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PubMed2005

Estimation of early postmortem intervals by a multiple regression analysis using rectal temperature and non-temperature based postmortem changes.

Five general methods based on rectal temperature and a multiple regression analysis using rectal temperature and non-temperature based postmortem changes were applied to 212 postmortem cases of within 24h postmortem (PM) intervals. Non-temperature based postmortem changes of rigidity, hypostasis and corneal turbidity were numerically categorized and used with rectal temperatures as four statistical variables in the multiple regression analysis. The correlation coefficient values between true and calculated postmortem intervals were 0.78-0.82 in the five general methods based on rectal temperature. The multiple regression analysis produced a multiple correlation coefficient value of 0.89 and according to the error ranges of the PM intervals, 72% of the cases were estimated within the error of +/-1.0 h and 92% within +/-5.0 h. Although assessments of non-temperature based PM changes are mostly subjective and have a wide variation, the present study demonstrated a usefulness of non-temperature based PM changes in the estimation of PM intervals.

Adolescent↗
PubMed2001

Autistic features in Cohen syndrome: a preliminary report.

Cohen syndrome is a rare, genetic, connective-tissue disorder, with the genetic abnormality linked to chromosome 8q22. Its physical features (particular facial characteristics; body, limb, and visual abnormalities; height and weight problems) have been well documented but little is known about the psychological and behavioural development of individuals with the condition. Suggestion of a dual diagnosis of autism in a small minority of individuals led to a more detailed survey of parents belonging to the Cohen Syndrome Support Group, based in the UK. Thirty-three individuals, 18 males and 15 females, aged from 2 to 45 years (mean age 15 years) were involved in the study. Over half of the participants (n=19) showed a pattern of impairments in social and communication skills, together with rigid and stereotyped behaviours or interests that seemed to meet DSM-IV/ICD-10 criteria for autism. 'Autistic-type' problems were as common in females as in males. In almost all cases, parents had noted difficulties in their child before the child reached the age of 1 year. This study suffers from a number of methodological shortcomings including the fact that it was a postal survey, the sample size was small, and no standardized diagnostic or psychometric data were available. However, the incidence of social, communication, and behavioural problems would seem to warrant further research and a larger-scale study is planned in association with an independent investigation of physical and genetic characteristics in the same group of individuals.

Adolescent↗
PubMed1997

Intrathecal baclofen therapy for stiff-man syndrome and progressive encephalomyelopathy with rigidity and myoclonus.

We report on eight patients with stiff-man syndrome (SMS) or its "plus" variant, progressive encephalomyelopathy with rigidity and myoclonus (PERM) receiving intrathecal baclofen via pump. In six of the patients, follow-ups continued for approximately 2.5 to 6.5 years after pump implantation. Intrathecal baclofen was an effective last-resort alternative for patients who responded poorly to or did not tolerate oral antispasticity medications. General mobility increased, and spasms and rigidity were reduced; however, no complete remissions were observed either before or after pump implantation. PERM patients showed more severe and rapid progression of symptoms and more attacks of autonomic dysregulation than SMS patients. They also required higher doses and more rapid dosage increases. Complications of intrathecal baclofen therapy included spasm-induced rupture of the catheter, catheter dislocation causing radicular symptoms, and pump malfunction resulting in inaccurate dosage administration. Patients suffered fewer side effects with intrathecal baclofen than with oral medication, but overdose resulted in a transient, comalike state in one patient and sudden dosage reduction due to pump failure was fatal in another.

Adult↗
PubMed1997

[Pupillary abnormalities in a patient with clinically diagnosed corticobasal degeneration].

We report a 65-year-old woman, who suffered from clumsiness of the left hand for 6 years. Gait disturbance, body balance impairment and rigidity of the left arm appeared progressively. Anti-parkinsonian drugs such as 1-dopa, doroxidopa, amantadine and bromocriptine were ineffective. Magnetic resonance imaging showed brain atrophy, especially in the right fronto-parietal lobes. Positron emission tomography (18F-fluoro-2-deoxy-D-glucose) showed decreased glucose metabolism in the right cerebral cortex, putamen and thalamus. A diagnosis of corticobasal degeneration was made, based on the clinical manifestations, MRI and PET findings. She also showed anisocoria, vertical gaze palsy and abnormal pupillary reactions. Her left pupil showed an oval figure shifted from the center position. The pupils exhibited denervation supersensitivity in the 0.125% pilocarpine test. We consider that her pupillary abnormalities may be related to her midbrain lesion (midbrain corectopia) associated with corticobasal degeneration.

