Showing papers in "Annals of Neurology in 1984"

Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes: a distinctive clinical syndrome.

Abstract: We report on two patients who have a mitochondrial myopathy, encephalopathy, lactic acidosis, and recurrent cerebral insults that resemble strokes (MELAS). These two and nine other reported patients share the following features: ragged red fibers evident on muscle biopsy, normal early development, short stature, seizures, and hemiparesis, hemianopia, or cortical blindness. Lactic acidemia is a common finding. We believe that MELAS represents a distinctive syndrome and that it can be differentiated from two other clinical disorders that also are associated with mitochondrial myopathy and cerebral disease: Kearns-Sayre syndrome and the myoclonus epilepsy ragged red fiber syndrome. Existing information suggests that MELAS is transmitted by maternal inheritance. The ragged red fibers suggest an abnormality of the electron transport system, but the precise biochemical disorders in these three clinical syndromes remain to be elucidated.

A quantitative model for the in vivo assessment of drug binding sites with positron emission tomography.

Abstract: We propose an in vivo method for use with positron emission tomography (PET) that results in a quantitative characterization of neuroleptic binding sites using radiolabeled spiperone. The data are analyzed using a mathematical model that describes transport, nonspecific binding, and specific binding in the brain. The model demonstrates that the receptor quantities Bmax (i.e., the number of binding sites) and KD-1 (i.e., the binding affinity) are not separably ascertainable with tracer methodology in human subjects. We have, therefore, introduced a new term, the binding potential, equivalent to the product BmaxKD-1, which reflects the capacity of a given tissue, or region of a tissue, for ligand-binding site interaction. The procedure for obtaining these measurements is illustrated with data from sequential PET scans of baboons after intravenous injection of carrier-added (18F)spiperone. From these data we estimate the brain tissue nonspecific binding of spiperone to be in the range of 94.2 to 95.3%, and the regional brain spiperone permeability (measured as the permeability-surface area product) to be in the range of 0.025 to 0.036 cm3/(s X ml). The binding potential of the striatum ranged from 17.4 to 21.6; these in vivo estimates compare favorably to in vitro values in the literature. To ourmore » knowledge this represents the first direct evidence that PET can be used to characterize quantitatively, locally and in vivo, drug binding sites in brain. The ability to make such measurements with PET should permit the detailed investigation of diseases thought to result from disorders of receptor function.« less

The neurobiology of vascular head pain.

Abstract: Nervous connections between the trigeminal ganglia and cerebral blood vessels have recently been identified in experimental animals and have been termed the trigeminovascular system. Existence of this system in humans is inferential. Trigeminovascular neurons and their peripheral unmyelinated nerve fibers contain the neurotransmitter peptide substance P. Most newly synthesized substance P is transported from ganglion cell bodies to afferent nerve fibers, where depolarization-induced release of neurotransmitter into the wall of the cerebral blood vessel occurs. Substance P dilates pial arteries, increases vascular permeability, and activates cells that participate in the inflammatory response. The relationship of trigeminovascular fibers to the pathogenesis of vascular head pain sheds light on possible mechanisms of migraine and other central nervous system conditions associated with headache and inflammation.

Monoclonal antibody analysis of mononuclear cells in myopathies. I : Quantitation of subsets according to diagnosis and sites of accumulation and demonstration and counts of muscle fibers invaded by T cells

