lesions demonstrated by pneumoencephalography and computerized axial tomography. We consider several explanations to account for the lack of compensation for these cognitive defects.

The contributions of Dr. Roswell Park to epilepsy and spinal surgery.

ROSWELL PARK, M.D., (1852-1914) is remembered for founding the world's first cancer institute that now bears his name a century ago, The Roswell Park Cancer Institute, and for an unfortunate association with the mortal wounding of President William McKinley in Buffalo, NY, in 1901. Park's accomplishments as a pioneer American neurosurgeon have been overlooked. After Park was appointed as Chair of Surgery at the University of Buffalo in 1884, he became the first American surgeon to precisely localize and remove a posttraumatic epileptic focus in the absence of external scars in 1886. Park introduced American physicians and surgeons to David Ferrier's research on localization of cerebral cortical function and Victor Horsley's techniques for extirpating epileptic foci. In 1895, Park became the first American surgeon to successfully treat spina bifida. In the same year, he wrote the first American monograph on surgery of the head. Park's case reports of successful operations on patients deemed almost incurable reveal boldness and ingenuity. Park's untimely death truncated a promising career.

Orbital involvement as the initial manifestation of sarcoidosis: magnetic resonance imaging findings.

A 74-year-old man had diplopia, painful right ophthalmoplegia, proptosis, conjunctival injection, and facial skin lesions. Magnetic resonance imaging (MRI) revealed infiltration of the right intraorbital adipose tissue. Lesions were mixed low- and high-signal on T2-weighted images and enhanced on fat-suppressed T1-weighted postcontrast images. A skin biopsy revealed numerous noncaseating granulomas consistent with sarcoidosis. Treatment with corticosteroids and chlorambucil led to a full clinical recovery. Sarcoidosis should be considered in the evaluation of orbital pseudotumor in elderly patients, even if no systemic manifestations of sarcoidosis are present.