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PubMed1976

Metabolic anatomy of focal motor seizures.

Contralateral focal seizures occurred in rats following the intracortical injection of penicillin into the anterior motor cortex. The anatomic dimensions of the metabolic response in the focus as well as the spread of increased activity through the brain were studied by autoradiography following intravenous injection of carbon 14-labeled 2-deoxyglucose. Injections of 25 to 200 units of penicillin resulted in mild to severe contralateral motor jerks coincident with repetitive single spike discharges on the electroencephalogram. Concurrent autoradiography revealed a 1.3- to 2.5-fold increase in metabolic activity in discrete areas in ipsilateral cortex, basal ganglia, thalamus, and contralateral cerebellum. Intracortical injections of over 300 units resulted in the development of recurrent contralateral tonic-clonic seizures, with 20% becoming bilateral. In brains of these animals there was activation of bilateral medial frontal cortex, bilateral extrapyramidal system, thalamus, cerebellum, and limbic structures.

Amygdala↗
PubMed1988

Cerebrospinal fluid somatostatin and neuropeptide Y. Concentrations in aging and in dementia of the Alzheimer type with and without extrapyramidal signs.

Cerebrospinal fluid somatostatin and neuropeptide Y concentrations were measured in 26 healthy normal subjects, 27 patients with dementia of the Alzheimer type (DAT), and seven patients with DAT with extrapyramidal signs (EDAT). In healthy normal subjects, there was no significant correlation between age and either somatostatin or neuropeptide Y concentration. However, the concentrations of both peptides correlated significantly with each other. In patients with DAT and EDAT, the concentrations of somatostatin (17.5 +/- 5.0 and 16.4 +/- 5.0 pg/mL, respectively) were significantly reduced relative to age-matched control subjects (23.1 +/- 8.2 pg/mL) but were unrelated to dementia severity and did not change significantly during the progression of the disease. Neuropeptide Y concentrations did not differ significantly between the age-matched control, DAT, and EDAT groups (38.2 +/- 12.8, 37.0 +/- 12.3, and 30.3 +/- 7.8 pg/mL, respectively). These results suggest that in DAT, dysfunction of cortical somatostatin but not neuropeptide Y transmitter systems is reflected by reduced cerebrospinal fluid concentrations.

Adult↗
PubMed1993

Extrapyramidal signs and other neurologic findings in clinically diagnosed Alzheimer's disease. A community-based study.

The association between findings on the neurologic examination and the clinical diagnosis of Alzheimer's disease was investigated among 467 individuals from a geographically defined community population. Participants were selected by stratified random sampling based on their memory performance in a population survey of community residents 65 years of age and older. Each participant underwent a structured medical, psychiatric, neurologic, and neuropsychologic examination. Of the 467 persons examined there were 134 cases of probable Alzheimer's disease and 167 control subjects. Multiple logistic regression analysis was used to estimate the degree to which the presence of each of several neurologic examination findings affected the age- and sex-adjusted relative odds of having clinically diagnosed Alzheimer's disease. The most striking associations with the diagnosis of Alzheimer's disease were seen with various measures of extrapyramidal dysfunction. These increased relative odds were not markedly affected by excluding from the analysis cases with severe cognitive impairment. The results suggest that involvement of the extrapyramidal system is a common finding in Alzheimer's disease.

Aged↗
PubMed1996

Modeling the influence of extrapyramidal signs on the progression of Alzheimer disease.