Abstract: In 76 muscle specimens (normal controls, 9; Duchenne dystrophy, 11; scleroderma, 11; dermatomyositis, 13; polymyositis, 15; inclusion body myositis, 17), mononuclear cells were analyzed at perivascular, perimysial, and endomysial sites of accumulation. Monoclonal antibodies reactive for B cells, T cells, T cell subsets, killer (K) or natural killer (NK) cells, and the Ia antigen were used for cell typing. Macrophages were identified by the acid phosphatase reaction. Few extravascular mononuclear cells occurred in normal muscle. In all inflammatory myopathies, a mixed exudate of T cells, B cells, and macrophages was present. Mature K/NK cells were rare in all diseases. In dermatomyositis, polymyositis, and inclusion body myositis, there was a positive gradient for T cells, T8+ cells, and activated T cells and a negative gradient for B cells and T4+ cells between perivascular and endomysial sites. In scleroderma the predominant perimysial exudate consisted mostly of T cells and macrophages. The percentage of B cells at all sites, and the T4+/T cell ratio in the endomysium, were significantly higher in dermatomyositis than in the other diseases. In polymyositis and inclusion body myositis, the endomysial exudate contained a large number of T cells, T8+ cells, and activated T cells but only sparse B cells. T cells accompanied by macrophages focally surrounded and invaded nonnecrotic fibers in polymyositis and inclusion body myositis. Rare fibers in Duchenne dystrophy and a very few fibers in dermatomyositis and scleroderma were similarly affected. We infer that (1) T-B, T-T, and T-macrophage cooperativities are likely to exist in muscle in different myopathies; (2) T cell-mediated fiber injury plays a role in polymyositis and inclusion body myositis; (3) T cell-mediated fiber injury can also occur in inherited diseases, such as Duchenne dystrophy; and (4) a local humoral response may occur in muscle in dermatomyositis and possibly in polymyositis and inclusion body myositis.

Alzheimer's disease: A study of epidemiological aspects

Abstract: A case-control study was performed to determine the possible roles of various environmental factors, prior illnesses, drug use, and personal habits in the development of Alzheimer's disease. Such information was collected from 40 patients with onset of dementia prior to age 70 and from 80 community control subjects matched for age, sex, and race. No significant differences were found between patients and control subjects in toxic environmental exposures, animal contacts, smoking, drinking, or unusual dietary habits. A significantly higher frequency of prior thyroid disease was found in women patients than in women control subjects (25.0% and 7.1%, respectively). A history of severe head injury was also obtained significantly more often among the patients than among the controls (15.0% and 3.8%, respectively). Aside from these differences, which may prove to be important associative factors in this illness, there appeared to be no major premorbid demographic or clinical factors associated with this form of dementia. There was evidence, however, of a genetic factor that was manifested in an excess of dementia and mental retardation (including Down's syndrome) in families of patients with Alzheimer's disease.

A progressive familial encephalopathy in infancy with calcifications of the basal ganglia and chronic cerebrospinal fluid lymphocytosis

Abstract: Eight infants developed a progressive disorder of the central nervous system with bilateral spasticity and dystonia, acquired microcephaly, and a rapid course toward profound deterioration and death. All the patients had abnormal cerebrospinal fluid with mild but persistent lymphocytosis. Computed tomography showed various combinations of bilateral symmetrical calcifications in the basal ganglia, progressive brain atrophy, and deep white matter hypodensities, the first two being present in all families but not in every individual patient. The disorder is familial and probably genetic in origin, although some features, especially the pleocytosis, may erroneously suggest an inflammatory condition.

Cortical abnormalities in Alzheimer's disease

Abstract: Regional cerebral glucose metabolism, an index of neuronal activity, was compared in 20 patients with Alzheimer's disease and 8 age-matched normal volunteers by positron emission tomography following [18F]2-fluoro-2-deoxy-D-glucose administration. Overall cortical glucose utilization in the Alzheimer's group was 10 to 49% below that of control individuals. The posterior parietal cortex and contiguous portions of posterior temporal and anterior occipital lobes were most severely affected; frontal cortex was relatively spared. This pattern of cortical involvement is consistent with the major clinical features of Alzheimer's disease. Comparison of patients with early and more advanced dementia suggested that a substantial decline in glucose metabolism occurs before cognitive impairment becomes evident; once the patient is symptomatic, however, small additional metabolic decrements are associated with a marked deterioration in intellectual function.

