Showing papers in "JAMA Neurology in 1991"
TL;DR: A critical review of both earlier and more current clinical observations that raise the possibility that the cerebellum may contribute to the modulation of higher order behavior is presented, as well as a review of the salient laboratory data that appear to support this contention.
Abstract: • Recent clinical and research reports suggest that the cerebellum may contribute to the modulation of higher order behavior. This article presents a critical review of both earlier and more current clinical observations that raise this possibility, as well as a review of the salient laboratory data that appear to support this contention. It also summarizes the relevant anatomic work concerning the contributions to the cortico-pontocerebellar pathways from the higher order cerebral association areas, which have been implicated as partial anatomic substrates for this putative cerebellar role in higher function. Finally, it provides a framework for the understanding of this correlation, concludes with suggestions for future areas of investigation, and recommends that patients with cerebellar lesions be studied from a neurobehavioral point of view.
927 citations
TL;DR: It is suggested that tests for delayed recall may be particularly useful in the early detection of Alzheimer's disease and should be considered in screening batteries for dementia in community surveys.
Abstract: • The present study was designed to determine which of the memory tasks included in the CERAD ( C onsortium to E stablish a R egistry for A lzheimer's D isease) neuropsychological battery best differentiate patients with early Alzheimer's disease from cognitively normal elderly control subjects and also best distinguish between the various levels of severity of the dementia process. A sample of CERAD patients with Alzheimer's disease was stratified by disease severity into those with mild, moderate, or severe dementia and matched with control subjects for sex, age, and education. Using multivariate procedures and cutting scores, the efficacy of each memory measure in distinguishing between these groups and control subjects was determined. The test for delayed recall was found to be the best overall discriminatory measure. The other tests of memory, ie, immediate recall, intrusion errors, and recognition memory, had poor overall discriminability. None of the CERAD memory measures were found to be particularly powerful in staging the severity of dementia. These findings suggest that tests for delayed recall may be particularly useful in the early detection of Alzheimer's disease and should be considered in screening batteries for dementia in community surveys.
740 citations
TL;DR: The Short Test of Mental Status was compared with standardized tests of cognitive function such as the Wechsler Adult Intelligence Scale, Mattis Dementia Scale, and the Auditory Verbal Learning Test, and showed a high degree of correlation.
Abstract: • The Short Test of Mental Status can be administered to patients in inpatient and outpatient settings in approximately 5 minutes, and it contains items that test orientation, attention, immediate recall, arithmetic, abstraction, construction, information, and delayed (approximately 3 minutes) recall. The test was administered to a group of demented community patients and their age- and sex-matched control subjects. Using an age-adjusted approach, sensitivity of the test to identifying dementia is 86.4, with a specificity of 93.5. The test was compared with standardized tests of cognitive function such as the Wechsler Adult Intelligence Scale, Mattis Dementia Scale, and the Auditory Verbal Learning Test, and showed a high degree of correlation. Group means and standard deviations for subtest items and total score are presented for control subjects (n=138), demented patients (n 130), and patients with memory impairment only (n = 20). Percentile scores for subtest items in control subjects are also provided.
326 citations
TL;DR: It was showed that self-rating of memory disturbance by older adults may be related more to depressed mood than to poor performance on memory tests.
Abstract: Complaints of poor memory by patients may be an early symptom of a pathologic process like Alzheimer's disease. It is therefore important to determine if patients' complaints of memory impairments are an accurate reflection of real memory disturbance. The relationship between memory complaints (metamemory) and objective memory performance, mood, age, verbal intelligence, and sex was examined in a group of 199 healthy, community dwelling adults (39 to 89 years old). Memory complaints demonstrated a stronger association with depressed mood than with performance on memory tests. Increasing reports of depressive symptoms were associated with more overall memory complaints. Verbal intelligence, age, and sex also contributed to memory complaints. Patients with higher verbal intelligence reported fewer complaints and placed less emphasis on forgetting. Older individuals reported greater frequency of forgetting and greater frequency of using memory techniques. Specific types of memory complaints, seriousness of forgetting, and types of memory aids employed are also described. These results showed that self-rating of memory disturbance by older adults may be related more to depressed mood than to poor performance on memory tests.
306 citations
TL;DR: The results suggest that hemispheric specialization of function may be anomalous in this population and raise the possibility that some language- and learning-impaired children may have additional volume reductions in cortical and subcortical structures.