OBJECTIVE: To determine how the advent of extrapyramidal signs influences the progression of Alzheimer disease as measured by standard clinical measures. DESIGN: We applied growth curve models to prospective data to characterize patients' cognitive and functional changes over time. To detect changes in disease course related to extrapyramidal signs, their onset was treated as a time-dependent covariate. SETTING: Three research medical centers. PARTICIPANTS: Patients (n = 217) with probable Alzheimer disease. INTERVENTION: Patients were followed up semiannually for 5 years. MAIN OUTCOME MEASURES: Scores on the modified Mini-Mental State Examination and measures of basic and instrumental activities of daily living from the Blessed Dementia Rating Scale. RESULTS: For basic and instrumental activities of daily living, disease course was more rapid once extrapyramidal signs developed. Decline in the modified Mini-Mental State Examination score was greater at the time the signs developed, but not at subsequent visits. CONCLUSIONS: The point at which extrapyramidal signs emerge is associated with measurable acceleration in the progression of Alzheimer disease. This may in part explain why extrapyramidal signs are associated with a poorer prognosis. The differential influence of extrapyramidal signs on cognitive and functional measures suggests that the pathological changes underlying these disease features may vary.

Aged↗
PubMed1979

Improvement in tardive dyskinesia after muscimol therapy.

Muscimol, thought to be a agonist of gamma-aminobutyric acid (GABA), was administered to eight neuroleptic-free subjects with tardive dyskinesia. At oral dose levels from 5 to 9 mg, involuntary movements were consistently attenuated, usually in the absence of sedation. These results support the view that pharmacologic attempts to stimulate GABA-mediated synaptic transmission may afford symptomatic relief to patients with tardive dyskinesia.

Adult↗
PubMed1979

Relationship between the B-mitten EEG pattern and tardive dyskinesia. A pilot control study.

The identification of patients at high risk for the development of tardive dyskinesia (TD) is a major problem in psychopharmacology. We found a possible relationship between the subcortical B-mitten EEG pattern and TD. Twenty-one TD pateints were matched on a number of relevant variables with 21 patients without TD. Ninety-five percent of the TD patients had mittens, compared to 33.3% of controls. The results suggest that the mitten dysrhythmia may be a risk factor for the development of TD. Additional findings suggest that among TD patients, mittens are differentially more frequent in younger (93.1%) as opposed to older (0.0%) subjects.

Adolescent↗
PubMed1992

Limbic system abnormalities identified in schizophrenia using positron emission tomography with fluorodeoxyglucose and neocortical alterations with deficit syndrome.

A hypothesis of psychosis localization in schizophrenia was derived from studying metabolic alterations in rat brain in response to phencyclidine hydrochloride administration. Since phencyclidine and its selective agonist dizocilpine maleate (MK801) induced overlapping and long-lasting metabolic alterations predominantly in limbic areas, the hypothesis developed that schizophrenic patients with psychosis would evidence functional abnormalities in limbic circuits compared with normal controls. Accordingly, 12 actively psychotic, drug-free patients with schizophrenia and matched normal controls underwent functional brain scans using positron emission tomography and fluorodeoxyglucose. Regions of interest were identified on five matched axial slices in each patient and control subject, and average metabolic rates were calculated. Patients with schizophrenia showed a significantly lower regional cerebral metabolic rate of glucose in the hippocampus and the anterior cingulate cortex than did normal controls, but not in neocortical areas or in the extrapyramidal system. When the group of schizophrenic patients was divided into deficit and nondeficit types, a preliminary exploratory analysis suggested thalamic, frontal, and parietal cortical hypometabolism in the deficit subgroup, with normal metabolism in the nondeficit patient group in those areas; in contrast, hippocampal and anterior cingulate cortical metabolism was reduced in both deficit and nondeficit subtypes. These results suggest that the limbic system, especially the hippocampus, is functionally involved in schizophrenic psychosis and that different manifestations of schizophrenia may involve different neuronal circuits.

Adolescent↗
PubMed2000

No relationship between Taq1 a polymorphism of dopamine D(2) receptor gene and extrapyramidal adverse effects of selective dopamine D(2) antagonists, bromperidol, and nemonapride in schizophrenia: a preliminary study.

