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Background: Response fluctuations and dyskinesias develop during the use of both levodopa (LD) and dopamine agonists (DA), but may not be equally disabling., Objective: To compare the risk and time of onset of disabling response fluctuations and dyskinesias (DRFD) among patients with Parkinson's disease (PD) who were initially treated with either LD or DA., Methods: Open cohort study of all consecutive de-novo PD patients in routine clinical practice, included over a period of 15 years (median follow-up: 8.1 years, range 1.1-17.7), since embarking on LD or DA. Older patients and patients with more severe PD were started on LD (n = 77), younger patients on a DA (n = 50). Therapy was adjusted according to generally accepted guidelines. The primary endpoints were: the onset of response fluctuations, dyskinesias, and the moment when these complications became disabling (DRFD)., Results: LD-starters developed response fluctuations 0.8 years earlier than DA-starters (p = 0.07), while dyskinesias appeared around 2.5 years earlier (p = 0.003). However, the risk and time of onset of DRFD did not differ statistically between the groups (LD-starters: 60% , median interval 7.3 years, DA-starters: 52% , 6.1 years, p = 0.63). DA-starters displayed a 0.19 points lower adjusted mean improvement in motor scores than LD-starters (p = 0.002). Adjustments for age and severity of PD at start of dopaminergic therapy did not change these results., Conclusions: In routine clinical practice, the risk and time of onset of DRFD is comparable for LD-starters versus DA-starters, but motor functioning is worse in DA-starters. These results support the use of LD as initial therapy for PD.

Spontaneous paresthesia of the mental nerve is considered an ominous clinical sign. Mental nerve paresthesia has also been referred to as numb chin syndrome. Several potentially different factors have been investigated for their role in interfering with the inferior alveolar nerve (IAN) and causing mental nerve neuropathy. In the present case, the patient had an elongated calcified styloid process that we hypothesized had caused IAN irritation during mandibular movement. This eventually resulted in progressive loss of sensation in the mental nerve region. To our knowledge, this dynamic irritation, with complete recovery after resection of the styloid process, has not been previously reported., (Copyright © 2014 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Early-onset Parkinson's disease (EOPD) has been associated with recessive mutations in parkin (PARK2). About half of the mutations found in parkin are genomic rearrangements, i.e., large deletions or duplications. Although many different rearrangements have been found in parkin before, the exact breakpoints involving these rearrangements are rarely mapped. In the present study, the exact breakpoints of 13 different parkin deletions/duplications, detected in 13 patients out of a total screened sample of 116 EOPD patients using Multiple Ligation Probe Amplification (MLPA) analysis, were mapped using real time quantitative polymerase chain reaction (PCR), long-range PCR and sequence analysis. Deletion/duplication-specific PCR tests were developed as a rapid and low cost tool to confirm MLPA results and to test family members or patients with similar parkin deletions/duplications. Besides several different deletions, an exon 3 deletion, an exon 4 deletion and an exon 7 duplication were found in multiple families. Haplotype analysis in four families showed that a common haplotype of 1.2 Mb could be distinguished for the exon 7 duplication and a common haplotype of 6.3 Mb for the deletion of exon 4. These findings suggest common founder effects for distinct large rearrangements in parkin.

Chorea may occur as part of the symptomatology of acute stroke; it occasionally also may be delayed or progressive. Patients with vascular-related chorea typically present with an acute or subacute onset of chorea of one side of the body (hemichorea), contralateral to the lesion. Cerebrovascular disease is the most common cause of sporadic chorea. Lesions are most frequently found in the thalamus and lentiform nucleus, and less often in subthalamic nucleus. The differential diagnosis of choreic syndromes relies not so much on differences in the phenomenology of the hyperkinesia but the age at onset, mode of onset, time course, family history, drug use, distribution of chorea in the body, and presence of accompanying neurological findings. Magnetic resonance imaging is preferred to demonstrate the presence of strategic small lesions in regions that are difficult to image with computed tomography, such as the globus pallidus, thalamus, and subthalamic nucleus. Although the prognosis of hemichorea can be benign, the long-term prognosis is not specifically determined by the hemichorea but by the long-term prognosis of stroke patients. Symptomatic treatment with antichoreic drugs may be necessary in the acute phase. Surgery is rarely indicated to treat vascular chorea., (Copyright © 2011 Elsevier B.V. All rights reserved.)

