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PubMed1981

Effect of oxotremorine on local cerebral glucose utilization in motor system regions of the rat brain.

The [14C]2-deoxy-D-glucose technique was used to test the effects of central muscarinic stimulation on local cerebral glucose utilization (LCGU) in rats. Systemic administration of the muscarinic agonist oxotremorine (OXO, 0.7 mg/kg, ip) increased LCGU in brain regions involved in motor function: the sensorimotor cortex; the extrapyramidal motor system, including the striatum, globus pallidus, red nucleus, substantia nigra, subthalamus and ventral nucleus of the thalamus; the cerebellar vermis, fastigial nucleus and nucleus interpositus; and the vestibular nucleus. No effects were observed in the fibers of the pyramidal tract, internal capsule, cerebellar white matter and the dentate nucleus. Increases were not affected by methylatropine (1 mg/kg sc), but were completely antagonized by scopolamine (2.5 mg/kg, ip). The anatomic distribution and magnitude of the LCGU response to OXO were not simply correlated with the reported densities of muscarinic receptors.

Animals↗
PubMed2002

Documentation and evaluation of adverse drug reactions (ADR)--contribution from a poison information center.

The Department of Clinical Pharmacology in Jena is a pharmacovigilance center in a study on intensified spontaneous adverse drug reaction reporting. Physicians specialized in clinical pharmacology screen admissions to the Department of Internal Medicine for possible adverse drug reactions. Because of the collaboration between the Pharmacology Department and the nearby Poison Information Center (PIC) in Erfurt the question occurred whether the latter might contribute to adverse drug reaction monitoring. We compared the ADR registered by the intensified spontaneous reporting system in 1999 with those of the PIC during the same period. Each symptom observed was regarded as 1 case. Every suspected drug was also treated separately. The symptoms were classified using adverse reaction terminology. The drugs were classified according to the WHO Anatomical Therapeutic Chemical (ATC) classification index. The causality assessment was based upon bibliographic data and the method of Bégaud et al. [1985]. Only possible, probable or very probable ADR were compared. The PIC registered mainly psychiatric and nervous system disorders sedation and extrapyramidal disorders were the most frequent reactions - unlike the pharmacovigilance study which registered primarily gastrointestinal and heart rate disorders. The PIC registered mainly drugs used in the therapy of disorders of the central nervous system, i.e. mostly psycholeptics and drugs acting on the alimentary tract, mostly anticholinergics. Drugs for the therapy of sensory organs disorders were frequent owing to the systemic and local adverse drug effects of anticholinergic mydriatics. The PIC and pharmacovigilance centers can benefit from co-operation. The PIC provides easy access to qualified drug information and is thus a useful tool in ADR evaluation. Although the number of adverse reactions assessed was small, their evaluation revealed problems in drug usage which would not otherwise be reported. The evaluation has enlarged the pool of ADR data which is the basis for signal detection.

Adverse Drug Reaction Reporting Systems↗
PubMed1981

Review of a new gastrointestinal drug--metoclopramide.

The pharmacology, pharmacokinetics, therapeutic and diagnostic uses, toxicity, adverse reactions, and contraindications of metoclopramide are reviewed. Metoclopramide enhances the rate of gastric emptying by (1) augmenting esophageal peristalsis, gastric antral contractions, and small intestine transit time and (2) increasing resting pressures of the lower esophageal and pyloric sphincters. The drug does not stimulate gastric acid secretions. The injectable form is approved for use to facilitate intubation of the small intestine and the passage of barium into the intestine for radiographic procedures. Tablets are approved for the treatment of symptoms associated with diabetic gastroparesis. The drug has been used in the treatment of vomiting of various etiologies. The side effects of metoclopramide are usually mild, transient, and reversible with discontinuation of the drug. They include drowsiness, GI disturbances, extrapyramidal reactions, and increased lactation. Metoclopramide should not be given in combination with MAO inhibitors, tricyclic antidepressants, sympathomimetic amines, or to patients with pheochromocytoma, GI hemorrhage, obstruction, or perforation. Metoclopramide appears to be an effective drug in stimulating the mobility of the upper gastrointestinal tract without increasing gastric secretions. Further studies are needed to assess its value in the treatment of vomiting secondary to anesthesia and chemotherapy, and to assess its precise role in the treatment of diabetic gastroparesis.

Diabetes Complications↗
PubMedDate not supplied

[Analysis of functional and biochemical changes in feline cerebral hemispheres after subchronic haloperidol administration].

