Molecular imaging in hereditary forms of parkinsonism.

The development of in vivo molecular imaging to evaluate the dopamine (DA) system with positron-emission tomography and single photon emission computed tomography has been of key importance on monitoring in vivo nigrostriatal neuronal loss in Parkinson's disease (PD), mostly through assessments of pre- and post-synaptic DA receptors. The discoveries of genes related to hereditary forms of parkinsonism (PARK1, PARK2, PARK6, PARK7 and PARK8) have increased our understanding either of distinct subtypes of clinical expression in PD or its etiology. This article revises current data on molecular neuroimaging of genetic forms of parkinsonism comparing and contrasting its main features with the classical sporadic forms. Awareness of the spectrum variance in the genotype and its respective PD phenotype are useful to distinguish different pathophysiological mechanisms of PD.

Changes in postural control in patients with Parkinson's disease: a posturographic study.

OBJECTIVES: Postural instability is one of the most disabling features in Parkinson's disease (PD), and often leads to falls that reduce mobility and functional capacity. The objectives of this study were to analyse the limit of stability (LOS) and influence of the manipulation of visual, somatosensorial and visual-vestibular information on postural control in patients with PD and healthy subjects. DESIGN: Cross-sectional. SETTING: Movement Disorders Unit, university setting. PARTICIPANTS: Eighty-two subjects aged between 37 and 83 years: 41 with Parkinson's disease in the 'on' state and 41 healthy subjects with no neurological disorders. Both groups were matched in terms of sex and age. MAIN OUTCOME MEASURES: Unified Parkinson's Disease Rating Scale (UPDRS)-motor score, modified Hoehn and Yahr staging, Dynamic Gait Index (DGI) and posturography with integrated virtual reality. The parameters analysed by posturography were LOS area, area of body centre of pressure excursion and balance functional reserve in the standing position in 10 conditions (open and closed eyes, unstable surface with eyes closed, saccadic and optokinetic stimuli, and visual-vestibular interaction). RESULTS: The mean UPDRS motor score and DGI score were 27 [standard deviation (SD) 14] and 21 (SD 3), respectively. Thirteen participants scored between 0 and 19 points, indicating major risk of falls. Posturographic assessment showed that patients with PD had significantly lower LOS area and balance functional reserve values, and greater body sway area in all posturographic conditions compared with healthy subjects. CONCLUSIONS: Patients with PD have reduced LOS area and greater postural sway compared with healthy subjects. The deterioration in postural control was significantly associated with major risk of falls.

Chronic exposure to the fungicide maneb may produce symptoms and signs of CNS manganese intoxication.

Manganese (Mn) poisoning, a well-known hazard in miners and industrial workers, shares many features with Parkinson's disease. Two young agricultural workers with a parkinsonian syndrome, who mentioned exposure to the fungicide maneb (manganese ethylene-bis-dithiocarbamate), led us to investigate a new possible source of Mn intoxication. Fifty male rural workers with occupational exposure to maneb were compared with 19 rural workers without fungicide exposure. We noted significantly higher prevalence of plastic rigidity with cogwheel phenomenon, headache, fatigue, nervousness, memory complaints, and sleepiness in the exposed group. In addition, we saw other neurologic signs, such as postural tremor, cerebellar signs, and bradykinesia, although without statistical significance. The data suggest that occupational exposure to pesticides containing Mn is a possible source of Mn intoxication of the CNS.

Symptomatic dystonia: clinical profile of 46 Brazilian patients.

Dystonia is a syndrome characterized by sustained muscle contraction, provoking twisting and repetitive movements or abnormal postures. It may be classified according to etiology, as idiopathic or symptomatic. We studied 122 Brazilian patients with a dystonic syndrome. Of these, 46 (37.7%) had symptomatic dystonia. The most frequent cause was tardive dystonia (34.8%) followed by perinatal cerebral injury (30.4%). Other causes were stroke (13.0%), encephalitis (6.5%) and Wilson's disease (4.3%). Cranial trauma, mitochondrial cytopathy and psychogenic, were the least frequent causes with one patient in each category. The etiology in two patients could not be established. Perinatal cerebral injury and postencephalitic dystonia were seen in the younger age group, while post-stroke and tardive dystonia were seen in the older age group.