The relationship between Taq1 A polymorphism of dopamine D(2) receptor (DRD(2)) gene and extrapyramidal adverse effects of bromperidol and nemonapride, which are both antipsychotic drugs with selective and potent DRD(2) antagonistic property, was investigated in Japanese schizophrenic inpatients. Twenty-seven patients were treated with bromperidol at 6 or 12 or 18 mg/day, while 25 patients were treated with nemonapride at 18 mg/day. The duration of treatment was 3 weeks. The A1 and A2 alleles were determined by PCR. The extrapyramidal adverse effects were assessed by the Udvalg for Kliniske Unders¿ogelser side effects rating scale. Six patients were homozygous for the A1 allele, 27 were heterozygous for the A1 and A2 alleles, and 19 were homozygous for the A2 allele. There were no significant differences in the incidences or severity of extrapyramidal adverse effects between the patients with one or two A1 alleles and those with no A1 allele. The present study suggests that Taq1 A polymorphism is not related to the development of extrapyramidal adverse effects during acute phase of bromperidol and nemonapride treatments.

Acute Disease↗
PubMed1999

Visuomotor performance in patients with essential tremor.

Essential tremor (ET) is the most prevalent extrapyramidal disorder, yet its diagnosis is still controversial. This article introduces new findings that pertain to this diagnostic problem. Twenty-three patients with ET were studied. Patients with parkinsonism, cerebellar signs, severe head injury, or those under neuroleptic medication were excluded. Twenty-five normal subjects served as control subjects. Visuomotor tests involving tracking and tracing along three different paths with both the right and left hands, were used. Performance was assessed by measuring test duration, directional error, the proportion of the cumulative test time during which directional error exceeded half the maximal possible level (PT50%), the mean distance from the model path, the velocity of the hand movement, and the number of tracking interruptions. In 15 of 23 patients performance was the same as in the control subjects. These patients were defined as having a "simple condition" of ET (ETs). Considerable visuomotor impairment was found in eight patients who were regarded as having a "complex condition" of ET (ETc). Patients with ETc had significantly lower tracking speed, more tracking interruptions, longer test duration, greater directional error, greater PT50%, and greater distance from path than patients with ETs or control subjects. Most patients with ET appear to have normal visuomotor capabilities (ETs) but some display significant visuomotor disturbances (ETc). Considering the presence of similar impairments in patients with early Parkinson's disease and the increased prevalence of parkinsonism in patients with ET, it is possible that preclinical parkinsonism exists in patients with ETc. Further follow up of patients with ETc is necessary to verify this possibility.

Disease Progression↗
PubMed1984

Afferent and efferent relationships of the basal ganglia.

A survey of the known circuitry of the basal ganglia leads to the following conclusions. (1) No complete account can yet be given of the neural pathways by which the basal ganglia affect the bulbospinal motor apparatus. Channels of exit from the basal ganglia originate from the internal pallidal segment, the pars reticulata of the substantia nigra, and the subthalamic nucleus, and each of these is directed in part rostrally to the cerebral cortex by way of the thalamus, in part caudally to the midbrain. The postsynaptic extension of the mesencephalic channels to bulbar and spinal motor neurons is largely unknown. Since the ascending channels are collectively of greatest volume, the notion remains plausible that the basal ganglia act in considerable part by modulating motor mechanisms of the cortex. (2) Recent findings in the rat suggest that the striatum is subdivided into a ventromedial, limbic system-afferented region and a dorsolateral, 'non-limbic' region largely corresponding to the main distribution of corticostriatal fibres from the motor cortex. These two subdivisions appear to give rise to different striatofugal lines, the outflow from the limbic-afferented sector partly re-entering the circuitry of the limbic system. (3) The limbic-afferented striatal sector suggests itself as an interface between the motivational and the more strictly motor aspects of movement. This suggestion is strengthened by evidence that the 'limbic striatum' seems enabled by its striatonigral efferents to modulate not only the source of its own dopamine innervation but also that of a large additional striatal region.

Animals↗