Feline experiments have revealed that subchronic haloperidol causes asymmetric changes in the mesencephalic levels of dopamine and serotonin and impairs intrahemispheric balance between the dopaminergic and serotoninergic systems. At the same time the neuroleptic increases motor asymmetry, which appears in response to apomorphine, and changes the nature of interhemispheric relationships. The findings suggest that these changes may be one of the causes of extrapyramidal disorders associated with long-term use of the neuroleptic.

Animals↗
PubMed1990

Progressive dystonia following resuscitation from cardiac arrest.

We report a case of a 55-year-old man in whom progressive extrapyramidal disease developed nearly 1 year after resuscitation from cardiopulmonary arrest. Parkinsonian features evolved within 3 months, and progressive generalized dystonia developed after 11 months. CT and MRI revealed bilateral basal ganglia infarction. Autopsy after 4 years of illness showed bilateral basal ganglia necrosis with preserved corticospinal tracts. These findings support earlier suggestions that postinfarction dystonia is mediated by a pyramidal system lacking normal striatal control.

Dystonia↗
PubMed1992

Neuropharmacology of emesis in relation to clinical response.

5-HT3 receptor antagonists such as ondansetron, granisetron, ICS205-930 and zacopride are highly effective in the ferret, cat or dog to prevent emesis caused by cisplatin and other chemotherapeutic agents, and radiation treatment. The anti-emetic effects may be mediated centrally in the area postrema and associated structures of the emetic reflex such as the nucleus tractus solitarius, which have a very high density of 5-HT3 receptors. Additional sites of action may be found on the 5-HT3 receptors located on the vagus nerve or enteric neuronal elements in the gastro-intestinal tract. The precise site(s) and mechanism(s) of action of different cytotoxic treatments to induce emesis remains to be determined, but appears to involve a common action on a 5-HT3 system. The 5-HT3 receptor antagonists do not impair normal behaviour and, in particular, fail to affect the extrapyramidal motor system and do not cause sedation. Of potential benefit, the 5-HT3 receptor antagonists have an anxiolytic profile of action in rodent and primate models. The 5-HT3 receptor antagonists are revealed as an important group of drugs to prevent emesis induced by a wide range of cytotoxic treatments.

Animals↗
PubMed2000

Clinicopathological study of atypical motor neuron disease with vertical gaze palsy and ballism.

The case of a 38-year-old patient with rapidly progressing motor neuron disease, complicated by major dysfunction of the extrapyramidal system and of vertical gaze is described. Neuropathological examination revealed a degenerative process that severely affected the lower motor neurons, as well as the neurons of the pars compacta of the substantia nigra, the nucleus of Darkschewitsch, the nucleus interstitialis of Cajal, the colliculi superiores, and the pallidum. The long tracts were unaffected at all levels of the brain stem and spinal cord. There was no convincing evidence for the presence of a multiple system atrophy or progressive supranuclear palsy; the results rather revealed a pattern of vulnerability characteristic of a variant of motor neuron disease.

Adult↗
PubMedDate not supplied

Type III Machado-Joseph disease in a Japanese family: a clinicopathological study with special reference to the peripheral nervous system.

The clinical and pathological findings in a 58-year-old Japanese man suffering from type III Machado-Joseph disease are reported. The patient became affected at the age of 50 years and presented cerebellar ataxia, progressive external ophthalmoplegia and muscular atrophy, although extrapyramidal signs were never detected throughout the whole course of his disease. His mother, sister and son presented progressive ataxia in the third or fourth decade. The mode of inheritance is considered to be autosomal dominant. Pathological examination revealed severe involvement of the dentato-rubral, ponto-cerebellar and subthalamopallidal systems, spinocerebellar tracts and Clarke's column, cranial motor nuclei including the oculomotor systems and anterior horn cells. The involvement of the substantia nigra was relatively mild, and the nerve cells in the inferior olivary nucleus were well preserved. The distal portion of peripheral nerves was severely damaged. Although the striking feature of Machado-Joseph disease is a considerable variability in the individual clinical expression, there have not been many autopsied cases of this disease and efforts to clarify the clinico-pathological correlation in each phenotype have scarcely been made. Relatively mild changes in the substantia nigra and severe involvement of the peripheral nervous system, as in our case, may be the pathological hallmarks of the type III disorder.

Adult↗
PubMed2004

Review article: clinical implications of enteric and central D2 receptor blockade by antidopaminergic gastrointestinal prokinetics.