Brain SPECT imaging in Sydenham's chorea.

The objective of the present study was to determine whether brain single-photon emission computed tomography (SPECT) imaging is capable of detecting perfusional abnormalities. Ten Sydenham's chorea (SC) patients, eight females and two males, 8 to 25 years of age (mean 13.4), with a clinical diagnosis of SC were submitted to brain SPECT imaging. We used HMPAO labeled with technetium-99m at a dose of 740 MBq. Six examinations revealed hyperperfusion of the basal ganglia, while the remaining four were normal. The six patients with abnormal results were females and their data were not correlated with severity of symptoms. Patients with abnormal brain SPECT had a more recent onset of symptoms (mean of 49 days) compared to those with normal SPECT (mean of 85 days) but this difference did not reach statistical significance. Brain SPECT can be a helpful method to determine abnormalities of the basal ganglia in SC patients but further studies on a larger number of patients are needed in order to detect the phase of the disease during which the examination is more sensitive.

Idiopathic dystonia. Clinical profile of 76 Brazilian patients.

Dystonia may be classified by age of onset (childhood, adolescence, adult onset), body distribution of the abnormal movements (focal, segmental, unilateral, multifocal and generalized) and etiology (idiopathic and symptomatic). We studied 76 patients with idiopathic dystonia among 122 cases of dystonic syndrome (62.3% of the total). There were 48 female and 28 male patients. Adult-onset focal dystonia was the most frequent feature (37 patients). The onset of generalized dystonia was more frequently seen under the age of 20, whereas focal and segmental dystonia usually started over this age. Postural tremor of the hands was observed in 19.7% of the patients. Spasmodic torticollis was the most prevalent form of dystonia overall. Except for writer's cramp, which occurred more frequently in males, and generalized dystonia, which was equally divided between sexes, all other forms were more frequent in females. Our data suggest that differences in racial origin, social and economical status and environmental factors do not account for a different manifestation in dystonia pattern.

[Chorea: clinical analysis of 119 cases]. / Coréia. Análise clínica de 119 casos.

Chorea is a clinical syndrome characterized by abnormal involuntary arrhythmic movements, randomly distributed in time, affecting mainly the distal parts of the limbs. There are many diseases associated with chorea but the distribution of the etiologies vary too much in different parts of the world. We intended to study the etiologies of chorea in a Movement Disorders Unit of a university hospital-based outpatient clinic in Brazil. We studied the records of 119 patients with chorea based in the diagnostic criteria of the World Federation of Neurology. Sydenham's chorea (SC) was the most frequent cause of chorea (51.3%) of our sample. Other common causes were Huntington's chorea (18.5%) and chorea post-stroke (9.2%). SC is not commonly seen in developed countries nowadays but is not rare in Brazil. SC patients generally have the clinical manifestation of it in the first 20 years of age and girls are more affected than boys and this feature was observed in our sample. Based on our own experience and in the review of the literature we propose an etiological classification of chorea.

[Essential tremor: clinical characterization in a sample of 176 patients]. / Tremor essencial: caracterização clínica de uma amostra de 176 pacientes.

We reviewed the clinical records of 176 patients with essential tremor (ET) according to sex, age of onset, family history, tremor characteristics and body distribution. The patients were divided into two groups: familial (F) and non familial (NF). A positive family history for tremor was observed in 47.2% of the patients. Action and postural tremor were the most frequent characteristic (49.4%), postural alone in 26.7% and action alone in 9.1%. Rest tremor was recorded in 10.2%, always associated with other characteristics. There were no clinical differences between the F and NF groups. Hands were involved in 94.9% and the head in 26.5%. Isolated tremor of the hands was the most frequent form of presentation with some greater frequency in males. Sixty per cent of the patients who presented head tremor either isolated or not, were females. The presence or absence of family history did not show difference in this proportion. The age of onset ranged between 4 and 85 years. In the F group a lower mean of onset (36.5 years) was seen in males with statistical significance. In male patients with combined action and postural tremor a lower age of onset was found. The fact of a patient having either parent affected by ET produced no difference in the age of onset. Familial or non familial ET bearing some differences, may not be considered as distinct entities.