Abstract: Using magnetic resonance imaging 20 language- and learning-impaired children were compared with 12 normal control subjects. Gross brain structure was remarkably normal in the language- and learning-impaired group. Semiautomated morphometry was used to measure hemispheric volumes and cerebral asymmetries in six cerebral regions. The volume of the left posterior perisylvian region was significantly reduced in language- and learning-impaired children. Asymmetries in inferoanterior and superoposterior cerebral regions were also significantly different in this group. Results of descriptive group comparisons of estimated volumes of other cerebral gray-matter structures raise the possibility that some language- and learning-impaired children may have additional volume reductions in cortical and subcortical structures. The results suggest that hemispheric specialization of function may be anomalous in this population.
269 citations
TL;DR: It is concluded thatprednisone produces a rapid increase in muscle strength in patients with Duchenne dystrophy and that this improvement is maximal at a prednisone dosage of 0.75 mg/kg or less.
Abstract: • A randomized, controlled trial of daily prednisone was conducted in 99 boys (aged 5 to 15 years) with Duchenne dystrophy to define the time course of improvement and the dose response to treatment. Prednisone at 0.3 mg/kg (n=33), prednisone at 0.75 mg/kg (n = 34), and placebo (n = 32) were administered for 6 months. Patients were examined using manual muscle and myometry testing, timed functional testing, pulmonary function testing, and laboratory measurements at 10 days, 1 month, 2 months, 3 months, and 6 months of treatment. Boys treated with prednisone had stronger average muscle strength scores, than did boys treated with placebo as early as 10 days after starting therapy. At the 3-month visit, the boys in the group given 0.75 mg/kg of prednisone were significantly stronger than those in the group given 0.3 mg/kg of prednisone, indicating a dose response. At 6 months, significant side effects occurred in the group treated with 0.75 mg/kg of prednisone, including weight gain, cushingoid appearance, and excessive hair growth. Only weight gain was observed in the group taking prednisone at a dose of 0.3 mg/kg. Importantly, no side effects were evident at 10 days or 1 month of treatment, despite improvement in muscle strength and function. We conclude that prednisone produces a rapid increase in muscle strength in patients with Duchenne dystrophy and that this improvement is maximal at a prednisone dosage of 0.75 mg/kg or less.
267 citations
TL;DR: The profile of neuropathologic and neurochemical changes associated with psychosis is distinct from that previously reported for major depression in the context of primary dementia.
Abstract: • Neuropathologic and neurochemical correlates of psychosis were determined using brain tissue from 27 autopsy-confirmed cases of Alzheimer's disease. The densities of senile plaques and neurofibrillary tangles were determined in the middle frontal and superior temporal cortex, the prosubiculum, and the entorhinal cortex of the hippocampus. The concentrations of norepinephrine, dopamine, and serotonin, the metabolites of these biogenic amines, and the specific activity of choline acetyltransferase were also determined in these four cortical regions as well as in the substantia nigra, thalamus, amygdala, and caudate nucleus. Psychosis was associated with significantly increased densities of senile plaques and neurofibrillary tangles in the prosubiculum and middle frontal cortex, respectively, with trends toward increased densities of these lesions in the other areas examined. This finding is consistent with the increased rate of cognitive decline that accompanies this behavioral disorder. Psychosis was also associated with the relative preservation of norepinephrine in the substantia nigra, with trends in this direction for five of the remaining seven brain regions examined, and a significant reduction of serotonin in the prosubiculum that was accompanied by trends toward reduced levels of serotonin and 5 hydroxyindoleacetic acid in the remaining regions. The profile of neuropathologic and neurochemical changes associated with psychosis is distinct from that previously reported for major depression in the context of primary dementia.
261 citations
TL;DR: The areas of six bilateral brain segments in the right and left hemispheres and the area of subdivisions of the corpus callosum were measured to suggest an anatomic abnormality in the angular gyrus region.
Abstract: • The areas of six bilateral brain segments in the right and left hemispheres, on a horizontal brain section, and the area of subdivisions of the corpus callosum, on a midsagittal brain section, were measured on magnetic resonance images obtained from 21 dyslexic and 29 control subjects. In the entire group, the frontal half of the horizontal brain section showed asymmetry, with the right side being larger, whereas posteriorly only the occipital polar segment was asymmetrical, with the left side being larger. Dyslexic subjects exhibited asymmetry, with the right side greater than the left side, in contrast to the relatively symmetrical pattern that is normally observed in the midposterior segment that corresponds to the angular gyrus. In the corpus callosum, dyslexic subjects were found to have a larger splenium than nondyslexic subjects, and dyslexic female subjects were found to have a larger splenium than dyslexic male subjects. Because transcallosal pathways connecting the left and right angular gyrus regions traverse through the splenium of the corpus callosum, the above findings in dyslexic subjects suggest an anatomic abnormality in the anaular gyrus region.