Epidemiology of parkinsonism: Incidence, classification, and mortality

Abstract: An epidemiological study of parkinsonism over a 13-year period (1967 through 1979) is presented, updating previous reports on incidence and trend in the population of Rochester, Minnesota. The overall average annual incidence of parkinsonism per 100,000 population was 20.5, adjusted to the 1970 total United States population, which is virtually unchanged from previous observations. Incidences calculated for each calendar year (1967 through 1979) revealed no remarkable change following the 1976 swine flu vaccination program. There was no sex difference and the peak incidence occurred between ages 75 and 84 years. Idiopathic Parkinson's disease was the most common variant (86%), followed by drug-induced parkinsonism (7%). There were no new cases of postencephalitic parkinsonism diagnosed during the study period. Relative frequency of other types of Parkinson's disease as identified by practicing neurologists is presented. For each case two age- and sex-matched controls were selected from the Rochester population. The survival rates in the controls were comparable to the general population of the west north central region of the United States. The mortalities in the patients were significantly higher (p = 0.001) than the controls and were unchanged from previous rates reported from the same community. In the 69 (50%) patients treated with levodopa, the mortality was comparable to that in controls. The favorable outcome in these cases is attributed to bias resulting from selection of healthier patients for treatment.

Baclofen in the treatment of trigeminal neuralgia: Double-blind study and long-term follow-up

Abstract: A double-blind crossover study of the effects of baclofen was conducted on 10 patients with typical trigeminal neuralgia. Baclofen significantly decreased the number of painful paroxysms in 7 of the 10 patients. An open trial in another 50 patients with trigeminal neuralgia refractory to or unable to tolerate carbamazepine showed that 37 (74%) were relieved of their attacks by baclofen, either alone (12 patients) or in combination with previously ineffective doses of carbamazepine or phenytoin (25). On long-term follow-up of one to five years (mean, 3.0 years), 18 of the 60 patients (30%) continued pain free while receiving baclofen; 10 (17%) went into remission after 3 to 6 months; 13 (22%) became refractory to baclofen after 1 to 18 months; and 2 (3%) elected operation despite a good response to baclofen. The results indicate that baclofen is a useful drug in the treatment of trigeminal neuralgia.

Monoclonal antibody analysis of mononuclear cells in myopathies. II: Phenotypes of autoinvasive cells in polymyositis and inclusion body myositis.

Abstract: In 6 cases of polymyositis and 6 of inclusion body myositis, phenotypes of mononuclear cells focally surrounding and invading muscle fibers were analyzed. By localizing the T8, T4, and Ia markers with direct immunofluorescence and acid phosphatase enzyme cytochemically in the same sections, five different phenotypes were simultaneously identified in a given section: T8+ and T4+ cells that were either activated (Ia+) or not activated (Ia-), and acid phosphatase--reactive and Ia+ macrophages. This approach permitted the separate and quantitative assessment of the distributions of the different phenotypes among the invading versus the surrounding cells. In both polymyositis and inclusion body myositis, the invading cells were selectively enriched in the T8+ phenotype. One-third of all invading cells and one-half of the invading T8+ cells were activated. T4+ cells were more abundant among the surrounding than the invading cells, and only a small proportion of the T4+ cells were activated. These findings are especially significant in view of the cytotoxic capability of the T8+ cells and because histocompatibility factors permit T8+ but not T4+ cells to recognize an antigen on muscle fibers. Macrophages accounted for 21 to 31% of the cells invading or surrounding nonnecrotic fibers. For purposes of comparison, we also analyzed mononuclear cells in necrotic fibers: 80% of these cells were macrophages, and only 20% were T cells. The findings indicate that in polymyositis and inclusion body myositis, nonnecrotic muscle fibers are injured by autoinvasive T8+ cells that act in concert with macrophages. Further, the findings strongly imply previous sensitization of clones of T cells to muscle fiber-associated surface antigen(s).

