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[Impairment of social cognition in Parkinson's disease].

The characteristic four symptoms of motor deficits, bradykinesia, rigidity, resting tremor and impairment of postural reflex with Parkinson's disease (PD) are accompanied by specific cognitive deficits. Deficits of executive functions, skill learning, and visuospatial cognition are well known. The results of our recent studies show the deficit of social cognition which include facial expression recognition, sensation of gaze direction, "theory of mind" in comprehension, and decision making. These symptoms can be explained by the damage of the amygdala and/or its connection, which are known to play a crucial role in social cognition, it is attributed to the involvement of amygdala and it's connection to the frontal lobe in PD. The impairment of social cognition is an important mental change associated with PD.

Cognition Disorders↗

Effect of isatin (2,3-dioxoindoline) on audiogenic seizures in rats and its relationship to electrographic and behavioural phenomena.

In doses of 160 and 80 mg/kg, isatin (2,3-dioxoindoline) significantly reduced the total incidence of audiogenic epileptic seizures in rats highly sensitive to an acoustic epileptogenic stimulus. The number of severest forms of seizure (running, clonic convulsions) was higher than in the control tests, however. The acoustic epileptogenic stimuls was applied one hour after the i.p. injection of isatin. At that time some postural reflexes were still inhibited after 160 mg isatin/kg, while after smaller doses they were already normal again. One hour after administering isatin there were marked changes in the electroencephalogram, the chief ones being an increase in rhythmic episodic activity against a desynchronization background and a decrease in slow wave sleep activity.

Acoustic Stimulation↗

[Pure akinesia presenting with antecollis].

We reported a 77-year-old woman having pure akinesia who presented with antecollis induced by L-threo-3, 4-dihydroxyphenylserine (L-DOPS). At the age of 70, she noticed increasing difficulty in standing up from a seat and moving. Afterward, she developed gait disturbance with difficulty in initiating walking, frozen gait, and postural instability. At 73 years of age, she came to our hospital, because she gradually fell down easily. Neurological examination disclosed mild akinesia with freezing symptom and kinésie paradoxale. No evidence of dementia, supranuclear gaze palsy, pseudobulbar palsy, rigidity, or tremor were present. As she developed akinesia, of which L-dopa therapy achieved little improvement, we clinically diagnosed as having pure akinesia. At age 74, L-DOPS was administered at a dose of 300mg per day and gradually increased up to 900mg per day, because her postural reflex was markedly disturbed and gait showed severe unsteadiness. Amelioration of frozen gait and unsteadiness were recognized, but efficacy of L-DOPS was temporal. It is well known that reported cases of pure akinesia were pathologically diagnosed as having progressive supranuclear palsy (PSP) or pallido-nigro-luysian atrophy. Therefore, the present case was suspected as having pathological changes which involved degeneration of the substantia nigra and globus pallidus. After three years of treatment with L-DOPS, at age 77, she was admitted to our hospital for abrupt onset of her dropped head. Hematological examinations were normal, cervical MRI showed no evidence of paracervical muscular atrophy, and electromyography did not demonstrate any abnormal change. In addition, her posterior cervical muscles showed abnormally high tension, so the dropped head was considered due to antecollis. After admission, antecollis disappeared rapidly following discontinuation of L-DOPS. However the mechanism of drug induced dystonia is imperfectly understood on the basis of the clinical course, L-DOPS was considered as possible cause of her antecollis. L-DOPS, artificial precursor of noradrenarine (NA), is thought to increase not only NA level in the CNS, but also inhibit release of acetylcholine. It is suggested that the antecollis of present case results from impairment of a normal dopaminergic-noradorenergic balance caused by increased NA and striatal dopamine deficiency. This is the first case of antecollis induced by L-DOPS in a pure akinesia patient, providing important information on mechanism of drug induced dystonia and indicating caution in the clinical use of L-DOPS.

Aged↗

A differential diagnosis of Parkinsonism.

Parkinsonism is a common, age-related syndrome, characterized by resting tremor, bradykinesias, rigidity, and postural reflex impairment. Though Parkinsonism is not very difficult to recognize, all Parkinsonism is not created equal and it is important to distinguish among the most common identifiable syndromes. This review discusses the key clinical features of these various syndromes, including Parkinson's disease, progressive supranuclear palsy, multiple system atrophy, corticobasal ganglionic degeneration, Lewy body disease, vascular Parkinsonism, and Parkinsonism with no clear etiology. Symptomatology and diagnostic testing for each syndrome are discussed and 4 typical cases are analyzed to offer clinicians guidance in making a differential diagnosis for Parkinsonism.