Aged↗
PubMed1999

Relationship of lesion location to clinical outcome following microelectrode-guided pallidotomy for Parkinson's disease.

The purpose of this study was to examine the relationship between lesion location and clinical outcome following globus pallidus internus (GPi) pallidotomy for advanced Parkinson's disease. Thirty-three patients were prospectively studied with extensive neurological examinations before and at 6 and 12 months following microelectrode-guided pallidotomy. Lesion location was characterized using volumetric MRI. The position of lesions within the posteroventral region of the GPi was measured, from anteromedial to posterolateral along an axis parallel to the internal capsule. To relate lesion position to clinical outcome, hierarchical multiple regression analysis was used. The variance in outcome measures that was related to preoperative scores and lesion volume was first calculated, and then the remaining variance attributable to lesion location was determined. Lesion location along the anteromedial-to-posterolateral axis within the GPi influenced the variance in total score on the Unified Parkinson's Disease Rating Scale in the postoperative 'off' period, and in 'on' period dyskinesia scores. Within the posteroventral GPi, anteromedial lesions were associated with greater improvement in 'off' period contralateral rigidity and 'on' period dyskinesia, whereas more centrally located lesions correlated with better postoperative scores of contralateral akinesia and postural instability/gait disturbance. Improvement in contralateral tremor was weakly related to lesion location, being greater with posterolateral lesions. We conclude that improvement in specific motor signs in Parkinson's disease following pallidotomy is related to lesion position within the posteroventral GPi. These findings are consistent with the known segregated but parallel organization of specific motor circuits in the basal ganglia, and may explain the variability in clinical outcome after pallidotomy and therefore have important therapeutic implications.

Aged↗
PubMed1985

Xenon contrast CT-CBF measurements in parkinsonism and normal aging.

Local cerebral blood flow (LCBF) and local tissue:blood partition, coefficient (L lambda) values were measured during CT scanning while patients with different types of Parkinson's syndrome (N = 14) inhaled a contrast mixture of 35-37 per cent stable xenon gas in oxygen. Single-compartment analysis fitted to infinity was used to calculate L lambda and LCBF values. Results were compared with results from normal age-matched volunteers (N = 24). Mean hemispheric (p less than 0.05) and subcortical (p less than 0.05) gray matter LCBF values were reduced in idiopathic Parkinson's disease (N = 11), compared to values from age-matched normals. Regionally, LCBF reductions included frontal (p less than 0.001), parietal cortex (p less than 0.05), caudate (p less than 0.05), lentiform nuclei (p less than 0.001) and thalamus (p less than 0.05) reductions. L lambda values were normal. Unilateral tremor and/or rigidity correlated directly with reduced LCBF in contralateral lentiform (p less than 0.01) and caudate (p less than 0.01) nuclei. In postencephalitic Parkinsonism (N = 1) LCBF reductions were diffuse, with normal L lambda values. In the akinetic form of Parkinsonism (N = 1) associated with lacunar infarcts, LCBF and L lambda reductions were patchy. In Parkinsonism following carbon monoxide poisoning (N = 1), LCBF values of gray and white matter were diffusely reduced and L lambda values were reduced in both pallidal regions. When dementia was present together with Parkinsonism (N = 3), LCBF reductions were more diffuse and severe. Dopaminergic deficiency correlated directly with reduced LCBF values, reflecting the severity of Parkinsonism.

Adult↗
PubMed1996

Drug therapy for Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disease characterized by tremor, rigidity, bradykinesia, and loss of postural reflexes. Although the agents available for symptomatic treatment now allow most parkinsonian patients to live a normal life-span, these patients become progressively unable to participate in social functions, perform activities of daily living, and work. Therapy for PD may be associated with many complications that contribute to these disabilities. For this reason, education is helpful for the patient newly diagnosed with PD. Over the past 6 years, three new medications (selegiline, pergolide, and controlled-release levodopa) have been approved for use in Parkinson's disease. Other agents now available for the treatment of psychiatric illness may also be helpful in selected cases of PD. With this in mind, we review the commonly prescribed drugs and outline a rational plan for treatment of parkinsonism.

Activities of Daily Living↗
PubMed1975

Comatose state maintained during eight years following a vascular ponto-mesencephalic lesion.