[Levodopa-induced dyskinesia in 176 patients with Parkinson's disease]. / Discinesias induzidas por levodopa em 176 pacientes com doença de Parkinson.

Dyskinesias are frequently observed in parkinsonian patients during levodopa treatment. The occurrence of these movement disorders usually makes the therapeutic management of the patients very difficult. The clinical characteristics of 176 patients with dyskinesias were retrospectively studied. Dyskinesias occurred, on average, after 6.2 years of duration of Parkinson's disease and after 4.2 years on treatment with levodopa. Patients were more likely to have dyskinesias during more advanced stages (measured by Hoehn and Yahr scale). Peak of dose and square wave were the types of dyskinesia more frequently described and were associated with choreic movements in most cases. Dystonia occurred in 40% of the cases and was predominant in end of dose and diphasic dyskinesias. Thirty-five percent of dystonia cases presented as "early morning dystonia". Chorea was the most frequent involuntary movement and mostly generalized. Dystonia was most commonly described in lower limbs. Orofacial dyskinesia, when occurred alone, was more frequently seen in old rather than young patients. When dyskinesia was unilateral it was more likely to occur in the side where Parkinson's disease was more severe.

Rural or urban living and Parkinson's disease.

Although the precise etiology of Parkinson's disease (PD) is as yet unknown, it appears that certain environmental factors are involved. Prior living in a rural area has been implicated as a possible risk factor for PD, particularly in the early onset type. We evaluated the role of previous living conditions in the clinical correlates and outcome characteristics of 118 PD patients. All of them were seen from January 1987 to October 1992. The Rural Group (RG) comprised 71 patients (60.2%) who had lived in the rural area for at least 10 years (mainly in early phase of life) and the Urban Group (UG) consisted of 47 patients (39.8%) who had lived their entire life in an urban environment. The average age at the beginning of the symptoms was 58.8 in the RG and 54.1 in the UG. The mixed form of the disease (tremor, rigidity and akinesia) was the most frequent in both groups. A minimum 6-month follow-up period was undertaken with 63 patients (average 20 months) and no difference in response to treatment or in progression of the illness was detected between the two groups. Our data show that the previous living environment does not appear to be a determining factor in either the clinical or outcome characteristics of PD.

[Apomorphine: an alternative in the control of motor fluctuations in Parkinson's disease]. / Apomorfina: uma alternativa no controle das flutuações motoras na doença de Parkinson.

Levodopa-induced motor fluctuations (MF) is a disabling complication of Parkinson's disease (PD) and is usually refractory to conventional treatment. Apomorphine, a dopamine agonist with affinity for both D1 and D2 receptors, has been emerged as an useful alternative in the management of MF of PD. The frequency of nausea and vomiting prevented its use in the past, but the simultaneous administration of domperidone has proved to be able to control these side effects. Although apomorphine has been successfully used to control levodopa-induced MF in other countries, it has not been considered in the management of PD in Brazil. We report here our initial experience with subcutaneous injections of apomorphine combined to oral domperidone. We administered apomorphine in doses ranging from 1.5 to 3 mg in four PD patients with MF of our outpatient clinic. All the doses administered switched the "off" state to a motor response qualitatively similar to what is seen in the "on" phase induced by levodopa, including the occurrence of dyskinesia. The latency to turn "on" after apomorphine ranged from 7 to 30 minutes and the duration of the response ranged from 60 to 85 minutes. We observed yawning in all four patients, labial paresthesia in one patient and an inspecific unpleasant sensation in another patient. These side effects were not significant in our four patients. Our data show that the use of apomorphine adds a reliable and effective strategy in the management of MF of PD patients.