260 citations
TL;DR: A trial of grafting of adrenal chromaffin tissue into the putamen, supported by infusion of nerve growth factor in a 63-year-old woman with a 19-year history of Parkinson's disease, now complicated by on-off phenomena and drug-induced hyperkinesia.
Abstract: Experimental studies in rodents show that beta-nerve growth factor can increase the survival, neurite outgrowth, and functional effect of grafts of adrenal chromaffin cells to the basal ganglia. We, therefore, have begun to investigate whether treatment with nerve growth factor might also increase the functional effect of autografts of adrenal medullary tissue in patients with Parkinson's disease. Previous studies have shown that stereotactic implantation of adrenal tissue pieces produces a transient functional improvement that lasts for a few months. This report describes a trial of grafting of adrenal chromaffin tissue into the putamen, supported by infusion of nerve growth factor. The patient is a 63-year-old woman with a 19-year history of Parkinson's disease, now complicated by on-off phenomena and drug-induced hyperkinesia, despite optimized medical management. The left adrenal gland was removed, and the medulla was dissected into 1- to 2-mm3 pieces in a solution containing nerve growth factor purified from mouse submandibular gland. Pieces were implanted in six tracts 3 to 4 mm from a previously placed cannula in the left putamen. Through the cannula, nerve growth factor was infused for 23 days for a total dose of 3.3 mg. Clinical assessment consisted of global ratings for rigidity and/or hypokinesia and for drug-induced hyperkinesia. Measures of gait and fine-motor control were also made. The motor readiness potential and auditory evoked potentials were recorded.(ABSTRACT TRUNCATED AT 250 WORDS)
223 citations
TL;DR: Men tended to have a slower disease progression than did women, and this was particularly evident among men inheriting Huntington's disease from affected mothers, and neither the butyrophenone haloperidol nor the tricyclic antidepressant imipramine were related to rate of progression.
Abstract: • The rate of disease progression was assessed for 42 persons affected by Huntington's disease who had been neurologically examined at least six times and followed up for at least 3 years. Disease progression was assessed by a disability rating scale administered at each examination. Slow progression was associated with older age at onset of disease and with heavier weight (body mass index) at the first examination. Men tended to have a slower disease progression than did women, and this was particularly evident among men inheriting Huntington's disease from affected mothers. Neither the butyrophenone haloperidol nor the tricyclic antidepressant imipramine were related to rate of progression. Assessments of depression, hostility, and tobacco use were also unrelated to rate of progression. Clinical trials in Huntington's disease should consider these factors when designing therapeutic studies.
213 citations
TL;DR: The clinical use of NMDA antagonists may prove useful in Parkinson's disease to treat symptoms and retard disease progression and there is evidence that the beneficial effects of anticholinergic drugs and amantadine may be mediated by NMDA receptor blockade.
Abstract: Current long-term treatment of Parkinson's disease is inadequate, and improved symptomatic and neuroprotective therapies are needed. Recent interest has focused on the use of antagonists of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor in Parkinson's disease. Abnormally increased activity of the subthalamic nucleus is postulated to play a central pathophysiological role in the signs of Parkinson's disease, and NMDA antagonists may provide a means of decreasing this activity selectively. Like dopaminergic agonists, NMDA antagonists can reverse the akinesia and rigidity associated with monoamine depletion or neuroleptic-induced catalepsy. Very low doses of NMDA antagonists markedly potentiate the therapeutic effects of dopaminergic agonists. There is evidence that the beneficial effects of anticholinergic drugs and amantadine may be mediated, in part, by NMDA receptor blockade. Moreover, NMDA antagonists provide profound protection of dopaminergic neurons of the substantia nigra in the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and methamphetamine models of Parkinson's disease. The clinical use of NMDA antagonists may prove useful in Parkinson's disease to treat symptoms and retard disease progression.
TL;DR: Data support the likelihood that iron plays a role in the modulation of dopamine binding to postsynaptic receptors and iron are also concentrated in oligodendrocytes in normal brain and, thus, may have a function in myelination.