A 24-year-old man survived for 8 years after a vascular lesion of the pons and midbrain. During these years a subresponsive comatose state with neurological signs extending from the oculomotor nuclei to the trigeminal and facial nuclei levels was present. A decorticated type of rigidity, with bilateral paralysis of the limbs accompanied by pyramidal signs, was also present. The EEG during the first months showed slow activity which afterwards gradually changed towards fast and alpha activities, maintained in the course of the years. The pathological diagnosis was a fibrous endarteritis, mainly in the territory of the basilar and vertebral arteries. The pons and midbrain, presenting a large cystic infarct, were serially studied to determine the anatomical extent of the lesion. After reviewing other examples from the literature, the clinical features of our case are discussed. The evolution of the EEG is related to different structures of the ponto-mesencephalic region with different functional activities.

Adult↗
PubMed2001

Visual evoked potentials in Parkinson's disease-correlation with clinical involvement.

A total of 18 patients with Parkinson's disease were evaluated clinically and by transient checker-board VEP study. There were significant differences between bradykinesia (P<0.01), rigidity (P<0.02), and tremor (P<0.05) subscores of the more and less severely affected sides. There were no asymmetry of VEP latency or amplitude between the more and less severely affected sides by stimulation of the corresponding eye. There were no significant correlations between the VEP latency or amplitude and any of the clinical features except the bradykinesia scores. The bradykinesia scores on the more severely involved side (r: 0.57; P=0.014) and less severely involved side (r: 0.82; P=0.00003) showed medium to high degree positive correlations with VEP amplitudes by stimulation of the corresponding eye. By studying monocular fullfield responses our data can only suggest that there is no prechiasmal asymmetry. The positive correlation between the VEP amplitude and bradykinesia score might indicate that D2 receptors dominate in the retina.

Adult↗
PubMed2006

Stimulation of the caudal zona incerta is superior to stimulation of the subthalamic nucleus in improving contralateral parkinsonism.

Deep brain stimulation (DBS) has an increasing role in the treatment of idiopathic Parkinson's disease. Although, the subthalamic nucleus (STN) is the commonly chosen target, a number of groups have reported that the most effective contact lies dorsal/dorsomedial to the STN (region of the pallidofugal fibres and the rostral zona incerta) or at the junction between the dorsal border of the STN and the latter. We analysed our outcome data from Parkinson's disease patients treated with DBS between April 2002 and June 2004. During this period we moved our target from the STN to the region dorsomedial/medial to it and subsequently targeted the caudal part of the zona incerta nucleus (cZI). We present a comparison of the motor outcomes between these three groups of patients with optimal contacts within the STN (group 1), dorsomedial/medial to the STN (group 2) and in the cZI nucleus (group 3). Thirty-five patients with Parkinson's disease underwent MRI directed implantation of 64 DBS leads into the STN (17), dorsomedial/medial to STN (20) and cZI (27). The primary outcome measure was the contralateral Unified Parkinson's Disease Rating Scale (UPDRS) motor score (off medication/off stimulation versus off medication/on stimulation) measured at follow-up (median time 6 months). The secondary outcome measures were the UPDRS III subscores of tremor, bradykinesia and rigidity. Dyskinesia score, L-dopa medication reduction and stimulation parameters were also recorded. The mean adjusted contralateral UPDRS III score with cZI stimulation was 3.1 (76% reduction) compared to 4.9 (61% reduction) in group 2 and 5.7 (55% reduction) in the STN (P-value for trend <0.001). There was a 93% improvement in tremor with cZI stimulation versus 86% in group 2 versus 61% in group 1 (P-value = 0.01). Adjusted 'off-on' rigidity scores were 1.0 for the cZI group (76% reduction), 2.0 for group 2 (52% reduction) and 2.1 for group 1 (50% reduction) (P-value for trend = 0.002). Bradykinesia was more markedly improved in the cZI group (65%) compared to group 2 (56%) or STN group (59%) (P-value for trend = 0.17). There were no statistically significant differences in the dyskinesia scores, L-dopa medication reduction and stimulation parameters between the three groups. Stimulation related complications were seen in some group 2 patients. High frequency stimulation of the cZI results in greater improvement in contralateral motor scores in Parkinson's disease patients than stimulation of the STN. We discuss the implications of this finding and the potential role played by the ZI in Parkinson's disease.

Aged↗
PubMed2005

Pathophysiology of motor fluctuations in Parkinson's disease.

Loss of dopamine neurons in Parkinson's disease (PD) initiates a complex stream of effects that results in the development of tremor, bradykinesia, and rigidity. While levodopa remains the most effective drug for the symptomatic treatment of PD, its chronic administration is associated with the development of motor fluctuations and dyskinesias. The risk of developing motor fluctuations has been linked to disease severity, dosage of levodopa, and the age of the patient. A recent body of preclinical data has demonstrated that alterations in dopaminergic tone as well as in treatment patterns results in cellular adaptations, including alterations in gene expression. This body of preclinical data suggests that nonphysiological, pulsatile stimulation of dopamine receptors induces the development of motor fluctuations and dyskinesias and raises the possibility that nonpulsatile stimulation of dopamine receptors (continuous dopaminergic stimulation) might induce fewer fluctuations. We discuss the theory of continuous dopaminergic stimulation and its implications for the management of motor fluctuations in patients with advanced and early PD.

