Autologous Unpurged Bone Marrow Transplantation for Acute Non Lymphoblastic Leukemia in First Remission

Forty consecutive adult patients under the age of 50 with acute non-lymphoblastic leukemia (ANLL) in first complete remission, underwent autologous bone marrow transplantation (ABMT) between March 1984 and April 1990. The conditioning regimen employed included cyclophosphamide and total body irradiation, followed by the administration of unpurged ABMT. The median time from diagnosis to transplant was 7 months (3-15 months), and the median time from complete remission to ABMT was 4 months (range 3-9 months). Twenty-two (51%) patients remain in complete remission 6-81 months (median 24 months) after ABMT.

The causes of death were, recurrent leukemia (11 patients), parenchymal toxicities such as acute respiratory distress syndrome and veno-occlusive disease (3 patients), hemorrhage (2 patients) and infection (2 patients). Eleven patients relapsed after 3-12 months (median 5 months). This study has produced survival data comparable to those of other institutions employing TBI for either allo or autotransplants.     

Autologous bone marrow transplantation as adjuvant treatment for high-risk Hodgkin's disease in first complete remission after MOPP/ABVD protocol.

Fifteen patients with very poor prognosis Hodgkin's disease in remission after MOPP/ABVD regimen, were treated with high-dose chemotherapy (HDC) and autologous marrow transplantation (ABMT) immediately after achieving complete remission (CR). Thirteen patients (86.6%) remain alive in unmaintained CR at a median time of 36 months (range 10-64 months) post-transplant. In the other two patients reasons for failure included relapse of Hodgkin's disease (one patient) and death due to interstitial pneumonitis secondary to carmustine therapy. These patients were compared with a historical control group consisting of 24 patients with the same poor prognostic factors, who achieved CR with MOPP/ABVD and did not receive other treatment. Eight out of 24 patients (33%) remain alive and well in unmaintained CR at a median time of 42 months (range 19-83 months). The administration of MOPP/ABVD combined with HDC and ABMT was not associated with an increased incidence of major toxicity. The results achieved support the early sequential treatment of a highly effective drug combination followed by HDC/ABMT that can substantially improve the likelihood of cure in these advanced stage very poor prognosis Hodgkin's disease patients.     

Long-term sequelae of prefrontal cortex damage acquired in early childhood

Frontal lobe dysfunction is often invoked as a contributing factor in developmental disorders characterized by chronic maladaptive behavior, but interpretation of relevant neuropsychological findings has been hampered by the limited information available regarding the consequences of focal prefrontal damage early in life. We describe here the long-term behavioral and cognitive sequelae of damage to prefrontal cortex in two young adult patients who had sustained their brain damage prior to 16 months of age. In the context of normal neurological examinations, both cases had remarkable histories of impaired decision making, behavioral dyscontrol, social defects, and abnormal emotion. Performances were primarily normal on a broad range of neuropsychological measures (intellect, memory, language, academic achievement, visual perception, and visuoconstruction), but selective impairments of executive function were evident. Early dysfunction in the prefrontal region may result in severe and chronic social maladjustment despite largely normal cognitive abilities. These findings can help inform neuropsychological evaluation of patients with possible prefrontal dysfunction in the setting of developmental disabilities or early brain trauma.     

Severe disturbance of higher cognition after bilateral frontal lobe ablation: patient EVR

After bilateral ablation of orbital and lower mesial frontal cortices, a patient had profound changes of behavior that have remained stable for 8 years. Although he could not meet personal and professional responsibilities, his "measurable" intelligence was superior, and he was therefore considered a "malingerer." Neurologic and neuropsychological examinations were otherwise intact. CT, MRI, and SPET revealed a localized lesion of the orbital and lower mesial frontal cortices. All other cerebral areas had normal structure and radioactivity patterns. Such impairments of motivation and complex social behavior were not seen in control cases with superior mesial or dorsolateral frontal lesions.     

Global aphasia without hemiparesis

Three patients acutely developed global aphasia, but did not manifest the typical accompanying right hemiparesis. Computed tomography and magnetic resonance imaging studies demonstrated that the patients had two discrete left hemisphere lesions, one in the anterior language cortices or language-related subcortical areas, and one in the posterior language cortices. Cerebral angiography showed that two patients had complete occlusion of the left internal carotid artery, and the third had an intraluminal "clot" in the supraclinoid portion of the left internal carotid, findings suggestive of an embolic etiology. Our cases indicate that global aphasia without hemiparesis predicts two discrete lesions and a particularly good recovery of speech and language.     

Preserved motor learning in Alzheimer's disease: implications for anatomy and behavior

Learning and retention of 3 types of information were examined in patients with Alzheimer's disease (AD) and in normal controls. While patients were unable to learn series of frequent words and unfamiliar faces, they improved significantly in a motor skill, showing a learning curve similar to controls. Furthermore, no significant loss of the motor skill was evident in a 20 min delay trial. Such dissociation in learning has not been noted previously in AD, although it has been noted in amnesias caused by other disease processes. The results support the existence of two, relatively independent, learning systems related to "declarative" knowledge and "procedural" knowledge. Judging from the pathologic correlates of these amnesias, the declarative knowledge system appears to be associated with corticotemporo/limbic structures, while the procedural system is likely to depend on corticocerebellar/striatal structures. The data also offer additional cognitive correlates for the selective damage to neural systems recently identified in AD.     