Brain↗

Falls in Parkinson's disease. Causes and impact on patients' quality of life.

The aim of this study was to investigate the prevalence of the different causes of falling in Parkinson's disease (PD) and to evaluate the influence of falls on patients' quality of life (QoL). We recruited 60 PD patients (31 with falls, 29 without falls). We found that falls were caused by: unstable posture (29.0%), freezing or festination (25.8%), sudden loss of postural reflexes (toppling falls) (25.8%), co-existing neurological disorders (6.5%), cardiological disorders (6.5%), and symptomatic orthostatic hypotension (3.2%). Duration of the disease was longer, its stage more advanced, daily levodopa dosage higher, and the proportion of patients with abnormalities in the EEG apparently greater in the group with falls. The presence of falls was found to be a factor contributing to a multidirectional negative impact on patients' QoL. QoL also depended on impairment of cognitive function, daily dosage of levodopa, disease duration, disease progression, and sex. The results of this study underline the need to diagnose the causes of falls in order to institute appropriate treatment and to improve patients' QoL.

Accidental Falls↗

Sympathetic reflex control of blood flow in human peripheral tissues.

Sympathetic vasoconstrictor reflexes are essential for the maintenance of arterial blood pressure in upright position. It has been generally believed that supraspinal sympathetic vasoconstrictor reflexes elicited by changes in baroreceptor activity play an important role. Recent studies on human skeletal muscle, cutaneous and subcutaneous tissues of the limbs indicate that the situation is more complex. Measurements have been carried out during acute as well as chronic sympathetic denervation. Spinal sympathetic reflex mechanisms have been evaluated in tetraplegic patients, where supraspinal sympathetic vasoconstrictor reflexes are blocked. Blood flow has been measure by the local 133Xe-technique. The results indicate the presence of spinal as well as supraspinal sympathetic vasoconstrictor reflexes to human peripheral tissues. Especially is emphasized the presence of a local sympathetic veno-arteriolar axon reflex which is elicited by increase in venous transmural pressure of more than about 25 mm Hg. Finally, centrally elicited vasoconstrictor activity is modified by simultaneously activating the local veno-arteriolar axon reflex or vice versa by means of an intraneuronal impulse inhibition due to collision of normodromically and antidromically conducted impulses in efferent sympathetic vasoconstrictor fibers. The evidence obtained suggests that sympathetic vasoconstrictor reflexes to postural changes are complex and highly differentiated.

Blood Pressure↗

The significance of foliation and fissuration of cerebellar cortex. The cerebellar folium as a fundamental unit of sensorimotor integration.

I propose the general hypothesis that each individual folium in the cerebellum is an integrative module that is involved in unique sets of sensorimotor transactions. Although the basic types of operations carried out by cerebellar cortex may be similar in all folia, the mosaic of afferent sources, intrinsic organization and efferent destinations appear to be unique for each folium. I believe that this conception is supported by: 1) comparative data which illustrate species-typical folial patterns, 2) neuroanatomical data which reveal not only different structural features of folial crowns and fundi, but differential afferent and efferent connectivity of different folia as well, 3) physiological data, which demonstrate unique patterns of afferent activity in different folia, and especially by 4) ontogenetic data which establish that each folial crown expands and differentiates into an architecturally distinct cortical entity. Taken together, all these lines of evidence suggest that the numbers and patterns of folia exhibited by the cerebellar cortex of different mammals are morphological indicators of differential organization of sensorimotor control functions in each animal. Even intraspecific individual variations in folial number, size and pattern may signify structural-functional determinants of some individual differences in sensorimotor transactions. Since so little research has addressed the many testable ideas embodied in these general hypotheses, it seems to me that neuroscientists have a long way to go to clarify how the many different folia and lobules of cerebellar cortex actually function in the common, everyday, orderly, dynamic and ongoing reflex, postural, learned and deliberate behavioral sequences that characterize the normal behavioral repertoires of different animals. The enormous advances in understanding brought forth by the extensive research and writings of Professor Brodal and his colleagues have expanded our horizons to avail us of an enormous range of new vistas into cerebellar functional morphology. It is now the task of neurobiologists to explore these diverse new domains in ever greater depth and detail.

Animals↗

[Oculogyric crisis as an initial symptom of juvenile parkinsonism-like disease].