Adaptation, Physiological↗
PubMed1997

Neurological signs and frontal white matter lesions in vascular parkinsonism. A clinicopathologic study.

BACKGROUND AND PURPOSE: The clinical characteristics and the pathological lesions of so-called vascular parkinsonism (VP) are still debatable. The purpose of this study was to define the core signs and symptoms and assess the cerebrovascular lesions in pathologically confirmed VP. METHODS: In the present study, VP was defined as the presence of parkinsonism and pathological evidence of cerebrovascular lesions but no depigmentation or Lewy bodies at the substantia nigra. We compared the clinical signs and symptoms of 24 VP patients with those of 30 age-matched patients with pathologically confirmed Parkinson's disease. We compared the brain pathology in VP patients with that in 22 age-matched patients with Binswanger's disease (BD) who had no parkinsonism according to clinical records. RESULTS: VP was characterized clinically by a short-stepped or frozen gait, lead-pipe rigidity, absence of resting tremor, and negative response to levodopa. Half or more of VP patients demonstrated pyramidal tract signs and pseudobulbar palsies. There was no significant difference in the extent of vascular lesions at the basal ganglia between patients with VP and with BD without parkinsonism. The extent of frontal white matter pallor tended to be less broad in VP than in BD without parkinsonism. In VP patients, the number of oligodendrocytes in the frontal white matter was significantly less than that in age-matched normal control subjects and significantly more than in those with BD. CONCLUSIONS: The core signs and symptoms of autopsy-proved VP differ from those of typical Parkinson's disease, and most VP patients had diffuse cerebral white matter lesions as well as basal ganglia lesions. VP might be related to frontal white matter lesions.

Aged↗
PubMed1986

Bromocriptine: long-term low-dose therapy in Parkinson's disease.

Low-dose bromocriptine therapy (average dose 14.5 mg/day at 2 years) produced significant improvement in 25 of 39 parkinsonian patients. Bradykinesia was less in de novo subjects; tremor and rigidity improved most in the levodopa subjects. Five of six patients improved after a low-dose bromocriptine drug "holiday." After the addition of bromocriptine any reductions in levodopa dosage were small, with repeated cuts made gradually over months preventing the deterioration commonly seen with larger sudden reductions in levodopa dosage. Five patients withdrew because of intolerable adverse effects, two because of worsening response. Adverse effects were mild and generally dose dependent, and in some patients they disappeared without reduction in continuing bromocriptine therapy. Eighty percent of those who tolerated bromocriptine maintained response over 2 years. Bromocriptine did not induce dyskinesia, the wearing-off response, or the on-off phenomenon in de novo subjects and was used as a first choice drug in these parkinsonian patients. Best results were obtained from a combination of bromocriptine and levodopa.

Adult↗
PubMed2005

Gender and the Parkinson's disease phenotype.

OBJECTIVES: To determine whether there are gender differences in the Parkinson's disease (PD) phenotype using a large clinic-based cohort. METHODS: We examined gender differences in demographic, historical and clinical characteristics in a consecutive clinical series of 1,264 individuals diagnosed with PD. RESULTS: The majority of individuals in the sample were male (67 %). Comparative analyses showed males and females were not significantly different on most demographic and historical characteristics. For both genders, the mean age and the mean age at symptomatic onset were about 70 and 63 years, respectively and, thus, disease duration was not significantly different between genders. The proportion of individuals with a positive family history of PD (15 %) was similar for both genders. A positive history of depression was significantly higher in females (35 % vs. 24 %). The UPDRS instability score was significantly worse among females, whereas the rigidity score was significantly worse for males. Females showed significantly worse ADL capacity and a more advanced H&Y stage. The proportion of individuals receiving antiparkinsonian medication (about 66 %) and time between the last dose and the clinical evaluation (about 4 hours) was similar for both genders. There was a trend for lower daily levodopa equivalence dosage and more severe dyskinesia score among females but these differences did not reach statistical significance after Bonferroni correction. CONCLUSIONS: The majority of comparisons tended to highlight the commonalities in the PD phenotype between genders, particularly in reference to historical and early disease stage characteristics. However, gender may be an important factor related to the expression of PD features during the symptomatic disease course.