Abstract: • Aberrant iron metabolism in the brain is typified by Hallervorden-Spatz syndrome. In this disorder, large amounts of iron are deposited in the globus pallidus and the pars reticulata of the substantia nigra. It is characterized by extrapyramidal dysfunction, as demonstrated by dystonia, rigidity, and choreoathetosis; onset during the first two decades of life; and progression of signs and symptoms. Corroborative findings include corticospinal tract involvement, ie, spasticity and extensor toe signs, progressive intellectual impairment, retinitis pigmentosa and optic atrophy (usually associated visual evoked response and electroretinogram abnormalities), seizures, familial occurrence, hypointense areas in the basal ganglia on magnetic resonance imaging scans (particularly in the substantia nigra), abnormal cytosomes in circulating lymphocytes, and sea-blue histiocytes in bone marrow. Iron function in normal brain metabolism is manifold, but high concentrations of iron in the basal ganglia area may signal a unique relationship. Data support the likelihood that iron plays a role in the modulation of dopamine binding to postsynaptic receptors. In addition, transferrin receptors and iron are also concentrated in oligodendrocytes in normal brain and, thus, may have a function in myelination. A role of iron also seems likely in oxidation and peroxidation reactions involving membranes and DNA, a capability that becomes uncontrolled when protective biologic mechanisms become inadequate.
TL;DR: Leuko-araiosis on the magnetic resonance imaging scan, unlike its correlate on the computed tomographic scan, was not shown to relate to cognitive decline or to the presence of focal abnormalities on neurologic examination, likely to reflect the heterogeneity of the changes detected with magnetic resonance Imaging and their limited extent in subjects.
Abstract: • We report our observations on the clinical and radiologic correlates of changes in cerebral white matter based on 94 subjects undergoing magnetic resonance imaging in a prospective study of dementia. Periventricular hyperintensity occurred twice as often in patients with Alzheimer's disease as in healthy control subjects. Within the control group, the presence of periventricular hyperintensity correlated significantly with one measure of cerebral atrophy and with the presence of changes in the adjoining deep white matter. The significance of white-matter changes distinct from the ventricles (leuko-araiosis) remains unsettled. Leuko-araiosis on the magnetic resonance imaging scan, unlike its correlate on the computed tomographic scan, was not shown to relate to cognitive decline or to the presence of focal abnormalities on neurologic examination. This is likely to reflect the heterogeneity of the changes detected with magnetic resonance imaging and their limited extent in our subjects.
TL;DR: It is demonstrated that the filaments in IBM share properties with amyloid proteins, which raises the likely possibility that the Filaments represent a modification of a normal protein within an acidic degradative vacuolar compartment.
Abstract: • Inclusion body myositis (IBM) represents a serious debilitating disease of muscle without identifiable cause or treatment. Muscle biopsy specimens have characteristic rimmed vacuoles, varying degrees of inflammation, and, most importantly, cytoplasmic and intranuclear filamentous inclusions of unknown composition. Fresh-frozen sections of muscle biopsy specimens from 24 IBM cases were stained with Congo red dye (pH, 10.5 to 11.0). Control biopsy specimens included polymyositis, dermatomyositis, hereditary vacuolar myopathies of unknown cause, acid maltase deficiency, distal myopathy, oculopharyngeal dystrophy, and chloroquine myopathy. Sections were also immunostained with antibody to transthyretin, human P component, and immunoglobulin light chains. In the vacuolated fibers in IBM, amyloidogenic green-birefringent deposits were seen. Some deposits were delicate and wispy appearing, and others were plaque-like. The size of deposits varied, measuring 1 × 2 to 8 μm, and rarely up to 20 μm in length. The number of amyloid-positive fibers correlated with the number of vacuolated fibers. Similar deposits were seen in one case of distal myopathy and one hereditary vacuolar myopathy. Other control cases were negative for amyloid deposits. Antibody staining for known amyloidogenic proteins was negative. This study demonstrates that the filaments in IBM share properties with amyloid proteins. The location implies that this amyloid material is formed intracellularly, rather than having a systemic derivation. The association of amyloid deposits with autophagic vacuoles in IBM raises the likely possibility that the filaments represent a modification of a normal protein within an acidic degradative vacuolar compartment. An alternative possibility, considering the shared properties of IBM filaments and prions (which include size and amyloidogenic properties), is that IBM represents a human prion disease. Further studies will be required to resolve the nature of the amyloidogenic filaments in IBM, but these findings may provide clues to the pathogenesis of this poorly understood disorder. In addition, the findings should facilitate the clinical diagnosis of IBM.
TL;DR: Patients with idiopathic intracranial hypertension who did not have papilledema are described and initial management should include removal of possible inciting agents, weight loss if applicable, and standard headache therapy.