A 12-year-old boy developed occasional attacks of oculogyric crisis after physical exercises or when tired. Following the initial symptom, progressive Parkinsonian features such as bradykinesia, muscular rigidity, hand tremors in posture, mild dysarthria and disorder of postural reflexes developed. There was no marked diurnal fluctuation o symptoms. Serum ceruloplasmin, copper levels, cranial X-ray CT scan and MRI were normal. Measurement of the plasma levels of L-dopa after single oral administration (300 mg) were normal. The treatment with L-dopa improved the Parkinsonian features excluding the attacks of oculogyric crisis in a few weeks. This case is not identical with juvenile Parkinsonism proposed by Yokochi et al for lack of both crural or truncal dystonia and remarkable response to L-dopa. Oculogyric crisis is known in several patients with severe generalized dystonia, and seldom in patients with Parkinson disease or juvenile Parkinsonism. Oculogyric crisis may be one of focal dystonias confined to extraocular muscles.

Adolescent↗

[Clinical and physiological study of apraxia of gait and frozen gait].

A study of clinical features and an analysis of gait with floor reaction forces and EMG of leg flexors and extensors were made in patients with multiple cerebral infarction or patients with Parkinson's disease having frozen gait. A case with occlusion of the bilateral anterior cerebral arteries resulting in massive infarction of the infero-medial part of the frontal lobes was also studied as he showed a unique disorder characterized by apraxia of gait. Frozen gait is characterized by shuffling steps, broad-based stance, positive foot grasp, kinesia paradoxa and disturbance of postural reflexes. The vector angle which shows foot pressure in forward locomotion was decreased in patients with frozen gait. EMGs of lower leg muscles in frozen gait were grouping of potentials corresponding to the shuffle and reciprocity between flexors and extensors was preserved. The patient with infarction of the bilateral anterior cerebral arteries showed a peculiar disorder of gait which was characterized by an inability to initiate stepping. It is considered as "apraxia of gait" in a classical sense, which differs from frozen gait. Observation of this patient suggests that the infero-medical part of the frontal lobe plays an important role in the initiation of gait. Furthermore, common features of frozen gait in patients with Parkinson's disease and in patients with multiple cerebral infarction involving the frontal lobe suggest that the nigrostriatal structures and the frontal lobe are important in CNS mechanisms subserving smooth locomotion.

Aged↗

Reversal of ketamine/xylazine anesthesia in the rabbit with yohimbine.

Ketamine and xylazine used in combination have been shown to be effective, easily administered, cost efficient agents for surgical anesthesia in the rabbit. The effect of xylazine on the central nervous system has been shown to be mediated through alpha-2 adrenergic receptors. Yohimbine, an alpha-2 adrenergic antagonist has been shown to reverse xylazine induced depression and partially antagonize ketamine in other species. We evaluated the antagonistic effect of yohimbine on ketamine/xylazine anesthesia in the rabbit. Six New Zealand White rabbits were anesthetized with intramuscular ketamine (50 mg/kg) and xylazine (10 mg/kg) to establish baseline parameters including respiratory rate, heart rate, and palpebral, pedal and postural reflex activity. Fourteen days later each rabbit was subjected to the same anesthetic regimen followed 30 minutes later by the intravenous administration of yohimbine (0.2 mg/kg). The duration of anesthesia estimated by the time elapsed between the loss and return of the palpebral reflex was reduced in the yohimbine treated trial (means = 29.7 +/- 1.9 minutes) compared to the control trial (means = 67.0 +/- 13.5 minutes). The palpebral reflex returned within 5 minutes following yohimbine treatment. Our results indicated that yohimbine is an effective antagonist of ketamine/xylazine anesthesia in the rabbit. Yohimbine decreases anesthetic duration after intravenous administration and also may aid in the control of undesirable anesthetic effects and overdosage.

Anesthesia↗

General pharmacology of brotizolam in animals.

Brotizolam (2-bromo-4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f]-1,2,4-triazolo [4,3-a]-1,4-diazepine, We 941, Lendormin) is a thienotriazolo-diazepine with profound sedative and hypnogenic properties. The side effects of the drug on general behavior, motocoordination, feeding pattern, body temperature, uropoietic and gastrointestinal functions, cardiovascular system, and respiration, as well as interactions with some biogenic amines are reported and discussed. The findings correlate with those known for other diazepines. Accordingly, effects on motocoordination were prominent, but were limited to an ataxia, whereas even extremely high doses scarcely eliminated the postural reflexes. Sleeping animals could invariably be woken and were capable of locomotion; thus, no comatose condition developed. The cardiovascular functions were not appreciably altered by brotizolam in anesthetized cats, while in conscious dogs minor fluctuations of blood pressure and heart rate occurred. Respiration was clearly inhibited when brotizolam was given intravenously. The cardiovascular effects of acetylcholine, norepinephrine, epinephrine, isoprenaline, and histamine were only slightly modulated. The orexigenic and hypothermic effects equalled those of other diazepines. The functions of kidney, stomach, and intestines were not affected. The entirety of the observations procured in ten different species suggest that brotizolam is well tolerated when given orally.

