Deep brain stimulation of the ventral internal capsule/ventral striatum for obsessive-compulsive disorder: worldwide experience.

Psychiatric neurosurgery teams in the United States and Europe have studied deep brain stimulation (DBS) of the ventral anterior limb of the internal capsule and adjacent ventral striatum (VC/VS) for severe and highly treatment-resistant obsessive-compulsive disorder. Four groups have collaborated most closely, in small-scale studies, over the past 8 years. First to begin was Leuven/Antwerp, followed by Butler Hospital/Brown Medical School, the Cleveland Clinic and most recently the University of Florida. These centers used comparable patient selection criteria and surgical targeting. Targeting, but not selection, evolved during this period. Here, we present combined long-term results of those studies, which reveal clinically significant symptom reductions and functional improvement in about two-thirds of patients. DBS was well tolerated overall and adverse effects were overwhelmingly transient. Results generally improved for patients implanted more recently, suggesting a 'learning curve' both within and across centers. This is well known from the development of DBS for movement disorders. The main factor accounting for these gains appears to be the refinement of the implantation site. Initially, an anterior-posterior location based on anterior capsulotomy lesions was used. In an attempt to improve results, more posterior sites were investigated resulting in the current target, at the junction of the anterior capsule, anterior commissure and posterior ventral striatum. Clinical results suggest that neural networks relevant to therapeutic improvement might be modulated more effectively at a more posterior target. Taken together, these data show that the procedure can be successfully implemented by dedicated interdisciplinary teams, and support its therapeutic promise.

The impact of behavioral symptoms on activities of daily living in patients with dementia.

The authors examined whether scores on two recently developed measures of behavioral disturbance, the Frontal Lobe Personality Scale (FLOPS) and the Neuropsychiatric Inventory (NPI), are associated with functional impairments in patients with dementia. Caregivers of 30 dementia patients were administered the FLOPS Family Form, the NPI, and an Activities of Daily Living (ADL) scale. Findings indicated a relationship between behavioral changes and functional limitations in patients with dementia. Moreover, the FLOPS, an instrument designed to specifically measure behaviors subserved by frontal lobe systems, was more strongly related to failures in instrumental ADLs than was the NPI. The authors conclude that behavioral measures add information over and above that available from cognitive tests in determining ADL functioning.

Prediction of functional status from neuropsychological tests in community-dwelling elderly individuals.

Age-related dysfunction of frontal systems can result in deficits in planning, organization, self-control, and awareness of problems, which are likely to affect the ability to care for one's self. The purpose of this study was to determine the relationship between age-related frontal/executive deficits and impairment in instrumental activities of daily living (IADLs) in elderly individuals. Twenty-seven community-dwelling individuals were administered a comprehensive battery of neuropsychological tests and a performance-based evaluation of IADLs. Multiple regression analyses indicated that executive function and depression severity accounted for a significant proportion of variance in IADLs, with executive function making the greatest contribution. Tests measuring other cognitive functions, such as memory, language, and spatial skills, did not contribute significantly to the prediction of functional status. Furthermore, executive measures accounted for more variance than other demographic characteristics such as general health status, age, and educational level. The results of this study indicate that executive dysfunction in normal aging may be the best predictor of functional decline. A better understanding of the mechanisms that underlie IADL skills will ultimately aid in the development of compensatory and intervention strategies designed to delay the onset of assisted living and nursing home placement.

Neuropsychological and magnetic resonance imaging abnormalities associated with a plasmacytoma of the frontal dura: a case report.

OBJECTIVE: The goal of this investigation was to describe the neuropsychological and magnetic resonance imaging (MRI) findings in a patient with an extramedullary plasmacytoma that extensively infiltrated the cerebral dura, especially over the frontal region. BACKGROUND: Extramedullary plasmacytomas are rare tumors that have been reported to involve the dura matter in only a small number of cases. In most of the reported occurrences, the dura plasmacytomas were successfully treated with a combination of surgery and irradiation, without prominent cognitive sequelae. METHOD: MRI of the brain and neuropsychological tests were conducted approximately 13 months after the patient underwent radiotherapy. In addition, measures of frontal lobe personality characteristics were obtained before and after radiotherapy. RESULTS: MRI findings revealed extensive enhancement around the anterior frontal lobes and prominent involvement of the anterior longitudinal fissure. Results from neuropsychological testing indicated mild to moderately impaired performance on tests of working memory, complex attention, and cognitive flexibility. Further, the patient reported experiencing personality changes consistent with frontal lobe dysfunction as part of the initial symptoms of the disease, which remained unchanged after treatment. CONCLUSIONS: Our findings are the first to describe cognitive sequelae of dural plasmacytomas. In addition, results from this case study reveal that plasmacytomas of the frontal dura produce personality changes similar to those observed in patients with significant frontal lobe injury. Finally, plasmacytomas that significantly infiltrate the frontal lobes may be insensitive to radiotherapy and result in residual cognitive and personality abnormalities.