Abstract: • We describe 10 patients with idiopathic intracranial hypertension who did not have papilledema. Idiopathic intracranial hypertension without papilledema, although rarely reported, may well be a clinically important headache syndrome. Historical and demographic features of patients with idiopathic intracranial hypertension without papilledema are similar to those of patients with papilledema. Obese women with chronic daily headache and symptoms of increased intracranial pressure, pulsatile tinnitus, history of head trauma or meningitis, an empty sella on imaging studies, or a headache that is unrelieved by standard therapy should have a diagnostic lumbar puncture. Findings from laboratory and neurologic investigations are normal in most patients with idiopathic intracranial hypertension without papilledema. Initial management should include removal of possible inciting agents, weight loss if applicable, and standard headache therapy. Lumbar puncture and diuretic therapy should precede a trial of corticosteroids. Surgery (lumboperitoneal or ventriculoperitoneal shunt or perhaps optic nerve sheath fenestration) may be indicated for prolonged incapacitating headache that is not responsive to medical management or lumbar puncture.
TL;DR: A significant association between aspiration and pharyngeal residue observed under videofluoroscopy and cranial nerve IX abnormality, vocal fold weakness, and severe dysarthria is revealed.
Abstract: We studied 23 individuals (16 men, seven women; mean age 57 years) who had brainstem strokes confirmed by computed tomography of the head or magnetic resonance imaging. Videofluoroscopic modified barium-swallowing examination showed aspiration in 15 of 23 patients. Of the 15 aspirating patients, the majority had bilateral strokes with multiple lesion loci, most often in association with large-vessel disease. All 15 patients had involvement of the pons or medulla. Statistical analyses revealed a significant association between aspiration and pharyngeal residue observed under videofluoroscopy, cranial nerve IX abnormality, vocal fold weakness, and severe dysarthria. Despite initial severity, recovery was good. Following an aggressive program of aspiration prevention, over 80% of patients resumed full oral nutrition at the last follow-up.
TL;DR: The role of heart rate power spectral analysis as a clinical test of autonomic function in patients with known or suspected autonomic failure is supported.
Abstract: Power spectral analysis of the heart rate was compared with standard tests of autonomic function performed on 15 insulin-dependent diabetic patients with symptoms of autonomic dysfunction. The high-frequency power, low-frequency power, and total power of the heart rate power spectrum measured in the supine position--possible measures of parasympathetic nervous system function--were significant predictors of the expiratory-inspiratory ratio, the beat-to-beat heart rate difference on deep respiration, the standard deviation of the resting heart rate, the 30:15 ratio, and the Valsalva ratio. The change in low-frequency power on moving from the supine to upright position, a possible measure of sympathetic nervous system function, was a modest predictor of the systolic and diastolic blood pressure fall in response to postural change, but a poor predictor of the blood pressure response to isometric exercise and a cold stimulus. This study supports the role of heart rate power spectral analysis as a clinical test of autonomic function in patients with known or suspected autonomic failure.
TL;DR: Results are presented from six patients treated with tetrathiomolybdate for up to 8 weeks as initial therapy with Wilson's disease, and none of the five patients who had presented with acute neurological symptoms worsened.
Abstract: Patients with Wilson's disease who present with acute neurological symptoms often become clinically worse when initially treated with penicillamine. Other available anticopper drug therapies do not appear to offer a solution to this treatment problem. We are developing and evaluating a new drug, ammonium tetrathiomolybdate for this purpose. Theoretically, tetrathiomolybdate has optimal properties, including an immediate blockade of copper absorption and the property of forming complexes with copper in the blood, rendering the copper nontoxic. In this article, we present results from six patients treated with tetrathiomolybdate for up to 8 weeks as initial therapy. None of the five patients who had presented with acute neurological symptoms worsened. Also presented are methods of assay, preliminary stability studies, and methods of evaluating therapeutic end points with respect to copper metabolism.
TL;DR: The results confirm the presence of subtle neuropsychologic deficits and indicate a higher frequency of white matter signal abnormalities in essential hypertension, as shown on magnetic resonance imaging, but do not indicate a correlation of these findings with each other.
Abstract: To search for a morphologic basis of cognitive impairment possibly associated with essential hypertension, we studied 35 otherwise asymptomatic hypertensive individuals (mean age, 38.7 years; range, 22 to 49 years) and 20 normotensive control subjects (mean age, 37.9 years; range, 26 to 49 years) using neuropsychologic tests and magnetic resonance imaging. Irrespective of drug treatment, hypertensive individuals performed significantly worse than did control subjects when assessed for verbal memory and total learning and memory capacity, while there were no differences in test results of visual memory, attention, vigilance, and reaction time. The hypertensive individuals also described themselves as less active but ranked similar on five other mood subscales. Punctate high-signal intensities of the white matter were found almost twice as often in the hypertensive group (38%) as in the control group (20%). There was no difference in test performance between hypertensive individuals with and those without white matter lesions, however. Our results confirm the presence of subtle neuropsychologic deficits and indicate a higher frequency of white matter signal abnormalities in essential hypertension, as shown on magnetic resonance imaging, but do not indicate a correlation of these findings with each other.