After more than 40 years of clinical use, levodopa (LD) remains the gold standard of symptomatic efficacy in the drug treatment of Parkinson's disease (PD). Compared with other available dopaminergic therapies, dopamine replacement with LD is associated with the greatest improvement in motor function. Long-term treatment with LD is, however, often complicated by the development of various types of motor response oscillations over the day, as well as drug-induced dyskinesias. Motor fluctuations can be improved by the addition of drugs such as entacapone or monoamine oxidase inhibitors, which extend the half-life of levodopa or dopamine, respectively. However, dyskinesia control still represents a major challenge. As a result, many neurologists have become cautious when prescribing therapy with LD. This review summarizes the available evidence regarding the use of LD to treat PD and will also address the issue of LD delivery as a critical factor for the drug's propensity to induce motor complications.

Parkinsonism is a syndrome that features bradykinesia (slowness of the initiation of voluntary movement) and at least 1 of the following conditions: rest tremor, muscular rigidity, or postural instability. Criteria for the clinical diagnosis of vascular parkinsonism (VP) have been proposed, which are derived from a postmortem examination study. Computed tomography and magnetic resonance imaging can support this clinical diagnosis with positive imaging findings. Dopamine transporter single-photon emission computed tomography may also be of help to distinguish VP from Parkinson disease and other parkinsonisms.

We present a 36-year-old Dutch woman who suffered from a progressive form of cerebellar ataxia since school age. In her childhood she was diagnosed with Friedreich's ataxia. Genetic analysis of the frataxin gene at 34 years of age, however, had revealed no abnormal GAA triplet expansion. We identified two point mutations in the alpha-tocopherol transport protein (alpha-TTP) gene on chromosome 8q13, and the diagnosis ataxia with isolated vitamin E deficiency (AVED) was made. This report illustrates the diagnosis AVED and its relation to vitamin E metabolism. It is important to evaluate previously made diagnoses when newly developed tests can be performed for confirmation.

Background: Although movement disorders that occur following a stroke have long been recognised in short series of patients, their frequency and clinical and imaging features have not been reported in large series of patients with stroke., Methods: We reviewed consecutive patients with involuntary abnormal movements (IAMs) following a stroke who were included in the Eugenio Espejo Hospital Stroke Registry and they were followed up for at least one year after the onset of the IAM. We determined the clinical features, topographical correlations, and pathophysiological implications of the IAMs., Results: Of 1500 patients with stroke 56 developed movement disorders up to one year after the stroke. Patients with chorea were older and the patients with dystonia were younger than the patients with other IAMs. In patients with isolated vascular lesions without IAMs, surface lesions prevailed but patients with deep vascular lesions showed a higher probability of developing abnormal movements. One year after onset of the IAMs, 12 patients (21.4%) completely improved their abnormal movements, 38 patients (67.8%) partially improved, four did not improve (7.1%), and two patients with chorea died. In the nested case-control analysis, the patients with IAMs displayed a higher frequency of deep lesions (63% v 33%; OR 3.38, 95% CI 1.64 to 6.99, p<0.001). Patients with deep haemorrhagic lesions showed a higher probability of developing IAMs (OR 4.8, 95% CI 0.8 to 36.6)., Conclusions: Chorea is the commonest movement disorder following stroke and appears in older patients. Involuntary movements tend to persist despite the functional recovery of motor deficit. Deep vascular lesions are more frequent in patients with movement disorders.