Activities of Daily Living↗
PubMed1995

Effect of parkinsonian signs and symptoms of bilateral subthalamic nucleus stimulation.

In monkeys rendered parkinsonian, lesions and electrical stimulation of the subthalamic nucleus reduce all major motor disturbances. The effect of electrical stimulation of the subthalamic nucleus was assessed in three patients with disabling akinetic-rigid Parkinson's disease and severe motor fluctuations. Quadripolar electrodes connected to a pulse generator were implanted in the subthalamic nuclei on both sides. Patients were evaluated with the unified Parkinson's disease rating scale and timed motor tests. 3 months after surgery, activities of daily living scores had improved by 58-88% and motor scores by 42-84%. This improvement was maintained for up to 8 months in the first patient operated upon. One patient was confused for 2 weeks after surgery, and another developed neuropsychological impairment related to a thalamic infarction which improved over 3 months. In one patient, stimulation could induce ballism that was stopped by reduction of stimulation. This is the first demonstration in human beings of the part played by the subthalamic nuclei in the pathophysiology of Parkinson's disease.

Electric Stimulation Therapy↗
PubMed1999

Incomplete nigrostriatal dopaminergic cell loss and partial reductions in striatal dopamine produce akinesia, rigidity, tremor and cognitive deficits in middle-aged rats.

The present study was conducted to determine if the full array of parkinsonian symptoms could be detected in rats with nigrostriatal cell loss and striatal dopamine depletions similar to levels reported in the clinical setting, and to determine if older rats exhibit more robust parkinsonian deficits than younger rats. Young (2 months old) and middle-aged (12 months old) rats received bilateral striatal infusions of 6-OHDA, over the next 3 months they were assessed with a battery of behavioral tests, and then dopaminergic nigrostriatal cells and striatal dopamine and DOPAC levels were quantified. The results of the present study suggest that: (1) the full array of parkinsonian symptoms (i.e. akinesia, rigidity, tremor and visuospatial cognitive deficits) can be quantified in rats with incomplete nigrostriatal dopaminergic cell loss and partial reductions in striatal dopamine levels (2) parkinsonian symptoms were more evident in middle-aged rats with 6-OHDA infusions, and (3) there was evidence of substantial neuroplasticity in the older rats, but regardless of the age of the animal, endogenous compensatory mechanisms were unable to maintain striatal dopamine levels after rapid, lesion-induced nigrostriatal cell loss. These results suggest that using older rats with nigrostriatal dopaminergic cell loss and reductions in striatal dopamine levels similar to those in the clinical condition, and measuring behavioral deficits analogous to parkinsonian symptoms, might increase the predictive validity of pre-clinical rodent models.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Corticobasal degeneration. A unique pattern of regional cortical oxygen hypometabolism and striatal fluorodopa uptake demonstrated by positron emission tomography.

Corticobasal degeneration presents with an asymmetric akinetic-rigid syndrome, apraxia and combinations of supranuclear gaze palsy, myoclonus, and an alien limb. Six patients aged 59-77 yrs, diagnosed on clinical criteria as having corticobasal degeneration, have been studied with positron emission tomography using tracers of dopamine storage capacity and oxygen metabolism. Striatal 18F-6-fluorodopa uptake was reduced in an asymmetric pattern, caudate and putamen being involved in all cases. Uptake into medial frontal cortex was also impaired. Regional cortical oxygen metabolism was most significantly depressed in the superior and posterior temporal, inferior parietal, and occipital associated cortices. Within the frontal lobe, the hypometabolism was chiefly posterior. This unique combination of regional hypometabolism and disruption of the nigrostriatal system is discussed in relation to the clinical features of the disease and is compared with reported findings in other disorders of cognition and movement.

Aged↗
PubMed1998

[McKay operation in the correction of rigid clubfoot].

For the evaluation of the result from McKay operation in the correction of rigid clubfoot, 71 patients (103 feet) were followed up postoperatively for 2 to 9 years. According to the criteria concerning the functional recovery of the foot, the external appearance of the foot after correction and the roentgenographic findings, the result was evaluated as excellent in 55 patients (78 feet), good in 11 patients (16 feet), fair in 5 patients (9 feet) and with no recurrence. It was considered that the favorable time for operation was when the child being 6 to 18 months old. In 7 patients (12 feet), there were morphological changes of the calcaneal and navicular bones in 12 feet, limitation of ankle movement in 9 patients and resultant flatfoot deformity in 5 patients (7 feet). The factors influencing the functional recovery of the foot and the relationship between the corrective result and the age of patient when the operation being given were discussed in details.

Child↗