Assessing frontal lobe behavioral syndromes with the frontal lobe personality scale.

Reliability and construct validity are reported for the Frontal Lobe Personality Scale (FLOPS), a brief neurobehavior rating scale. The FLOPS Family form was completed by family members of 24 frontal lobe brain-damaged patients, 15 non-frontal lobe brain- damaged patients, and 48 healthy controls. Intrascale reliability was demonstrated (internal consistency.96; split half.93). Validity studies of frontal lobe patients post-lesion compared to their pre-lesion status, to healthy controls, and of frontal lobe patients pre- and post-lesion compared to non-frontal lobe patients pre- and post-lesion, indicated that frontal lobe patients post-lesion showed significantly more frontal behavior than (a) pre-lesion frontal lobe patients, (b) healthy controls, and (c) post-lesion non-frontal lobe patients. The FLOPS appears to be useful for quantifying frontal lobe behavior in clinical and research settings.

The clinician-scientist in neuropsychiatry: a position statement from the Committee on Research of the American Neuropsychiatric Association.

Neuropsychiatric research seeks to improve the lives of patients with brain-based behavioral disturbances. There has been dramatic progress in diagnosis and treatment of neuropsychiatric disorders, and progress in neuroscience and biotechnology promises further success. Paradoxically, recent trends threaten to erode this progress. In this environment, neuropsychiatric clinician-scientists must advocate for the importance of research. This position statement defines neuropsychiatric research, describes current challenges to the neuropsychiatric clinician-scientist, summarizes research opportunities, describes how future neuropsychiatric clinician-investigators should be trained, and makes recommendations for promoting neuropsychiatric research.

Reduplicative paramnesia: longitudinal neurobehavioral and neuroimaging analysis.

Reduplicative paramnesia (RP) is a delusion in which the patient perceives familiar places, objects, or events to have been duplicated. The current case describes the development of RP in an 81-year-old male following a large right frontal lobe infarction. As the patient had been hospitalized previously with hemorrhagic contusions, neurologic, neuropsychological, and neuroimaging data were obtained both prior to and following RP onset. Psychophysiologic data were obtained following the development of the delusion. Both premorbidly and at follow-up, neuropsychological functioning was characterized by significant impairments of learning and memory and frontal-executive functions. Language and visuospatial skills and motor speed were intact both before and after RP onset. The case is described within the context of preexisting theories of RP, and it is surmised that the delusion is secondary to temporal-limbic-frontal dysfunction giving rise to a distorted sense of familiarity and impaired ability to resolve the delusion via reasoning.

Neuropsychiatric factors in the illusion of visitors among geriatric patients: a case series.

The 'illusion of visitors' is a common phenomenon among geriatric patients presenting for psychiatric or neurologic evaluation and treatment. Although these illusory beliefs are etiologically diverse, patients may commonly have visual impairment and functional and/or structural disruption of frontal and right-hemisphere-mediated cognitive functioning. This article outlines eight cases of illusory beliefs among elderly patients, presenting psychiatric, neurologic, neuroimaging, and neuropsychological findings among these patients. Commonalities and differences among these cases are discussed, and a framework is provided for multidisciplinary assessment and treatment of patients presenting with illusory beliefs.

Cognitive screening instruments in neuropsychiatry: a report of the Committee on Research of the American Neuropsychiatric Association.

A 1994 survey by the Research Committee of the American Neuropsychiatric Association revealed that 58% of respondents employed formal assessment of cognitive status; the Mini-Mental State Examination (MMSE) and neuropsychological testing were the commonest techniques. Literature review on common cognitive screening instruments found that the MMSE has widespread popularity, ease of use, and a large body of research demonstrating its sensitivity to common neuropsychiatric disorders. The Committee recommends that clinicians who employ the MMSE 1) use it as a minimum screening for cognitive dysfunction; 2) employ age- and education-normative corrections; and 3) supplement it with specific measures of spatial functions, delayed memory, and executive abilities. The Modified MMSE and the Neurobehavioral Cognitive Status Examination also show promise as screening tools.