Carcinomatous meningitis is extremely rare in cervical cancer. The diagnosis of carcinomatous meningitis is a difficult one when clinical symptoms are limited and radiographic imaging is normal. Demonstration of malignant cells in the cerebrospinal fluid remains the gold standard to establish the diagnosis. For patients without bulky disease who can be treated with radiotherapy, standard treatment for carcinomatous meningitis is chemotherapy, which may be administered intrathecally. Despite the poor prognosis, treatment may result in effective palliation. We describe a 54-year-old patient who was diagnosed with carcinomatous meningitis in the course of metastatic cervical cancer and who responded to administration of intrathecal methotrexate.

We investigated whether administration of the catechol-O-methyl transferase (COMT) inhibitor entacapone, at doses of 200 mg and 400 mg, alters the pharmacokinetics of apomorphine in Parkinson's disease patients experiencing severe motor fluctuations. In addition, the pharmacodynamics and safety of entacapone and apomorphine coadministration in these patients were examined. The study followed a three-sequence, three-period, crossover design. Patients were randomly assigned to one of three sequences that included single oral doses of entacapone 200 mg, entacapone 400 mg, and placebo in a predefined order. On 3 separate test days, study treatment was administered before apomorphine. The study evaluations (pharmacokinetics, tapping test, and dyskinesia evaluation [Abnormal Involuntary Movements Scale - AIMS]) were performed on these days. Furthermore, Unified Parkinson Disease Rating Scale (UPDRS) scores were evaluated at baseline and study end. Pharmacokinetic parameters for apomorphine (C(max), AUC, t(max), t(1/2)) were unchanged by the administration of entacapone, and changes in both the tapping test and AIMS score were similar with all treatments (entacapone 200 mg, entacapone 400 mg, and placebo). There was no significant difference in mean total UPDRS scores between baseline and study end. The administration of entacapone did not change the pharmacokinetic or pharmacodynamic effects of apomorphine in these patients or prolong the clinical effect of apomorphine. Thus, apomorphine may be safely administered to patients receiving therapy with levodopa and entacapone, providing a useful addition to treatment for patients with advanced Parkinson's disease.

Vascular parkinsonism (VP) is difficult to diagnose with any degree of clinical certainty. We investigated the importance of macroscopic cerebral infarcts and pathological findings associated with microscopic "small vessel disease" (SVD) in the aetiology of VP. The severity of microscopic SVD pathology (perivascular pallor, gliosis, hyaline thickening, and enlargement of perivascular spaces) and the presence of macroscopically visible infarcts were assessed in 17 patients with parkinsonism and no pathological evidence of either Parkinson's disease or any histopathological condition known to be associated with a parkinsonian syndrome, and compared with age-matched controls. Microscopic SVD pathology was significantly more severe in the parkinsonian brains. Most patients presented with bilateral bradykinesia and rigidity together with a gait disorder characterised predominantly by a shuffling gait. Four patients presented acutely with hemiparesis and then progressed to develop a parkinsonian syndrome. They could be distinguished from the remaining VP patients by the presence at autopsy of macroscopically visible lacunar infarcts in regions where contralateral thalamocortical drive might be reduced. The clinical features at presentation varied according to the speed of onset and the underlying vascular pathological state. New clinical criteria for a diagnosis of VP are proposed based on the clinicopathological findings of this study., (Copyright 2004 Movement Disorder Society)

Objective: To determine whether a positive L-dopa response in vascular parkinsonism (VP) is correlated with the presence of nigrostriatal pathology due to either vascular damage or neuronal cell loss., Methods: Seventeen patients with pathologically confirmed VP were selected from the pathological collection of the Queen Square Brain Bank for Neurological Disorders, and their L-dopa response during life was compared with the presence of macroscopic vascular damage in the nigrostriatal pathway and microscopic substantia nigra cell loss., Results: Ten of the twelve patients with a good or excellent response had macroscopic infarcts or lacunae caused by enlarged perivascular spaces in the basal ganglia or microscopic neuronal cell loss in the substantia nigra. In contrast, only one of the five patients with a moderate or no response had lacunae in the putamen, and none had lacunar infarcts or substantia nigra cell loss., Conclusion: These results suggest that a substantial number of patients with clinically suspected VP may respond with benefit to dopaminergic therapy, especially those with lesions in or close to the nigrostriatal pathway.