Animals↗

[An autopsy case of progressive supranuclear palsy showing "pure akinesia without rigidity and tremor and with no effect by L-dopa therapy (Imai)"].

Eleven cases of "pure akinesia without rigidity and tremor and with no effect by L-dopa therapy" were first reported by Imai in 1980. Three cases were added by Hayashi and Hayashi (1983). However there have been so far no autopsy cases, remaining the nosological position of this syndrome uncertain. The authors have had an opportunity of observing the third case in the report by Hayashi and Hayashi for 8 years and autopsy was done as well. Case report The patient was a female farmer. On account of postural-reflex troubles, the pulsion phenomenon and feet freezing, which had progressed since the age of 54, she easily tumbled over. Eight years after the beginning of those symptoms, vertical oculomotor palsy, pseudobulbar palsy and dementia were added; she was diagnosed as a progressive supranuclear palsy. Before this diagnosis, her illness was being regarded as "pure akinesia without rigidity and tremor and with no effect by L-dopa therapy". Neck dystonia was not observed even in the terminal stage. She died at the age of 65. The total clinical course was about 11 years. Pathological observation The brain weighed 1,170 g before fixation. Marked atrophy of the subthalamic nucleus, globus pallidus and pontine tegmentum was observed. The substantia nigra was shown to be severely depigmented. Microscopically, loss of neurons and gliosis were seen in the subthalamic nucleus, globus pallidus, substantia nigra, hypothalamus, superior colliculus, central grey matter, brain stem reticular formation, cerebellar dentate nucleus, etc. The characteristic finding was the appearance of neurofibrillary tangles in these regions.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Behavioral teratology--results achieved and perspectives of development.

The objective of behavioral teratology is to throw light on the consequences of prenatal effect of the agent on varying aspects of the functional state of the nervous system. In the present paper, the author proposes Carbendazim as a model of Type 1 behavioral teratogen (agent provoking morphological anomalies in the CNS). On this model, the author studied the sensitivity of a group of primary screening tests proposed in the literature, introducing semiquantitative and quantitative criteria for determining the level of response. The study of the postural reflex and behaviour in the open field were found to be the most sensitive. The latter also provides the possibility of demonstrating some qualitative deviations in behaviour, such as the "jumping" gait.

Abnormalities, Drug-Induced↗

[Cerebral palsy--early diagnosis and treatment (author's transl)].

The main aim of the present Conference has been to debate that early diagnosis and treatment of cerebral palsy. The Conference was attended by specialists taking care of the child with cerebral palsy (C.P.): child neurologists, surgeons--orthopedists, psychologists, rehabilitants, pediatricians. In connection with the fact that the Conference was devoted to the early diagnosis and therapy of C.P., problems concerning the lower age groups of children were debated. The Conference discussed the definitions of "cerebral palsy" used in the literature, the clinical forms, the auxiliary diagnostic methods and their significance in the diagnosing of this pathological syndrome. Early clinical symptoms, enabling to establish the diagnosis of cerebral palsy were particularly extensively debated. In the latter problem particular attention was paid to the diagnostic value of kinetic automatisms of the group of tonic posture reflexes and dysfunctions of the kinetic pattern in children. It was underlined in the debate the C.P. was no separate clinical disease, but a pathological syndrome arisen as a result of the negative influence of different factors and yielding very diverse clinical and neurolopathologic symptoms, according to the kind of noxious factors and the period and degree of maturity of the nervous system in which they acted. The participants in the debate also sressed that, as the child develops and is observed for a longer period it is fairly often necessary to check this diagnosis, as C.P. may prove, as the time passes, to be a degenerative syndrome, a pressure syndrome etc. The psychologists participating in the Conference discussed the psychological problems of the child with C.P. and also the early diagnosis of the pathological syndrome debated. The diversity of the symptoms of the C.N.S. in children suffering from C.P. was underscored, as--apart from dysfunctions within the kinetic area, there can be present sight, hearing and speech dysfunctions, those of sensory perceptions and mental development. These children require multispecialist care, as everyone of dysfunctions mentioned may present a complicated diagnostic problem. Plenty of place was devoted to the discussion of problems connected with epilepsy in children with C.P. Also extensively debated were the general principles of the medical procedure in children with C.P. As a result of the discussion it was decided that children with severer forms of C.P. and those from poor social conditions should be subjected to long-lasting sanatorium rehabilitation. Keeping the child in its family environment should, however, be the generally adopted principle of the rehabilitation of a little child. The parents of the child should be trained in the proper rearing of the child under household conditions, a manner to secure all the needs resulting from the then stage of its development. In connection with this problem the project of the programme of sensoric-and-kinetic rehabilitation was debated, as presented by psychologists and rehabilitants (kinesitherapeuts).