Long-term corticosteroid treatment of myasthenia gravis: Report of 116 patients

Abstract: One hundred sixteen patients, aged 8 to 82 years, with myasthenia gravis were treated with prednisone, 60 to 80 mg daily, until the onset of improvement, followed by lower-dose alternate-day therapy of several years' duration. Of all patients, 80.2% achieved either remission (27.6%) or marked improvement (52.6%). Moderate improvement occurred in 14.7%, and 5.2% showed no improvement. Increasing age correlated with a favorable outcome, but sex, duration of illness prior to treatment, severity and distribution of weakness at the time of onset of treatment, and presence of thymoma were not factors in the response to therapy.

Human brain glucose utilization and cognitive function in relation to age

Abstract: Brain oxidative metabolism was examined with positron emission tomography and [18F]2-deoxy-D-glucose in 40 healthy men aged 21 to 83 years, under conditions of reduced visual and auditory stimulation. The mean cerebral metabolic rate for glucose (CMRglc) equaled 4.6 to 4.7 mg X 100 gm-1 X min-1 and did not correlate significantly with age (p greater than 0.05). Regional cerebral metabolic rates for glucose (rCMRglc) and Q ratios (rCMRglc/CMRglc), which had lower coefficients of variation than did rCMRglc, also did not correlate with age. Hyperfrontality of cerebral metabolism was absent at all ages. Age decrements were demonstrated in the error score on the Benton Revised Visual Retention Test and in the Performance Subtest scaled score of the Wechsler Adult Intelligence Scale (WAIS) but not in the Verbal Subtest scaled score of the WAIS. The cognitive test scores did not correlate with brain metabolic rates. The results indicate that brain oxidative metabolism, when measured under resting conditions with reduced sensory input, is not reduced in relation to age in healthy men. Furthermore, no significant relations between intelligence and resting cerebral metabolism are evident.

Myasthenia gravis and myasthenic syndromes

Abstract: More than a decade ago myasthenic symptoms were observed in rabbits immunized with acetylcholine receptor (AChR) [119] and AChR deficiency was found at the neuromuscular junction in human myasthenia gravis (MG) [36]. By 1977 the autoimmune character of MG and the pathogenic role of AChR antibodies had been established by several measures. These included the demonstration of circulating AChR antibodies in nearly 90% of patients with MG [87], passive transfer with IgG of several features of the disease from human to mouse [149], localization of immune complexes (IgG and complement) on the postsynaptic membrane [30], and the beneficial effects of plasmapheresis [20, 123]. Substantial subsequent progress has occurred in understanding the structure and function of AChR and its interaction with AChR antibodies. The relationships of the concentration, specificities, and functional properties of the antibodies to the clinical state in MG have been carefully analyzed, and the mechanisms by which AChR antibodies impair neuromuscular transmission have been further investigated. The clinical classification of MG has been refined, the role of the thymus gland in the disease has been further clarified, and new information has become available on transient neonatal MG. The prognosis for generalized MG is improving, but there is still no consensus on its optimal management. Novel therapeutic approaches to MG are now being explored in animal models. Recognition of the autoimmune origin of acquired MG also implied that myasthenic disorders occurring in a genetic or congenital setting had a different cause. As a result, a number of congenital myasthenic syndromes have come to be recognized and investigated. Finally, an acquired disorder of neuromuscular transmission different from MG, the Lambert-Eaton myasthenic syndrome, has also been shown to have an autoimmune basis. In this syndrome, active zone particles of the presynaptic membrane are direct or indirect targets of the pathogenic autoantibodies.

Selective memory improvement and impairment in temporal lobectomy for epilepsy

Abstract: Reexamination of 23 patients 1 year after elective anterior temporal lobectomy for intractable complex partial (psychomotor) seizures showed a reduction in certain memory functions combined with an improvement in others. Both improvement and impairment in selective memory functions were related to the degree of postoperative seizure reduction as well as to the side of the remaining temporal lobe. The results imply that uncontrolled seizures interfered with the memory functions of the temporal lobe contralateral to the epileptogenic focus.