Subcortical hyperintensities on MRI and activities of daily living in geriatric depression.

Data from 30 elderly inpatients with major depression were analyzed to explore the relationship between subcortical hyperintensities (SH) on MRI and activities of daily living (ADLs). A comparison of subjects based on a median split of the severity of SH revealed that subjects with greater SH performed worse on both instrumental and physical ADLs. A hierarchical multiple regression revealed that age, depression severity, neuropsychological test performance, and SH variables accounted for a total of 53% of the variance in ADL functioning. Severity of SH accounted for an additional 18% of the variance over and above the other three variables. Results suggest that severity of subcortical disease measured by MRI improves prediction of functional impairment in elderly individuals.

Laterality differences in quantitative and qualitative Hooper performance.

The Hooper Visual Organization Test (HVOT) is a measure of visuospatial processing commonly employed in neuropsychological assessment. Despite the well-documented relationship between visuospatial abilities and right hemisphere function, the literature has not supported a right hemisphere association with HVOT performance. The current study was conducted to examine laterality differences in HVOT performance. Sixty-seven geriatric stroke patients (44 right CVAs, 23 left CVAs) were administered the HVOT and the Mini-Mental State Exam (MMS). Results revealed significant differences between CVA groups for total score, with right CVA patients performing more poorly. Qualitative error analyses revealed highest frequencies for part responses and don't know/no response errors. Between-group differences were seen for part and unformed/unassociated errors (higher right CVA rates), and language-based errors (higher left CVA rates). Findings are consistent with theories of brain lateralization and suggest that whereas HVOT performance predominantly involves right hemisphere functions, left hemisphere dysfunction may also lead to impaired performance, and the two can be discriminated by qualitative analysis of errors.

Predictors of neuropsychological impairment in alcoholics: antisocial versus nonantisocial subtypes.

The role of demographic, perinatal/developmental, and acquired subject characteristics in determining neuropsychological (NP) performance was investigated in 22 alcoholics with Antisocial Personality Disorder (ASPD) and 84 non-ASPD alcoholics. Results of stepwise multiple regression analyses revealed that in ASPD subjects, poor NP performance was predicted by less education, childhood symptoms of Conduct Disorder, drinks per drinking day, and history of head injury, accounting for 80% of the explained variance (p < .0001). In non-ASPD subjects, NP performance was predicted by self-reported history of diagnosed Attention Deficit Disorder, Verbal Learning Disability, and symptoms of Nonverbal Learning Disability, accounting for 24% of the explained variance (p < .0001). These results suggest the presence of potentially different lifelong paths to NP impairment among ASPD and non-ASPD alcoholics. Further exploration of the multivariate predictors of neuropsychological performance in subgroups of alcoholics is warranted.

Efficacy of buspirone in the treatment of posttraumatic stress disorder: an open trial.

Although numerous psychotropic medications have a reported efficacy in posttraumatic stress disorder (PTSD), treatment of the condition remains largely empirical. The animal model of inescapable stress (IS) produces many physiological changes similar to PTSD in humans. The azapirones (e.g., buspirone, gepirone) are effective in alleviating the signs of IS in animals and should theoretically be effective in alleviating the symptoms of PTSD in humans. An open trial of buspirone in 8 patients meeting DSM-III-R criteria for posttraumatic stress disorder was conducted. Measurement tools included the Structured Interview for PTSD (SI-PTSD), Impact of Life Events Scale (ILES), and Beck Depression Inventory (BDI). Seven out of 8 patients exhibited a significant reduction in symptoms as measured by the SI-PTSD and BDI. The response was less significant on the ILES. Buspirone may be effective in alleviating the symptoms of PTSD. Further clinical trials to confirm this apparent efficacy appear warranted.

Assessment of frontal lobe functions.

The authors describe methods for conducting a thorough assessment of functions subserved by the frontal lobes, employing both bedside and psychometric methods of assessing frontal subsystems. Qualitative or process aspects of frontal behavior observable from formal testing, interview, and social behavior are noted. It is argued that the skilled clinician must be guided by a knowledge of frontal lobe subsystems and their roles in determining specific types of abnormal behavior. The clinician will then be alert to changes in incidental behaviors that indicate frontal impairment, and bedside maneuvers can be designed to discriminate dysfunction. Given the complexity of the behaviors involved and the profound effects of maturation and aging on frontal functions, neuropsychological assessment can provide an invaluable tool for testing these functions.

