Cerebral metabolic correlates as potential predictors of response to anterior cingulotomy for obsessive compulsive disorder.

BACKGROUND: As interventions for severe, treatment-refractory obsessive compulsive disorder (OCD), neurosurgical procedures are associated with only modest efficacy. The purpose of this study was to identify cerebral metabolic correlates as potential predictors of treatment response to anterior cingulotomy for OCD. METHODS: Clinical data were analyzed in the context of a retrospective design. Subjects were 11 patients who underwent stereotactic anterior cingulotomy for OCD. Symptom severity was measured using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) before and at approximately 6 months postoperative. Preoperative F-18-fluorodeoxyglucose-positron emission tomography (FDG-PET) data were available. Statistical parametric mapping methods were used to identify loci of significant correlation between preoperative regional cerebral metabolism and postoperative reduction in Y-BOCS scores. RESULTS: One locus within right posterior cingulate cortex was identified, where preoperative metabolism was significantly correlated with improvement in OCD symptom severity following cingulotomy. Specifically, higher preoperative rates of metabolism at that locus were associated with better postoperative outcome. CONCLUSIONS: A possible predictor of treatment response was identified for patients with OCD undergoing anterior cingulotomy. Further research, utilizing a prospective design, is indicated to determine the validity and reliability of this finding. If confirmed, an index for noninvasively predicting response to cingulotomy for OCD would be of great value.

Behavioral manifestations of central pontine myelinolysis.

A young woman with a clinical history and magnetic resonance imaging scan consistent with central pontine myelinolysis came to medical attention because of prominent behavioral symptoms. Marked clinical recovery occurred despite persistent radiologic abnormalities. Rapid correction of hyponatremia was probably related to the development of the central pontine myelinolysis. A normal computed tomographic scan and the absence of brain-stem signs delayed accurate diagnosis.

Neuropsychological patterns and language deficits in 20 consecutive cases of autopsy-confirmed Alzheimer's disease.

A retrospective chart review of clinical symptoms was done for 20 consecutive patients in whom postmortem examination had revealed senile plaques and neurofibrillary tangles in a distribution consistent with Alzheimer's disease. All patients had met clinical diagnostic criteria for probable Alzheimer's disease. On initial examination, 1 to 14 years beyond putative onset of the dementia, all patients displayed at least some memory impairment. In 16 patients, disturbances of attention or recent memory were among the most salient features. In two patients, language disturbances, and in two others, visuospatial deficits, were more prominent than difficulties with memory and attention. On initial examination, 17 of the 20 patients displayed word-finding difficulties, characteristically in the context of a fluent, anomic aphasia. All of the 12 reexamined patients demonstrated progressive, although variable, deterioration. In general, the initial salient deficit remained salient during much of the disease course. Language comprehension was spared in the earlier stages but eventually deteriorated. Severe deficits emerged in all major cognitive domains as the disease reached the terminal stages. Nonfluent aphasias (eg, Broca's aphasia) were not observed even in the advanced stages of the disease.

Deficits in visual cognition and attention following bilateral anterior cingulotomy.

A series of eight tests of visual cognitive abilities was used to examine pre- to post-operative performance changes in a patient receiving bilateral anterior cingulotomy. Compared with a set of eight matched control participants, post-operatively, the patient exhibited deficits in (a) the ability to sequence novel cognitive operations required to generate multipart images or rotate perceptual stimuli; (b) the ability to search for, select, and compare images of objects when the instructions did not specify precisely which objects should be visualized; and, (c) the ability to select a controlled and unpracticed response over an automatic one. Other imagery and cognitive tasks were not affected. Results are consistent with the hypothesis that anterior cingulate cortex is a component of an executive control system. One of the anterior cingulate's roles may be to monitor on-line processing and signal the motivational significance of current actions or cognitions.

Cardiac manifestations of complex partial seizures.

Six patients with complex partial seizures in whom the first or most prominent manifestation was cardiovascular are described. "Anginal pain," which was usually atypical, developed in five patients (mean age 34), although three were admitted to coronary care units; sinus tachycardia developed in one, sinus bradycardia leading to syncope developed in one, and a cluster of symptoms suggestive of pheochromocytoma developed in one. The causal relationship between complex partial seizures and these symptoms is based on clinical history, electrodiagnostic studies indicating epilepsy (in five of six cases) without changes of myocardial ischemia, and response to anticonvulsant but not antianginal medications. Complex partial seizures that present with cardiovascular and other visceral symptoms represent an underdiagnosed, treatable disorder.

Improvement in severe self-mutilation following limbic leucotomy: a series of 5 consecutive cases.