We investigated whether [(123)I]-beta-CIT and single-photon emission computed tomography (SPECT) imaging distinguishes patients with clinically suspected vascular parkinsonism (VP) from patients with idiopathic Parkinson's disease (PD). [(123)I]beta-CIT SPECT is a sensitive marker of dopaminergic degeneration, and the degree of striatal binding reduction in PD correlates with disease severity. Thirteen patients who fulfilled rigid clinical criteria for VP (mean +/- S.D.: age, 76.5 +/- 5.3 years; disease duration, 3.6 +/- 2.8 years), 20 PD patients (age, 66.2 +/- 9.5 years; disease duration, 4.3 +/- 2.7 years), and 30 healthy persons (age, 44.6 +/- 19.2 years) underwent [(123)I]beta-CIT SPECT imaging. Age-corrected striatal beta-CIT binding was reduced on average by 40.8% in PD but was near normal in the VP group (mean reduction, 1.2%). This difference was statistically significant (Z = 4.68; P < 0.001). The left-right asymmetry of striatal beta-CIT binding was significantly increased in the PD group compared with normal controls and the VP group (F(2) = 17.4, P <0.001). Moreover, putamen-caudate nucleus ratios were significantly reduced in PD compared with both VP patients and healthy controls (F(2) = 65.5, P < 0.001). Whole striatal beta-CIT binding was more than one standard deviation above the mean PD values in all but one of the individual VP patients. Our findings suggest that the presynaptic dopaminergic deficits seen in PD are absent in most patients with VP. [(123)I]beta-CIT SPECT imaging may be useful to help distinguish between PD and VP patients during life., (Copyright 2002 Movement Disorder Society)

Objectives: To investigate whether the conventional and quantitative EEGs of patients with vascular parkinsonism (VP) differ from those of idiopathic Parkinson's disease (PD) patients., Material and Methods: The EEGs of 13 patients with vascular parkinsonism and 14 patients with idiopathic Parkinson's disease were scored on a simple scale regarding aspects of conventional EEG variables. Alpha band power asymmetry and EEG slowing (increased delta and theta power) were calculated by the neurometrics method of quantitative EEG data evaluation., Results: Analysis of both conventional and quantitative EEG data shows that VP patients had significantly less EEG slowing than PD patients., Conclusion: This study shows that the EEG in a group of patients with vascular parkinsonism differ from a patient group with idiopathic Parkinson's disease. Our results indicate that VP patients are not PD patients with subcortical vascular lesions, because then they would have had at least as much EEG slowing as PD patients.

Until now the clinical criteria for the diagnosis of vascular parkinsonism (VP) have been disputed. The purpose of the present study is to investigate whether quantitative gait analysis can differentiate between the gait pattern of patients with VP and the gait pattern of patients with idiopathic Parkinson's disease (PD). Twelve patients with VP, 12 patients with PD, and 10 neurologically nondiseased controls were examined by quantitative gait analysis. Patients with VP, having a similar gait velocity and stride length, showed relatively preserved arm swing with markedly more anteflexion in the shoulder on the forward sway of the arm swing than patients with PD. Patients with VP also showed less flexion dystonic posture of the elbow, hip, knee, and trunk than did patients with PD. There was no significant difference in the excursions and coordination of arm swing in the patients with VP compared with the control group. Both patient groups showed reduced leg movements, reduced hip extension, and reduced knee flexion and extension as compared with the controls.

To determine whether MRI can reveal more vascular lesions in patients clinically suspected of having vascular parkinsonism, we compared 15 such patients with 15 patients who had idiopathic Parkinson's disease and 10 hypertensive controls. Patients with suspected vascular parkinsonism had significantly more subcortical lesions than those with Parkinson's disease or hypertension. The cutoff point that best distinguished patients with suspected vascular parkinsonism from patients with Parkinson's disease was a 0.6% level of lesioned brain tissue volume. There were two types of vascular parkinsonism: one had an acute onset and lesions located in the subcortical gray nuclei (striatum, globus pallidus, thalamus); the other had an insidious onset and lesions diffusely distributed in the watershed areas.