Age Factors↗

[Possibilities of control of regulation of the function of arteriovenous anastomoses and of capillary blood flow by means of acupuncture].

Acupuncture was carried out on a patient with rheumatoid arthritis and microangiopathy of the lower limbs. Photoplethysmographic waves appeared at the right inferior limb where before they had been absent; at the left inferior limb normalization of postural reflexes was achieved, suggesting that acupuncture is effective in vasodilatation of capillaries and preterminal arterioles and in the reactivation of the arterio-venous blood flow.

Acupuncture Therapy↗

[Autotopagnosia ameliorated by looking at the image reflected in a mirror].

A 52-year-old right-handed man presented progressive dystonia and apraxia of his right hand of five years' duration. He also suffered from parkinsonian features such as rigidity or impaired postural reflexes. Serial investigation of brain MRI revealed progressive cerebral atrophy, which started in the left parietal lobe, and subsequently extended to both hemispheres. He was clinically diagnosed as corticobasal degeneration. He could not point at any part of his own body in response to verbal or visual commands. On the other hand, he could point at every part of the examiner's body or of the illustrated body image. Deep sensations and linguistic functions were not involved. This cognitive impairment was regarded as autotopagnosia. In contrast with inability to recognize any part of the own body in response to the commands, he could name every part of his body as soon as the examiner touched there. Moreover, his symptoms of autotopagnosia were ameliorated by looking at himself in a mirror; he could point at any part of his own body. Disconnection between primary proprioceptive sensory area and the center of body schema was thought to be the mechanism of autotopagnosia in this patient, because the impairment improved with the aid of visual or tactile informations. We speculated the lesion was the left parietal lobe.

Agnosia↗

[Progress in diagnosis and treatment of juvenile parkinsonism].

The diagnosis and treatment of juvenile parkinsonism (JP) is described. There was a high incidence of familial JP (58.1%), and its inheritance pattern was usually an autosomal recessive type. The patients with JP presented with improvement of parkinsonian symptoms following sleep and dystonic posture of the feet as specific signs. The tremor was a fine postural, and impairment of postural reflex was prominent. In the treatment of JP, it is important to control the wearing-off phenomenon and the dopa-induced choreic dyskinesia usually occurring in the extremities. A small dose of levodopa with decarboxylase inhibitor has to be carefully administered several times a day. The clinical course of JP is very slowly progressive compared with that of Parkinson's disease.

Adolescent↗

[A family of parkinsonism in which the clinical feature of constituents varied with the age of onset].

We report a family of parkinsonism in which the clinical feature of the constituents varied with the age of onset. The propositus was a 49-year-old woman who had developed tremor and akinesia at the age of 26 years. Levodopa markedly relieved her symptoms. The feet showed pes equinovarus with tonic extension of the great toe. The most characteristic feature was marked diural fluctuation of her symptoms; her gait was nearly normal in the morning, while she showed marked tremor and gait disturbance with parkinsonian posture in the evening. Sleep markedly improved her conditions. Her maternal uncle developed parkinsonism at the age of 60 years, and anti-parkinsonian drugs including levodopa were persistently effective. Neurological examination at the age of 75 years revealed parkinsonian features with rigidity, resting tremor, akinesia and loss of postural reflex, together with severe pes equinovarus and tonic extension of the great toe. There was no diural fluctuation in his symptoms. Several types of dystonia-parkinsonism, either familial or sporadic, have been reported in the literature, but none of them showed the same clinical and genetic features as the present family. The present family may be included in a spectrum of dystonia-parkinsonism syndrome of autosomal-dominant inheritance.

Age of Onset↗