TL;DR: It is believed that these changes, so commonly found on MRI scans in the elderly, reflect actual changes in the white matter but that their nature and clinical significance need to be elucidated.
Abstract: • Two types of high-signal intensity abnormalities are frequently found bilaterally in the cerebral white matter of brains of elderly patients on T 2 -weighted magnetic resonance imaging (MRI) scans. One is located in the immediate periventricular region; the other, in the deep subcortical white matter (centrum semiovale). The diagnostic implications of this second type continue to be uncertain. To determine the neuropathologic correlates of these lesions, the brains from seven elderly patients were fixed in buffered formaldehyde solution, subjected to MRI scanning, and examined neuropathologically. Variable degrees of bilateral periventricular (subependymal) sharply defined areas of high-signal intensity were found in all the brains, and the larger of these showed corresponding areas of myelin pallor with gliosis and dilated perivascular spaces. Discrete bilateral patches of high-signal intensity were found in the centrum semiovale in five patients. Myelin and axon stains showed varying degrees of diffuse white matter pallor in many areas examined, both with and without these areas of high-signal intensity on MRI scans. Neither the myelin nor the axon stains showed discrete white matter abnormalities that corresponded to the MRI findings. We believe that these changes, so commonly found on MRI scans in the elderly, reflect actual changes in the white matter but that their nature and clinical significance need to be elucidated.
TL;DR: In the younger age group, primarily infantile spasms and tonic-clonic seizures with myoclonus were observed, and the older patients often had partial simplex or partial complex seizures as well as Tonic-Clonic seizures.
Abstract: • The prevalence, onset, and type of seizure disorders, as well as seizure control, were studied in a large cohort of 405 individuals with Down syndrome (age range, 6 months to 45 years). The evaluation of a questionnaire completed by the subjects' parents and of the patients' medical records indicated that 33 (8.1%) of 405 persons with Down syndrome had seizure disorder. With regard to the onset of seizures, a bimodal distribution was noted: 40% of patients began having seizures before the age of 1 year, and another 40% started with seizure activity in the third decade of life. In the younger age group, primarily infantile spasms and tonic-clonic seizures with myoclonus were observed, and the older patients often had partial simplex or partial complex seizures as well as tonic-clonic seizures.
TL;DR: Although the relations of cognitive deterioration to disability in daily life and of burden experienced by the caregiver to patient's condition were stronger than often reported, it was impossible to deduce the overall severity of dementia from one single aspect.
Abstract: • In dementia there is cognitive impairment, disability in daily life, and sometimes behavioral disturbance. These changes are a burden for the caregivers of patients with dementia. Few studies are available that examine all these aspects and their interrelationships in a single patient group. In our study we selected detailed methods for assessment of all these aspects. Interrelationships were studied in 30 mild to moderately impaired patients with dementia and their caregivers. Although the relations of cognitive deterioration to disability in daily life and of burden experienced by the caregiver to patient's condition were stronger than often reported, it was impossible to deduce the overall severity of dementia from one single aspect. Thus, for effective management of patients and caregivers, for evaluation of individual treatment or of clinical trials, attention should be paid to all the different aspects of patients' condition and caregivers' burden. Outcome measurements will then be more valid.
TL;DR: Significantly associated with improvement were disease duration of less than 1 year, progression of weakness until treatment, absence of discrepancy in weakness between arms and legs, areflexia of the arms, and slowed nerve conduction velocity of the motor median nerve.
Abstract: • Of 52 patients fulfilling the criteria of chronic inflammatory demyelinating polyneuropathy, 20 (38%) did not improve after intravenous immunoglobulin treatment, two (4%) had a short-lasting improvement and subsequent infusions had no effect, nine (17%) reached a spontaneously or therapeutically induced complete remission, and 21 patients (40%) needed intermittent infusions to maintain improvement. All patients who improved initially had symptoms that significantly interfered with life-style. After treatment, 90% of these patients were independent in their daily activities. Significantly associated with improvement were disease duration of less than 1 year, progression of weakness until treatment, absence of discrepancy in weakness between arms and legs, areflexia of the arms, and slowed nerve conduction velocity of the motor median nerve. The probability of improvement if all these features are present is 93%.