Purpose: To describe an MR imaging quantification method for estimation of total volumes of both white and gray matter subcortical lesions and ventricular cerebrospinal fluid (CSF) in the living human brain, and to determine the method's reliability., Methods: In 12 subjects, total subcortical lesion and ventricular CSF volumes were estimated using systematic sampling. Systematic sampling was performed on equidistant MR sections using a counting grid with systematically ordered intersection points. The grid was randomly positioned on each consecutive MR section. Each grid intersection point hitting the structure of interest represents a fixed known volume dependent on grid intersection point distance and the sum of the section thickness and section gap., Results: Total volume estimation of subcortical lesion and ventricular CSF takes 15 and 5 minutes per subject, respectively. Coefficients of error of the individual volume estimates ranged from .01 to .13 and are negligible to the coefficients of the group mean (range, .70 to .89). For subcortical lesion volume, the random intraobserver error yielded .04 and for ventricular CSF .02; the random interobserver error amounted to .11 and .04, respectively; and the systematic interobserver error was .15 and .04, respectively., Conclusion: The method described here for subcortical lesion and ventricular CSF volume estimation is accurate, reliable, valid, and fast.

Up to now the existence of "vascular parkinsonism" has been doubtful because conclusive clinicopathologic studies are lacking. The objective of the present magnetic resonance spectroscopy (MRS) study is to detect metabolic signs as a reflect of ischemic lesions which could be responsible for the clinical features of vascular parkinsonism. Proton MRS of the brain was performed in 12 patients suspected of vascular parkinsonism on clinical grounds and ischemic score, and in a control group of 15 patients with idiopathic Parkinson's disease. The MR spectra were measured in the striatum and deep white matter. MRS did not demonstrate metabolic evidence for the existence of ischemia (elevated lactate) or cell loss (decreased N-acetyl-aspartate levels) in patients suspected of vascular parkinsonism. Several explanations for our findings are discussed.

Three putative risk factors to the pathogenesis of end-of-dose-related fluctuations--severity of Parkinson's disease (PD), duration of PD, and duration of levodopa therapy--were evaluated in 39 patients with PD by measuring response duration and response magnitude to a single levodopa dose. After discontinuing levodopa therapy for 12 hours, the motor status of each patient was assessed before a single dose of 100 mg of levodopa plus 25 mg of decarboxylase inhibitor was given and at five 45-minute intervals thereafter. Multiple regression analysis showed that the response duration was best predicted by the severity of PD. The response magnitude was significantly correlated both to the duration of PD and to the duration of levodopa therapy. It is argued, however, that the response magnitude was predicted by the duration of levodopa therapy. Our results are in accordance with those of other recent studies and indicate that variances in levodopa response duration and in levodopa response magnitude are caused by their own differential risk factor.

Fifty four patients with idiopathic Parkinson's disease receiving levodopa therapy were studied. Thirty three of these patients displayed peak-dose dyskinesia. Neither the duration of Parkinson's disease nor the duration of levodopa therapy discriminated between patients with and patients without peak-dose dyskinesia. Consequently, these criteria could not determine whether the first appearance of peak-dose dyskinesia depends on the duration of Parkinson's disease--a factor that is related to the severity of the disease--or on the duration of levodopa therapy. A subgroup of nineteen patients with unilateral or unequivocally asymmetrical peak-dose dyskinesia was examined 12 hours after withdrawal of levodopa. A levodopa testdose provoked unilateral or unilateral preponderant peak-dose dyskinesia which always involved the most severely affected side and which also happened to be the side of onset of the disease. This demonstrates that the severity of Parkinson's disease is the main risk factor for peak-dose dyskinesia.