The frontal lobes and content-specific delusions.

Contemporary research has shown that delusions are often the product of identifiable neurologic disease, particularly when the delusions have a specific theme or are confined to one topic--monosymptomatic or content-specific delusions. Although these delusions are considered rare, some of them can be found at high rates in certain populations and settings. The literature on several classes of content-specific delusions (misidentification, sexual, and somatic) is critically reviewed. The review demonstrates that when adequate diagnostic workups are conducted, a high proportion of such delusions are found to have a neurologic basis. Lesions of the frontal lobes and the right hemisphere are shown to be critical to the development and persistence of many content-specific delusions.

The ability of the Dementia Rating Scale to predict everyday functioning.

The Dementia Rating Scale (DRS) is a brief neuropsychological assessment battery designed to assess five areas of cognitive functioning in the elderly. The relationship between DRS performance and everyday functioning was examined for 50 psychogeriatric patients. Everyday functioning was assessed with a standardized performance measure examining self-care, safety, money management, cooking, medication administration, and community utilization. Regression analyses were conducted for each of the six functional domains. In addition, correlations between the DRS subscales and the functional areas were computed. Results revealed significant predictive relationships (p <.01) between performance on the DRS and most functional domains. The multiple Rs ranged from .52 - .70, accounting for 27% to 49% of the variance. The Initiation/Perseveration subscale was most heavily weighted in each analysis. Significant correlations were obtained between subdomains of cognition and most functional areas. The findings provide evidence of relationships between DRS performance and functional ability.

Alcohol, head injury, and neuropsychological function.

Evidence is reviewed indicating that the extent of alcohol abuse alone cannot account for the neuropsychological deficits observed in alcoholics, and that alcohol abuse and head injury may interact in some patients to influence neuropsychological status. Alcohol abuse both increases the risk for head trauma and potentiates the resulting brain injury, which can lead to negative neuropsychological consequences. Clinicians involved in the treatment of addiction should assess patients for history of head injury, and neuropsychological deficits consequent to both head injury and ethanol. These deficits may limit patient ability to comply with addiction rehabilitation programs. Conversely, clinicians in acute care and rehabilitation of the sequelae of head trauma should routinely assess their patients for substance abuse, because such abuse can have a significant impact on recovery from brain injury.

Othello syndrome secondary to right cerebrovascular infarction.

The Othello syndrome, or delusional jealousy, occurs in idiopathic psychoses and in neurodegenerative diseases, but has rarely been described in patients with cerebrovascular infarction. A patient was observed to exhibit the delusion shortly after cerebral ischemic injury in the absence of other psychiatric symptoms. The underlying pathology was consistent with recent reports on content-specific delusions, implicating right hemisphere and frontal lobe involvement in the misinterpretation and misidentification of complex information. Psychological factors were hypothesized to shape the content of the delusional misinterpretations.

Liver function tests and neuropsychologic impairment in substance abusers.

The relationship between residual neuropsychologic dysfunction in alcoholics and subtle changes in liver function during acute phases of treatment was examined. Noncirrhotic alcoholics who exhibited extreme elevations in the liver enzyme gamma-glutamyl transferase (GGT) were found to have greater impairments in tasks of visuoperceptual and conceptual abilities when compared to alcoholics with normal or only mild elevations in GGT. The relationship between acute liver dysfunction and residual neuropsychologic impairment appeared to be independent of age and patterns of drinking. The implications of these findings in relation to treatment planning and prognosis of alcoholics are discussed.

Psychiatric presentations of intracranial cysts.

Eight patients with intracranial cysts presenting with primary psychiatric diagnoses were studied. The cysts were visible on computed tomography (CT) and magnetic resonance imaging (MRI), and they produced neurologic, electroencephalographic (EEG), and neuropsychologic abnormalities. Descriptions of psychiatric manifestations associated with intracranial cysts are rare, and their potential neuropsychiatric significance has been minimized. This study demonstrates that intracranial cysts can cause neuropsychiatric symptoms, that surgical intervention may resolve the psychiatric manifestations in selected cases, and, in cases not warranting surgery, that psychopharmacological therapy to treat the behavioral manifestations is indicated. These cases mandate consideration of intracranial cysts in the diagnostic and therapeutic formulation of atypical neuropsychiatric disorders.