High blood glucose level on hospital admission and poor neurological recovery after cardiac arrest.

Abstract: To evaluate the relationship between blood glucose and neurological recovery after cardiac arrest, we retrospectively reviewed our experience with 430 consecutive patients resuscitated after out-of-hospital cardiac arrest. All these patients had received variable amounts of intravenous 5% glucose solutions before admission. Awakening patients, those following commands or having comprehensible speech, were classified as to whether they suffered persistent neurological deficits. The mean blood glucose level on hospital admission was higher in 154 patients who never awakened than in 276 who did awaken (mean, 341 versus 262 mg per 100 milliliters; p less than 0.0005). Among the 276 who awakened, 90 patients with persistent neurological deficits had higher mean glucose levels on admission than did 186 without deficits (286 versus 251 mg per 100 milliliters; p less than 0.02). These significant differences persisted after excluding all patients whose glucose levels were higher than 500 mg per 100 milliliters and after controlling for potentially confounding variables using multiple regression analysis.

Age‐related differences in brain electrical activity of healthy subjects

Abstract: A combined neurophysiological (electroencephalographic [EEG] and sensory evoked potential) and neuropsychological investigation was performed on 63 healthy men ranging in age from 30 to 80 years. Although alpha frequency diminished slightly with age, neither amplitude nor frequency demonstrated a high age correlation. Alpha blocking, in contrast, did correlate with age, in the direction of reduced alpha reactivity. EEG background activity underwent significant age-correlated change, consisting of reductions in slow activity and augmentation of fast activity i.e., EEG desynchronization. Previously reported age-related EEG slowing may be related to the presence of disease in the populations studied. Topographic analysis revealed that the greatest change occurred in the temporal lobes. More change was noted either early or late in the age span, suggesting that aging is a nonlinear process. More features were derived from the right hemisphere than from the left, suggesting that the aging process is not completely symmetrical.

Parkinson's disease: Neuron loss in the nucleus basalis without concomitant Alzheimer's disease

Abstract: A representative region of the nucleus basalis of Meynert was investigated in 11 patients with idiopathic Parkinson's disease and compared with the identical region in 13 age-matched control subjects. Simultaneously, the cerebral cortex and the nucleus basalis in the patients with Parkinson's disease were examined for senile plaques and Alzheimer's neurofibrillary tangles. The nucleus basalis was significantly depleted of its large neurons in Parkinson's disease (p less than 0.001 versus controls; Student t tests), but in the majority of cases the neuron loss was not associated with Alzheimer's disease.

Brain electrical activity in patients with presenile and senile dementia of the Alzheimer type.

Abstract: Neurophysiological and behavioral data obtained from 9 patients with presenile dementia and 10 with senile dementia of the Alzheimer type were compared with similar data from 25 age- and sex-equivalent controls. Compared with the healthy controls, both patients groups demonstrated increased background electroencephalographic slowing with a reduction in fast activity (synchronization). Topographic analyses of data from electroencephalographic and evoked potential studies indicate that areas of maximal group differences between the presenile patients and their controls include the right posterior temporal and, to a lesser extent, left midtemporal to anterior temporal areas, whereas the maximal differences between the senile patient group and their controls involve the midfrontal and anterior frontal lobes, bilaterally. Moreover, right-sided numerical features derived from topographic maps proved most useful in differentiating the presenile patients and their age-matched controls, whereas bilateral features were more useful in separating senile patients from their controls. These topographic dissimilarities between patient groups suggest that an age-disease interaction exists between patients with presenile and senile dementia of the Alzheimer type. Correlational analyses between neuropsychological test scores and neurophysiological features indicate that increased slowing and decreased fast activity were associated with poorer test performance.

Physiological responses to focal cerebral ischemia in humans.