Human cerebral asymmetries evaluated by computed tomography.

The handedness of seventy-five persons without evidence of neurological disease, was assessed with a standardised test. An analysis of the CT scans of the same persons was performed to determine (1) presence and lateralisation of frontal and occipital "petalia," (2) width of frontal and occipital lobes of each hemisphere, (3) direction of straight sinus deviation. Results suggest that handedness and cerebral asymmetries are independent variables. There were no significant differences between right-handers and non-right-handers. Also there were no significant differences between strongly left-handed and ambidextrous individuals, nor were there differences between right-handers with or without family history of left-handedness. Irrespective of handedness, left occipital "petalia" was more common than right (p < 0.01), right frontal petalia was more common than left (p < 0.01), and straight sinus deviation was more commonly toward the right. The study does not support the concept that cerebral "symmetry" or "reverse asymmetry" are associated with left-handedness or ambidexterity. The noted asymmetries are more likely to be direct correlates of cerebral language dominance, than of handedness. Furthermore, the possibility that outside forces acting on the bone contributes to the asymmetries cannot be excluded. CT scan may be of value as a direct predictor of cerebral dominance.     

The topographical and neuroanatomical distribution of neurofibrillary tangles and neuritic plaques in the cerebral cortex of patients with Alzheimer's disease.

The distribution of neurofibrillary tangles (NFTs) and neuritic plaques (NPs) was mapped in 39 cortical areas of 11 brains of patients with Alzheimer's disease (AD). Whole hemisphere blocks were embedded in polyethylene glycol (Carbowax), sectioned coronally, and stained with thioflavin S and thionin. The densities of NFTs and NPs were assessed using a numerical rating scale for each area. Scores were grouped by type of cortex and by lobe for statistical analysis. Highly significant differences were obtained. For example, limbic periallocortex and allocortex had more NFTs than any other type of cortex. In descending order, the density of NFTs was as follows: periallocortex (area 28) greater than allocortex (subiculum/CA1 zones of hippocampal formation, area 51) greater than corticoid areas (accessory basal nucleus of amygdala, nucleus basalis of Meynert) greater than proisocortex (areas 11, 12, 24, 23, anterior insula, 38, 35) greater than nonprimary association cortex (32, 46, superior temporal sulcus, 40, 39, posterior parahippocampal cortex, 37, 36) greater than primary sensory association cortex (7, 18, 19, 22, 21, 20) greater than agranular cortex (44-5, 8, 6, 4) greater than primary sensory cortex (41-2, 3-1-2, 17). The laminar distribution of NFTs tended to be selective, involving primarily layers III and V of association areas and layers II and IV of limbic periallocortex. There were far more NFTs in both limbic and temporal lobes than in frontal, parietal, and occipital lobes. In general, NPs were more evenly distributed throughout the cortex, with the exceptions of limbic periallocortex and allocortex, which had notably fewer NPs than other cortical areas. Temporal and occipital lobes had the highest NP densities, limbic and frontal lobes had the lowest, and parietal lobe was intermediate. No significant left-right hemispheric differences for NFT or NP densities were found across the population, and there was no relationship between duration of illness and densities of NFTs or NPs. The regional and laminar distribution of NFTs (and, to a lesser degree, that of NPs) suggests a consistent pattern of vulnerability within the cerebral cortices that seems correlated to the hierarchies of cortico-cortical connections. The higher-order association cortices, especially those in the anterior and ventromedial sectors of temporal lobe, are the most vulnerable, while other cortices appear less vulnerable to a degree commensurate with their connectional "distance" (i.e., synapses removed) from the limbic areas.     

"Paradoxic" ear extinction in dichotic listening: possible anatomic significance

"Paradoxic" extinction in dichotic listening tasks has been attributed to lesions in the interhemispheric auditory pathways, the anatomic courses of which are unknown. The localization of cerebral lesions related to abnormal patterns of dichotic listening was studied in computerized tomographic (CT) scans with a method of anatomic templates. Paradoxic extinction was found consistently with lesions near the lateral wall of the lateral ventricles at the level of the trigone in both left and right hemispheres. On the basis of these findings, we propose that the pathway leaves the auditory cortex traveling backward and upward to arch around the lateral ventricles and join the callosum in its posterior region.     

Impairment of hand movements under visual guidance

Impairment of object-bound movements of the hand performed under visual guidance ("optic ataxia") was a prominent sign in a patient with bilateral circumscribed infarctions in the posterior watershed territory. The sign was interpreted as resulting from defective integration of panoramic visual information with proprioceptive information concerning the upper extremity, and as being related either to damage of structures in the parietooccipital junction or their neural outflow to the premotor region.