Antidopaminergic gastrointestinal prokinetics (bromopride, clebopride, domperidone, levosulpiride and metoclopramide) have been exploited clinically for the management of motor disorders of the upper gastrointestinal tract, including functional dyspepsia, gastric stasis of various origins and emesis. The prokinetic effect of these drugs is mediated through the blockade of enteric (neuronal and muscular) inhibitory D2 receptors. The pharmacological profiles of the marketed compounds differ in terms of their molecular structure, affinity at D2 receptors, ability to interact with other receptor systems [5-hydroxytryptamine-3 (5-HT3) and 5-HT4 receptors for metoclopramide; 5-HT4 receptors for levosulpiride) and ability to permeate the blood-brain barrier (compared with the other compounds, domperidone does not easily cross the barrier). It has been suggested that the serotonergic (5-HT4) component of some antidopaminergic prokinetics may enhance their therapeutic efficacy in gastrointestinal disorders, such as functional dyspepsia and diabetic gastroparesis. The antagonism of central D2 receptors may lead to both therapeutic (e.g. anti-emetic effect due to D2 receptor blockade in the area postrema) and adverse (including hyperprolactinaemia and extrapyramidal dystonic reactions) effects. As the pituitary (as well as the area postrema) is outside the blood-brain barrier, hyperprolactinaemia is a side-effect occurring with all antidopaminergic prokinetics, although to different extents. Extrapyramidal reactions are most commonly observed with compounds crossing the blood-brain barrier, although with some differences amongst the various agents. Prokinetics with a high dissociation constant compared with that of dopamine at the D2 receptor (i.e. compounds that bind loosely to D2 receptors in the nigrostriatal pathway) elicit fewer extrapyramidal signs and symptoms. A knowledge of central and peripheral D2 receptor pharmacology can help the clinician to choose between the antidopaminergic prokinetics to obtain a more favourable risk/benefit ratio.

Antiemetics↗
PubMed1984

[Motor-coordination disorders in patients with infantile cerebral palsy].

A clinico-electrophysiological study of motor-coordinatory impairments was carried out in 117 patients with infantile cerebral paralysis. The results obtained suggest a possibility of a slow rate of myelinization, inadequate development of the coordinatory systems due to early damage to the brain associated with the systemic localization of the defect, and the obligatory involvement of extrapyramidal impairments in the realization of pathological dyskinesias. The clinical and electrophysiological examination made it possible to sum up all clinical manifestations of the pathology under a heading "discoordinatory extrapyramidal dyskinesias".

Adolescent↗
PubMed1990

[MRI pathology of the globus pallidus in a patient with oculogyric crisis and tremor].

A 24-year-old woman developed occasional attacks of oculogyric crisis at the age of 18. She also suffered from postural tremor, dystonic gait, pyramidal tract signs, and peripheral nerve damages. No history of encephalitis was elicited. Nerve conduction velocity revealed decreased velocity and amplitude. Needle electromyography showed a neurogenic pattern. Sural nerve biopsy showed marked Wallerian degenerations. Muscle biopsy revealed small grouped atrophies. It was unlikely that she suffered from juvenile Parkinsonism, and we failed to obtain an evidence of neuronal intranuclear inclusion disease. Recently, Furumoto et al. reported a similar case who developed oculogyric crisis at the age of 12. So far, some authors have reported about changes of MRI image in the putamen and the substantia nigra in extrapyramidal movement disorders. However, few have paid attention to the changes of the pallidum. The most characteristic finding in the present case was the restoration of signal intensity of the globus pallidus on T2 weighted high-field MRI. It is known that pallidal damages produce dystonic disorders. However, the exact role which the pallidum played in pathogenesis of our patient's signs and symptoms is unknown at now.

Adult↗
PubMed1984

[Regressing median peduncular infarction].

A case of a medial and caudal infarction of the midbrain in a 56 years old woman is reported. The clinical syndrome included a rapidly recovering sleepiness, an ophthalmoplegia related to damage to the caudal part of the oculomotor nuclear complex, a slow extrapyramidal dysarthria and a severe ataxia. The latter was characterized by the prevalent involvement of posture control, resulting from an axial hypotonia and the lack of balance reflexes. The CT scan showed a low density area in the central part of the midbrain. Electrophysiological investigations were carried out to study the impairment of the sensory and auditory tracts in the brainstem. In spite of the gravity of initial signs, recovery was good and the patient led a normal life 8 months later.

Ataxia↗
PubMed1998

Metoclopramide toxicity in an infant.

Metoclopramide (4-amino-5-chloro-N-2-methoxybenzamide) is a central and peripheral acting dopamine antagonist. It also stimulates motility in the upper gastrointestinal tract and increases lower esophageal sphincter pressure. In the pediatric population, it is used extensively as an antiemetic and in the treatment of gastroesophageal reflux disease. The case of a six-month-old infant who was accidentally overdosed with 24 mg (3 mg/kg) of metoclopramide within a nine-hour period is presented. The patient demonstrated toxic extrapyramidal effects. There have been multiple early reports in the European literature of acute extrapyramidal reactions in the pediatric population, but no reports of toxicity exist in the current emergency medicine literature.