Complex partial seizures and aphasia as initial manifestations of non-ketotic hyperglycemia. Case report.

We describe a case of non-ketotic hyperglycemia (NKH), heralded by complex partial seizures and aphasia of epileptic origin, besides versive and partial motor seizures. This clinical picture was accompanied by left fronto-temporal spikes in the EEG. The seizures were controlled by carbamazepine only after the control of the diabetes. A month later, carbamazepine was discontinued. The patient remained without seizures, with normal language, using only glybenclamide. Complex partial seizures, opposed to simple partial seizures, are rarely described in association to NKH. Epileptic activity localized over language regions can manifest as aphasia.

[Postural tremor and dystonia. Clinical aspects and physiopathological considerations]. / Tremor postural e distonia. Aspectos clínicos e considerações fisiopatológicas.

The coexistence of tremor and dystonia is usually seen but there is not a satisfactory explanation for it. Some consider that essential tremor (ET) and idiopathic dystonia (ID) may be genetically linked. To clarify this relationship we evaluated the frequency of postural hand tremor in ID and symptomatic dystonia (SD) patients. We studied the records of patients with dystonia seen in our Movement Disorders Unit. ID was considered when there was no other neurological abnormality in the examination aside from dystonia, normal laboratorial tests and neuroimaging related to dystonia, and a negative past history for any known cause for it, except for genetic predisposition. We analyzed the clinical characteristics of dystonia and the occurrence of postural tremor. We collected 185 patients, being 120 with ID and 65 with SD. Tremor was seen in 27 (22.5%) of ID and 14 (21.5%) of SD. Tremor was present in either focal, segmental or generalized dystonia in both ID and SD. Family history for ET was absent in all patients. The similar frequency of tremor in ID and SD patients suggests that the pathophysiologic derangement resulting in dystonia can favor the development of tremor.

A study on the action of two calcium channel blockers (verapamil and flunarizine) upon an experimental model of tardive dyskinesia in rats.

Tardive dyskinesia (TD), a serious complications of neuroleptic chronic use, has no effective therapy yet. We performed an experiment to study the action on TD, of the calcium channel blockers (CCB) drugs, verapamil and flunarizine. We obtained the TD model in rats, administering haloperidol for a 21-day period. After this, the stereotyped movement induced by apomorphine was rated. The CCB drugs were administered in acute (in the 28th day) and chronic (for 8 days, after the 25th day) experiments. Acutely, verapamil increased the stereotyped behaviour, and promoted a reduction of it in the chronic experiment. The results suggest that CCB drugs should be tested in clinical trials of TD.

[Botulinum toxin A: experience in the treatment of 115 patients]. / Experiência com aplicação de toxina botulínica a em 115 pacientes.

Botulinum toxin A is the more efficient therapy of focal dystonias and hemifacial spasm. Our experience with botulinum toxin A injections in 115 patients is reported. Marked or total improvement was achieved in all 45 patients with hemifacial spasm, in 70% of 20 patients with essential blepharospasm and in 71.4% of 14 patients with Meige's syndrome. In 65.2% of 23 patients with cervical dystonia marked but no total improvement was obtained. The worse results were seen in the 6 patients with hand dystonia (writers cramp), in whom marked improvement was obtained in just two. Mild and transient complications occurred in up to 24.4%, eyelid ptosis and eyelid weakness being the most frequent. One patient with Meige's syndrome had an aspiration pneumonia following dysphagia. Our results are in agreement with others, showing that botulinun toxin A is a useful and safe treatment for these conditions.

The action of prolyl-leucyl-glycinamide (PLG) on the nigrostriatal pathway of the rat.