TL;DR: Patients in a vegetative state sustained more severe closed-head injury as reflected by the Glasgow Coma Scale scores and pupillary findings and more frequently had diffuse injury complicated by swelling or shift in midline structures.
Abstract: To elucidate the clinical course of the vegetative state after severe closed-head injury, the Traumatic Coma Data Bank was analyzed for outcome at the time of discharge from the hospital and after follow-up intervals ranging up to 3 years after injury. Of 650 patients with closed-head injury available for analysis, 93 (14%) were discharged in a vegetative state. In comparison with conscious survivors, patients in a vegetative state sustained more severe closed-head injury as reflected by the Glasgow Coma Scale scores and pupillary findings and more frequently had diffuse injury complicated by swelling or shift in midline structures. Of 84 patients in a vegetative state who provided follow-up data, 41% became conscious by 6 months, 52% regained consciousness by 1 year, and 58% recovered consciousness within the 3-year follow-up interval. A logistic regression failed to identify predictors of recovery from the vegetative state.
TL;DR: It is suggested that the pseudotumor syndrome has a single underlying mechanism (disturbed CSF circulation) and that recognition of this mechanism not only clarifies the pathophysiologic processes of PTC but also has important diagnostic and therapeutic implications.
Abstract: • We report a series of eight cases that show a close resemblance to, but are not identical with, pseudotumor cerebri (PTC) as normally defined. The majority of these cases are characterized by raised intracranial pressure without ventriculomegaly. They include two cases of cranial venous outflow obstruction in which clinical or radiologic abnormalities precluded the diagnosis of PTC proper (cases 1 and 2); one case of chronic meningitis in which an abnormal cerebrospinal fluid (CSF) composition precluded the diagnosis of PTC (case 3); two cases without either papilledema or a measured increase of CSF pressure, which in other respects, particularly in response to treatment, resembled PTC (cases 4 and 5); and three cases of what is thought to represent an infantile form of PTC (cases 6 through 8). The purpose of the analysis of these cases is twofold. First, it is argued that these cases throw light on the mechanism of PTC itself, supporting a concept of a disturbance of CSF circulation in this condition, and that they are themselves illuminated by considerations of typical PTC. Second, the cases are used to frame a proposed classification of the pseudotumor syndrome aimed at broadening the diagnostic criteria applied currently to PTC. It is suggested that the pseudotumor syndrome has a single underlying mechanism (disturbed CSF circulation) and that recognition of this mechanism not only clarifies the pathophysiologic processes of PTC but also has important diagnostic and therapeutic implications.
TL;DR: It is suggested that the risk of developing Parkinson's disease is influenced by a variety of factors, and smoking was inversely associated with PD, as has been previously reported.
Abstract: • While the cause of Parkinson's disease (PD) remains unknown, recent evidence suggests that certain external factors, ie, environmental agents, may act as neurotoxins, initiating the chain of oxidative reactions that ultimately destroy neurons in the substantia nigra. Young-onset PD might result from greater exposure to a putative neurotoxin. This hypothesis has rekindled interest in the epidemiology of PD. We therefore conducted a detailed analysis of various environmental exposures and early life experiences in 80 patients with old-onset PD (at an age older than 60 years), 69 young-onset patients (younger than 40 years), and 149 age- and sex-matched control subjects. Contrary to previous reports, we were unable to implicate well water or exposure to herbicides, pesticides, or industrial toxins as significant PD risk factors. A residential history of rural living was reported by more patient cases than control subjects and was marginally significant. On the other hand, at least one episode of head trauma "severe enough to cause vertigo, dizziness, blurred or double vision, seizures or convulsions, transient memory loss, personality changes, or paralysis" occurred significantly more often prior to disease onset in patients with both young-onset and old-onset PD than in control subjects (odds ratio=2.7). When adjusted for head trauma and rural living, smoking was inversely associated with PD, as has been previously reported (odds ratio=0.5). There were no significant differences in early life experiences or environmental exposures between young-onset and old-onset patients. We suggest that the risk of developing PD is influenced by a variety of factors. While we were unable to link specific environmental agents with PD, our study suggests that head trauma should be reassessed as a potential risk factor for PD.
TL;DR: Disaggregated ventral mesencephalic tissue from single aborted human fetuses was implanted stereotaxically into a consistent striatal site in 12 patients with advanced Parkinson's disease, and further trials are needed to identify host factors influencing outcome.