Abstract: Positron emission tomography (PET) was used to investigate the regional hemodynamic and metabolic changes that accompany focal reductions in cerebral blood flow to ischemic but uninfarcted regions of the brain. Studies were performed on 7 patients chosen from a larger group of subjects with transient ischemic attacks and normal computed tomographic findings, specifically because their PET studies showed decreased blood flow to the symptomatic hemisphere rather than symmetrical flow to the two hemispheres. In regions with decreased blood flow, the cerebral metabolic rate for oxygen was also decreased, but to a lesser degree. Cerebral blood volume, vascular mean transit time, and fractional extraction of oxygen from blood were all increased. These findings indicate that cerebral oxygen metabolism was maintained in the face of decreased blood flow by local compensatory mechanisms that included dilation of intraparenchymal blood vessels and increased transfer of oxygen from blood to tissue. Such knowledge of the physiological characteristics of ischemic, uninfarcted brain is important if PET is to be used clinically to differentiate reversible cerebral ischemia from irreversible infarction.

Adrenoleukodystrophy: survey of 303 cases: biochemistry, diagnosis, and therapy

Abstract: Adrenoleukodystrophy (ALD) is a genetically determined disorder associated with progressive central demyelination and adrenal cortical insufficiency. All affected persons show increased levels of saturated unbranched very-long-chain fatty acids, particularly hexacosanoate (C26:0), because of impaired capacity to degrade these acids. This degradation normally takes place in a subcellular organelle called the peroxisome, and ALD, together with Zellweger's cerebrohepatorenal syndrome, is now considered to belong to the newly formed category of peroxisomal disorders. Biochemical assays permit prenatal diagnosis, as well as identification of most heterozygotes. We have identified 303 patients with ALD in 217 kindreds. These patients show a wide phenotypic variation. Sixty percent of patients had childhood ALD and 17% adrenomyeloneuropathy, both of which are X-linked, with the gene mapped to Xq28. Neonatal ALD, a distinct entity with autosomal recessive inheritance and points of resemblance to Zellweger's syndrome, accounted for 7% of the cases. Although excess C26:0 in the brain of patients with ALD is partially of dietary origin, dietary C26:0 restriction did not produce clear benefit. Bone marrow transplant lowered the plasma C26:0 level but failed to arrest neurological progression.

The risk of intracerebral hemorrhage during oral anticoagulant treatment: a population study.

Abstract: In a retrospective study of 166 patients, all admitted to the University Hospital, Leiden, The Netherlands, between January 1, 1970 and December 31, 1979, we estimated the relative risk of intracerebral hemorrhage from oral anticoagulant therapy. The risk was more than ten times higher for patients over 50 years of age than for similarly aged untreated individuals in the general population. Within this age group the risk was influenced by neither age nor sex. Hypertension, present in 80% of the patients, was the most important predisposing condition; the risk of bleeding rose with increasing intensity of anticoagulation. There was no substantial difference in clinical condition at onset, rate of progression, mortality, or degree of recovery between patients with anticoagulant-associated hemorrhage and those with spontaneous intracranial hemorrhage.

Principles and pitfalls of nerve conduction studies.

Abstract: This report reviews the fundamental principles and the changing concepts of nerve stimulation techniques, and discusses the proper application of these techniques in the differential diagnosis of peripheral nerve disorders. Nerve conduction studies help delineate the extent and distribution of the neural lesion and distinguish two major categories of peripheral nerve disease: demyelination and axonal degeneration. Although the method is based on simple principles, pitfalls abound in practice. Variability in nerve conduction measurement may result from temperature change, variations among nerve segments, and the effects of age. Other sources of error include excessive spread of stimulation current, anomalous innervation, temporal dispersion, and inaccuracy of surface measurement. Unlike a bipolar derivation, which selectively records near-field potentials, a referential recording may give rise to stationary far-field peaks from a moving source. Overlooking this possibility can lead to an incorrect interpretation of findings. Conventional nerve conduction studies deal primarily with measurements of the distal nerve segments in an extremity. More recent techniques are applicable to less accessible anatomical regions, as illustrated by elicitation of the blink reflex, F wave, and H reflex, and the use of the inching technique. Other methods used to assess special aspects of nerve conduction include the ischemic test and studies of slow-conducting fibers.