BACKGROUND: The efficacy of neurosurgical intervention for self-mutilation behavior associated with severe, intractable psychiatric disorders remains undetermined. We report the effects of limbic leucotomy in 5 consecutive patients with severe self-mutilation behaviors. METHOD: After unsolicited referrals from their psychiatrists and careful consideration by the Massachusetts General Hospital Cingulotomy Assessment Committee (MGH-CAC), 5 patients were treated with limbic leucotomy. Their primary DSM-IV psychiatric diagnoses were either obsessive-compulsive disorder or schizoaffective disorder. Comorbid severe, treatment-refractory self-mutilation was an additional target symptom. Outcome was measured by an independent observer using the Clinical Global Improvement. Current Global Psychiatric-Social Status Rating, and DSM-IV Global Assessment of Functioning scales in addition to telephone interviews with patients, families, their psychiatrists, and treatment teams. The mean postoperative follow-up period was 31.5 months. RESULTS: All measures indicated sustained improvement in 4 of 5 patients. In particular, there was a substantial decrease in self-mutilation behaviors. Postoperative complications were transient in nature. and postoperative compared with preoperative neuropsychological assessments revealed no clinically significant deficits. CONCLUSION: In carefully selected patients as described in this report, limbic leucotomy may be an appropriate therapeutic consideration for self-mutilation associated with severe, intractable psychiatric disorders.

Differential laminar distribution of acetylcholinesterase and butyrylcholinesterase containing tangles in the cerebral cortex of Alzheimer's disease.

A sensitive histochemical method for the visualization of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity was used to determine the laminar distribution of cholinesterase-positive cortical tangles in Alzheimer's disease (AD). In many cortical areas AChE- and BChE-positive tangles displayed a completely overlapping distribution. In other areas the most superficial layers contained only AChE-positive tangles whereas the deepest layers contained only BChE-positive tangles. These observations suggest that some cholinesterase-positive tangles have a predominantly (if not exclusively) AChE-like reactivity whereas others have a reactivity that is predominantly BChE-like. The intermingling of AChE- and BChE-positive tangles in most cortical areas and layers suggests that there may also be a third population in which the two enzymes are equally prominent in the same tangle.

Magnetic resonance image-guided stereotactic cingulotomy for intractable psychiatric disease.

We describe the modern operative technique of magnetic resonance (MR) image-guided stereotactic cingulotomy and discuss the indications, results, and complications of this procedure. A retrospective analysis of psychiatric outcome was performed for 34 patients with intractable major affective disorder and/or obsessive-compulsive disorder who underwent MR image-guided stereotactic cingulotomy since 1991. Fourteen patients underwent multiple cingulotomies (50 total procedures). Overall, 38% of the patients were classified as responders, 23% as possible responders, and 38% as nonresponders. Of the patients who did not respond to initial cingulotomies and who underwent multiple cingulotomies, 36% became responders, 36% possible responders, and 28% nonresponders. There were no deaths or long-term side effects related to the procedure. The therapeutic results of MR image-guided stereotactic cingulotomy are similar to the results of earlier methods of cingulotomy, and the use of MR imaging offers substantial technical advantages. This procedure also compares favorably with other neurosurgical procedures performed for intractable psychiatric disease with a low rate of undesired side effects. Cingulotomy is safe and well tolerated, with over one-third of the patients demonstrating significant improvement; however, prospective long-term follow-up studies are needed to further define the role of surgery in treating intractable psychiatric disease.

Volume reduction in the caudate nucleus following stereotactic placement of lesions in the anterior cingulate cortex in humans: a morphometric magnetic resonance imaging study.

OBJECT: The goal of this study was to test hypotheses regarding changes in volume in subcortical structures following anterior cingulotomy. METHODS: Morphometric magnetic resonance (MR) imaging methods were used to assess volume reductions in subcortical regions following anterior cingulate lesioning in nine patients. Magnetic resonance imaging data obtained before and 9 +/- 6 months following anterior cingulotomy were subjected to segmentation and subcortical parcellation. Significant volume reductions were predicted and found bilaterally within the caudate nucleus, but not in the amygdala, thalamus, lenticular nuclei, or hippocampus. Subcortical parcellation revealed that the volume reduction in the caudate nucleus was principally referrable to the body, rather than the head. Furthermore, the magnitude of volume reduction in the caudate body was significantly correlated with total lesion volume. CONCLUSIONS: Taken together, these findings implicate significant connectivity between a region of anterior cingulate cortex (ACC) lesioned during cingulotomy and the caudate body. This unique data set complements published findings in nonhuman primates, and advances our knowledge regarding patterns of cortical-subcortical connectivity involving the ACC in humans. Moreover, these findings indicate changes distant from the site of anterior cingulotomy lesions that may play a role in the clinical response to this neurosurgical procedure.

A magnetic resonance imaging study of regional cortical volumes following stereotactic anterior cingulotomy.