Abstract: • Disaggregated ventral mesencephalic tissue from single aborted human fetuses of 11 to 18 weeks' gestation was implanted stereotaxically into a consistent striatal site in 12 patients with advanced Parkinson's disease. All were receiving optimum levodopa therapy and were examined preoperatively and at 3,6,9, and 12 months postoperatively. Immunosuppression was not used. There were significant sustained improvements at 12 months in three patients; motor fluctuations were absent in two. There were modest group improvements up to 6 months, with increased quality of "on" and "off" phases, quantity of on times, and specific improvements in contralateral upper limb bradykinesia. Preoperative levodopa requirements were reduced to a mean of 64% at 6 months and 61% at 12 months. Deterioration below baseline ratings occurred in three of nine patients who had consistent follow-up to 12 months. Grafting of midgestational human fetal tissue can lead to improvement in Parkinson's disease. Individual disease severity may be critical, and further trials are needed to identify host factors influencing outcome.
TL;DR: The germinoma represents a less malignant form of germ cell tumor that appears in the pineal, suprasellar, and periventricular regions and may involve endocrine, hypothalamic, visual, and cognitive dysfunction.
Abstract: • The germinoma represents a less malignant form of germ cell tumor. Depending on the individual's age, this neoplasm constitutes approximately 0.1% to 3.4% of all intracranial tumors. The embryologic origin remains a mystery; however, current theories implicate an aberration in primordial germ cell migration. Clinical presentation depends on tumor location and may involve endocrine, hypothalamic, visual, and cognitive dysfunction. In evaluating midline intracerebral masses, it is imperative that one be aware of the various radiologic appearances, endocrinologic changes, and chemical markers that help to distinguish germinomas from other neoplasms that appear in the pineal, suprasellar, and periventricular regions. Only through the careful evaluation of all available studies can the physician institute appropriate therapies such as biopsy, radiation, and chemotherapy. This article focuses on the epidemiology, embryology, clinical presentation, means of diagnosis, treatment, and outcome of this rare neoplasm.
TL;DR: The rare appearance of the different dyskinesias and normal movements under similar circumstances during sleep could be a result of common effects on the generator systems or changes in the excitability of the final common motor pathway.
Abstract: • The effect of sleep on the involuntary movements or dyskinesias in Parkinson's disease, Huntington's disease, primary and secondary torsion dystonia, and Gilles de la Tourette syndrome was studied in a total of 52 patients and 10 normal subjects using video electroencephalographic telemetry. Movements typical of the wake pattern were seen occasionally during unequivocal sleep in all but two completed studies, and in each condition reappeared under similar circumstances. The movements were most likely to occur after awakenings or lightenings of sleep, or in stage one sleep. The movements were very rare during the deeper phases of sleep. Those movements that occurred during sleep without awakenings were usually preceded by arousal phenomena and, rarely, by sleep spindles or slow waves. The control group showed normal "semipurposeful" movements under the same conditions during sleep. The rare appearance of the different dyskinesias and normal movements under similar circumstances during sleep could be a result of common effects on the generator systems or changes in the excitability of the final common motor pathway.
TL;DR: The data suggest that focal abnormalities in muscarinic binding in vivo may characterize some patients with Alzheimer's disease and Pick's disease, but further studies are needed to address questions about partial volume artifacts and receptor quantification.
Abstract: • A high-affinity muscarinic receptor antagonist, 123 IQNB (3-quinuclidinyl-4-io-dobenzilate labeled with iodine 123), was used with single photon emission computed tomography to image muscarinic acetylcholine receptors in 14 patients with dementia and in 11 healthy controls. High-resolution single photon emission computed tomographic scanning was performed 21 hours after the intravenous administration of approximately 5 mCi of IONB. In normal subjects, the images of retained ligand showed a consistent regional pattern that correlated with postmortem studies of the relative distribution of muscarinic receptors in the normal human brain, having high radioactivity counts in the basal ganglia, occipital cortex, and insular cortex, low counts in the thalamus, and virtually no counts in the cerebellum. Eight of 12 patients with a clinical diagnosis of Alzheimer's disease had obvious focal cortical defects in either frontal or posterior temporal cortex. Both patients with a clinical diagnosis of Pick's disease had obvious frontal and anterior temporal defects. A region of interest statistical analysis of relative regional activity revealed a significant reduction bilaterally in the posterior temporal cortex of the patients with Alzheimer's disease compared with controls. This study demonstrates the practicability of acetylcholine receptor imaging with 123 IQNB and single photon emission computed tomography. The data suggest that focal abnormalities in muscarinic binding in vivo may characterize some patients with Alzheimer's disease and Pick's disease, but further studies are needed to address questions about partial volume artifacts and receptor quantification.