Regional cortical dysfunction in Alzheimer's disease as determined by positron emission tomography.

Abstract: Local cerebral glucose metabolism and psychometric function were compared in 17 patients with Alzheimer's disease and 5 healthy age-matched controls. Performance on tests of global intellectual function averaged 30 to 45% lower in the Alzheimer's group. Mean cortical glucose metabolism, as determined by positron emission tomography following fluorine-18-labeled fluorodeoxyglucose administration, was reduced by 30% in the Alzheimer's group. There was a significant positive correlation between the degree of overall dementia and the amount of metabolic reduction. The distribution of cortical hypometabolism was not uniform: the posterior parietal lobes and contiguous portions of the posterior temporal and anterior occipital lobes were most severely involved. The frontal cortex was relatively spared. These findings are compatible with the major clinical deficits found in patients with Alzheimer's disease and may help focus future biochemical probes into the pathophysiology of this disease.

Classic and generalized variants of Pick's disease: A clinicopathological, ultrastructural, and immunocytochemical comparative study

Abstract: Six sporadic cases of dementia with lobar atrophy and neuronal cytoplasmic inclusions (Pick's disease) could be separated into two groups on the basis of the involvement of subcortical structures, the distribution and the histochemical, immunochemical, and ultrastructural characteristics of the inclusions, and possibly the age at onset. The first group (classic) was characterized by predominantly cortical atrophy and the presence in the hippocampus and neocortex of argyrophilic cytoplasmic inclusion bodies that reacted with a monoclonal antibody against neurofilament proteins and antitubulin antisera. Ultrastructurally the bodies were composed of straight fibrils of variable diameter, averaging 15 nm, and long-period constricted fibrils. The second group (generalized) showed subcortical as well as cortical atrophy. Cortical and subcortical cytoplasmic inclusions contained RNA and stained poorly with silver and antibodies against neurofilaments and microtubules. Ultrastructurally the straight fibrils composing the bodies were coated with granular material, presumed to be derived from ribosomes. The generalized cases occurred in younger patients than did the classic cases in this series.

Patterns of local cerebral glucose utilization determined in Parkinson's disease by the [18F]fluorodeoxyglucose method.

Abstract: [18F]Fluorodeoxyglucose scans were performed on 9 patients with Parkinson's disease and 14 normal subjects. Five patients were restudied after an interval of 3 to 4 years. We found no selective metabolic change in striatum, where dopamine deficit is known to be greatest, in affected patients; cerebral glucose metabolism was reduced uniformly throughout the parkinsonian brain (average 18% decrease). With increased severity of bradykinesia and the development of mild to moderate dementia, global brain metabolism in Parkinson's disease decreased further. In one moderately demented patient with Parkinson's disease, severe parietal cortex hypometabolism was found, similar to that seen in Alzheimer's disease. In contrast, mildly to moderately demented patients with Huntington's disease have marked caudate hypometabolism, but cerebral glucose metabolism is normal elsewhere. It appears that in addition to the well-known neurotransmitter loss in the nigrostriatal system, there is an abnormal metabolic process involving neurons throughout the parkinsonian brain.

Neurological disorders associated with deficiency of glutamate dehydrogenase.