In order to study the nigrostriatal pathway, we obtained the rotatory behavior model in male Wistar rats by electrolytic lesion of the left lateral hypothalamic region. Animals thus lesioned displayed rotations toward the same side of lesion when apomorphine was administered, a result in disagreement with what has been obtained in the model with 6-hydroxydopamine lesion. The administration of PLG alone was not followed by rotatory behavior but when the compound was administered in low doses (0.25 to 1mg/kg) simultaneously with apomorphine to animals previously submitted to REM sleep deprivation, a significant increase in the number of rotations was observed in comparison with controls and groups receiving higher doses of PLG. These results indicate that PLG may act as a modulator on dopamine receptors in the striatum.

Hemorrhagic cerebral metastasis as a first manifestation of a hepatocellular carcinoma. Case report.

We report herein a rare instance in which a patient presented with a hemorrhagic cerebral metastasis as the initial manifestation of a hepatocellular carcinoma (HCC). A few cases of cerebral metastasis from HCC have been reported in the literature, mainly from eastern countries. This is the first report from South America of a cerebral metastasis from hepatocellular carcinoma.

[Stereotaxic thalamotomy and pallidotomy with computerized planning in Parkinson's disease: short-term evaluation of motor function in 50 patients]. / Talamotomia e palidotomia estereotáxica com planejamento computadorizado no tratamento da doença de Parkinson. Avaliação do desempenho motor a curto prazo de 50 pacientes.

We evaluated the motor function of 50 patients with Parkinson's disease, who underwent stereotaxic surgery with computerized planning, without ventriculography (ventrolateral thalamotomy- VLT- and/or posteroventral pallidotomy- PVP) before and one month after surgery. 27 unilateral TVL, 10 unilateral PVP, 6 bilateral PVP, and 7 TVL with PVP were performed. The motor evaluation was performed with the Unified Parkinson's Disease Rating Scale, motor score, during on and off periods. We observed a global motor improvement in all groups. The improvement of dyskinesias was obtained in the contralateral side of the body, in the PVP groups. From the 50 patients, 16 (32%) presented post-operative complications, 9 of these (56.25%) improved completely, 6 (37.25%) improved partially, and 1 (6.25%) did not improve during the first month. These results were considered satisfactory, and a long term analysis will show whether these benefits are long lasting or not.

[Cerebral venous thrombosis and homocystinuria: case report]. / Trombose venosa cerebral e homocistinúria: relato de caso.

Homocystinuria presenting as cerebral venous thrombosis is not usual. We report on a 13-year-old boy who was admitted to the hospital due to severe headache, nausea, vomiting and fever (38 degrees C). The patient was Marfan like and presented left hemiparesis and meningeal irritation sings. He was mentally retarded, had severe myopia, and had right lens dislocation one month before. Cranial CT scan was suggestive of cerebral venous infarct. MRI and magnetic resonance angiography showed venous infarcts more prominent in the right thalamic projection with hemorrhagic transformation and multiple foci of cortical (occipital and parietal bilaterally) deep parietal and left capsular bleeding, secondary of thrombosis of the transverse and sigmoid venous sinuses. High levels of homocysteine were detected in the blood and urine. Homocystinuria is an autosomal recessive inborn error of methionine metabolism caused by cystathionine-beta-synthase defect in most cases. We discuss the clinical and radiological findings in this patient, analyzing the pathophysiology of the thrombotic events related to homocystinuria.

The diagnosis of delirium in 80 emergency unit patients.

We evaluated the initial and final diagnosis of 80 patients with delirium arriving at the emergence unit of a university hospital in a large Brazilian city over a period of 30 months up to December 1991. The diagnosis was based on the DSM-IIIR criteria. Patients with a known history of head trauma or epileptic seizure and patients younger than 13 years were excluded. Only patients with a disease of up to 7 days were included. The patients were subdivided into four etiologic groups: vascular; associated with the use of alcohol; infectious-parasitic; miscellaneous. The results showed a rate of correct diagnosis ranging from 65 to 80% with the use of kappa test (standard good to excellent). Sensitivity, specificity, positive predictive and negative predictive values had results showing different conditions for initial diagnosis in each group. This study can help the initial diagnosis of delirium and the choice for diagnostic testing.