The purpose of this study was to test the hypothesis that orbitofrontal cortical volume would be reduced following anterior cingulotomy for obsessive-compulsive disorder (OCD). Whole brain cortical parcellation was performed on magnetic resonance imaging (MRI) data from nine patients, before and 9 (+/-6) months following anterior cingulotomy. No significant volumetric reductions were found in the orbitofrontal cortex. Exploratory findings of reduced volume in ventral temporo-fusiform and posterior cingulate regions were consistent with chance differences, in the face of multiple comparisons. Therefore, though the circumscribed lesions of anterior cingulotomy have recently been associated with corresponding volumetric reductions in the caudate nucleus, no comparable volumetric reductions are evident in cortical territories. Taken together, these results are most consistent with a model of cingulo-striatal perturbation as a putative mechanism for the efficacy of this procedure. While limitations in sensitivity may have also contributed to these negative findings, the methods employed have previously proven sufficient to detect cortical volumetric abnormalities in OCD. The current results may reflect a relatively diffuse pattern of cortico-cortical connections involving the neurons at the site of cingulotomy lesions. Future functional neuroimaging studies are warranted to assess possible cortical or subcortical metabolic changes associated with anterior cingulotomy, as well as predictors of treatment response.

Diagnostic testing and dementia.

The prevalence of dementia is expected to increase markedly as our population ages. Although only a minority of cases currently are found to have treatable causes, the personal and financial costs of misdiagnosis are great. Furthermore, progress in developing effective therapy hinges on accurate diagnosis. This article reviews the current state of diagnostic testing in the diagnosis of dementia.

Psychiatric manifestations of right hemisphere infarctions.

Five right-handed patients (aged 45 to 78 years) developed acute psychotic disturbances in conjunction with infarcts in the right hemisphere. Their presentation was marked by agitation, inattention, suspiciousness, paranoid delusions, hallucinations, and lack of appropriate concern. Several of these patients initially received primary psychiatric diagnoses. Although neurological findings indicative of right hemisphere involvement could also be elicited, these were generally overshadowed by the more dramatic behavioral alterations. The electroencephalogram and computerized axial tomography were positive in most cases. These cases demonstrate that the possibility of a right hemisphere lesion needs to be entertained in patients who present with an atypical psychotic episode.

Neuropsychiatry of frontal lobe dysfunction in violent and criminal behaviour: a critical review.

OBJECTIVES: To establish the link between frontal lobe dysfunction and violent and criminal behaviour, based on a review of relevant literature. METHODS: Articles relating evidence of frontal lobe dysfunction with violence or crime were collected through a MEDLINE search using the keyword "frontal lobe" combined with the terms "aggression," "violence," "crime," "antisocial personality disorder," "psychopathy," "impulse control disorders", and "episodic dyscontrol." Reference lists were then searched for additional articles. RESULTS: High rates of neuropsychiatric abnormalities reported in persons with violent and criminal behaviour suggest an association between aggressive dyscontrol and brain injury, especially involving the frontal lobes. The studies reviewed support an association between frontal lobe dysfunction and increased aggressive and antisocial behaviour. Focal orbitofrontal injury is specifically associated with increased aggression. Deficits in frontal executive function may increase the likelihood of future aggression, but no study has reliably demonstrated a characteristic pattern of frontal network dysfunction predictive of violent crime. CONCLUSIONS: Clinically significant focal frontal lobe dysfunction is associated with aggressive dyscontrol, but the increased risk of violence seems less than is widely presumed. Evidence is strongest for an association between focal prefrontal damage and an impulsive subtype of aggressive behaviour.

The comportmental learning disabilities of early frontal lobe damage.

Two adult patients are described who suffered bilateral prefrontal damage early in life and who subsequently came to psychiatric attention because of severely aberrant behaviour. A battery of developmental psychology paradigms (not previously used to assess neurologically impaired individuals) showed that social and moral development of these 2 patients was arrested at an immature stage. In comparison with other types of brain damage which disrupt cognitive development, frontal damage acquired early in life appears to provide the neurological substrate for a special type of learning disability in the realms of insight, foresight, social judgement, empathy, and complex reasoning.

Dissociated perceptual-sensory and exploratory-motor neglect.

A patient with a right sided parietal lobe infarction manifested left sided sensory extinction in the visual, auditory, and tactile modalities but had only mild exploratory-motor neglect. In contrast, another patient with a right frontal haemorrhage demonstrated only left sided exploratory-motor hemispatial neglect. Tasks that combined perceptual and exploratory features elicited varying degrees of neglect in each patient. These two cases with dissociated neglect behaviour lend further evidence for behavioural specialisation within components of a cortical network for directed attention: sensory-representational aspects mediated primarily by the parietal component, motor-exploratory primarily by the frontal component. These cases also highlight the need to include and distinguish among several different measures of neglect in the clinical investigation of patients with hemispatial inattention.

Right hemisphere learning disability associated with left hemisphere dysfunction: anomalous dominance and development.

Two patients are described with the social emotional processing disorder, a developmental syndrome usually ascribed to right hemisphere dysfunction. In these two patients however, neurological examinations, EEG, and neuroimaging studies were all consistent with left hemisphere dysfunction. Both patients were left handed and had findings suggestive of anomalous dominance for language. It is proposed that early left hemisphere injury may have resulted in functional reorganisation that allowed sparing of language and motor skills but interfered with the development of functions that the right hemisphere normally subserves.