Abstract: Glutamate dehydrogenase (GDH) activity was measured in leukocytes from 88 patients with various types of degenerative neurological disorders affecting primarily the cerebellum and/or the basal ganglia, and 26 healthy control subjects. Twelve patients with slowly progressive multiple-system atrophic disorders were found to have a partial deficiency of this enzyme (52% of control level). The majority of these patients evidenced a constellation of neurological findings consistent with the diagnosis of olivopontocerebellar atrophy, although others were atypical in their neurological manifestations. Thus, GDH-deficient patients were encountered with predominantly extrapyramidal manifestations (atypical Parkinson's disease), cerebellar dysfunction with peripheral neuropathy, or anterior horn cell signs, suggesting that a pleomorphic phenotypic expression of the enzymatic deficiency may occur. Seven cases of GDH deficiency were familial and 5 were sporadic. The former patient group consisted of siblings of either sex, but no parents or offspring were affected. The genetic pattern of the disorder is compatible with autosomal recessive inheritance. Patients with dominantly inherited olivopontocerebellar atrophy or other types of cerebellar or basal ganglia degenerative neurological disorders showed normal GDH activity. Leukocyte GDH was fractionated into "particulate-heat labile" and "soluble-heat stable" components. In the patients the decrease in activity was limited to the "particulate-heat labile" component. A genetic mutation of a GDH "isoenzyme" may occur in some patients with multiple-system degeneration.

Kindling: an animal model of complex partial epilepsy.

Abstract: Kindling is an animal model of complex partial epilepsy induced by focal electrical stimulation of the brain. This paper describes the phenomenon and underscores the limited nature of current insights into its basic mechanisms. Anatomical delineation of the underlying neural network is a necessary first step for elucidating the basic cellular and molecular mechanisms. Recent evidence suggests that the substantia nigra may be a crucial component of the network underlying limbic kindled seizures and possibly kindling itself.

Focal cerebral ischemia in the rat: topography of hemodynamic and histopathological changes.

Abstract: We studied local cerebral blood flow, as measured by autoradiography with digital image processing and by tissue morphology, in six rats 4 hours after occlusion of the proximal middle cerebral artery. A consistent, three-dimensional pattern of graded reductions in local cerebral blood flow involved the affected hemisphere, with a densely ischemic zone (local cerebral blood flow less than 3 ml/100 gm/min) in the dorsolateral caudate putamen and the adjacent frontoparietal cortex. In the frontoparietal cortex, the normal laminar pattern of local cerebral blood flow was disrupted, and there was a transcortical gradient in flow, with pronounced ischemia in deeper layers and relatively preserved superficial flow. Comparisons of autoradiographic findings with histopathological abnormalities in adjacent frozen sections showed that the region of ischemic damage corresponded closely with the area of greatest reduction in blood flow. Although around this region local cerebral blood flow increased centrifugally, a striking finding was that flow density changed abruptly (a tenfold variation in flow within a 1 to 2 mm interval) at the edge of the pathological lesion. Penumbral conditions may therefore exist in only a very narrow zone 4 hours after onset of focal ischemia. After occlusion of a major cerebral artery, the pattern of local cerebral blood flow changes appears to depend on interactions among vascular architecture, reductions in perfusion pressure, alterations in metabolic demands, and variations in local vascular resistance.

Contralateral cerebellar hypometabolism following cerebral insult: A positron emission tomographic study

Abstract: Positron emission tomographic studies of 16 patients with cerebral ischemia and brain tumor showed asymmetries in cerebellar metabolism not encountered in 14 normal control subjects. An asymmetry was present in 62.5% of cases. The lower metabolic rate occurred in the cerebellar hemisphere contralateral to the cerebral lesion (p less than 0.001; sign test). In all cases computed tomography showed the supratentorial lesion to be unilateral and the posterior fossa contents to be unaffected. The presence of depressed cerebellar metabolism was highly associated with involvement of the contralateral parietal lobe (p less than 0.02; phi coefficient). The presence of a cerebellar abnormality was not related to the presence of any particular sign. Serial studies showed normalization of cerebellar metabolism over time. It is likely that this effect is a result of interruption of the functional interconnections between the cerebrum and the cerebellum.