Antiemetics↗
PubMed1987

Neuropathologic and clinical features of Parkinson's disease in Alzheimer's disease patients.

While dementia in Parkinson's disease (PD) is well described, PD features in Alzheimer's disease (AD) are being increasingly recognized. In 20 neuropathologically confirmed AD brains, 11 cases (55%) showed PD changes (Lewy body formation, neuronal loss, and gliosis of pigmented nuclei), with no significant difference in age or symptom duration between those cases with and without PD pathology. A history of rigidity in the absence of neuroleptic medication was noted in 80% of those with PD pathology but only 14% of those without PD pathology. Tremor was not observed in either group. This suggests that extrapyramidal signs, especially rigidity, noted in many AD patients are related to coexistent PD pathology.

Aged↗
PubMed2004

Transcranial sonography in spinocerebellar ataxia type 3.

BACKGROUND: Transcranial sonography (TCS) identifies hyperechogenic basal ganglia in extrapyramidal disorders such as Parkinson's disease or dystonia and reveals brain atrophy reflecting the stage of degeneration in Huntington's disease. Aim of the present study was to evaluate the diagnostic potential of TCS in spinocerebellar ataxia type 3 (SCA3), a neurodegenerative disease affecting the cerebellum, multiple pontine nuclei, substantia nigra, pallidum, putamen, caudate nucleus and long spinal tracts. METHODS: 15 patients with a molecular diagnosis of SCA3 and 15 age- and sex-matched healthy control individuals were examined with TCS. Echogenicity of the substantia nigra, caudate nucleus, pallidum, putamen, dentate nucleus and cerebellar white matter were determined quantitatively (substantia nigra by measuring the area of incresed echogenicity) or semiquantitatively (0 = none, 1 = mild, 2 = marked) on both sides and compared with the echotexture of defined brain structures. Additionally, the width of the lateral ventricles, the 3rd and 4th ventricle was measured in both groups. RESULTS: SCA3 patients exhibited hyperechogenicities of the cerebellar white matter (57%), substantia nigra (40%), the dentate nucleus (54%), putamen (40%) and pallidum (40%) significantly more frequently (p <0.05) than controls (20%, 13%, 9%, 0%, and 0% in the corresponding areas). In none of the healthy individuals a marked signal increase could be observed, whereas 53% of SCA3 subjects had at least one region with marked echogenicity. Cerebellar atrophy as demonstrated by an enlarged 4th ventricle was observed in all SCA3 patients whereas this structure could not be differentiated from surrounding parenchyma due to its small size in healthy individuals. 3rd and lateral ventricles were significantly larger in SCA patients as compared to controls (p < 0.05). CONCLUSIONS: TCS is a suitable and non-invasive bed-side method to detect basal ganglia hyperechogenic lesions and posterior fossa abnormalities in SCA3 patients. The pattern of echotexture alterations and brain atrophy most likely reflects distribution and morphology of the neurodegenerative process.

Adult↗
PubMed2004

[Bladder sphincter disorders in Parkinson's disease].

Parkinson's disease related to degeneration of the extrapyramidal structures is characterized in its typical form by the classic triad of tremors, rigidity and akinesia, constituting Parkinson's syndrome. These are combined with neurovegetative disorders, responsible for sexual and bladder sphincter dysfunction. The Latter occurs in from 30% to 90% of cases, depending on the stage of progression of the disease. The dopamine deficiency in the nigrostriataL tract leads to a lifting of the inhibition which is probably the cause of the bladder hyperreflexia. Irritative signs are most frequently observed. The flowmetry data are contradictory, depending on the publication whereas the bladder overactivity, objectified by cystomanometry, is described in most of the studies although certain authors report, on the contrary, bladder hypoactivity. Conflicting data have also been published on bladder sphincter dyssynergia although in most studies, micturition was described as synergic in Parkinson's disease patients. L-dopa, the main drug for Parkinson's disease, has, according to the publication, either no action, or contradictory effects with bladder hypoactivity or hyperactivity. Anticholinergics are effective on overactive bladder, the alphablockers on the urethral hypertonia at the price of a higher risk of arterial hypotension in this diathesis. The indication for prostatic surgery must be carefully considered and preceded by precise clinical, urodynamic and sometimes electromyography evaluation. There is a high risk of post surgical incontinence. Endourethral prostheses provide an attractive alternative in the case of prostatic obstruction.

Animals↗