Urinary profile of catecholamines and metabolites in Parkinson patients with deep brain stimulation.

BACKGROUND AND PURPOSE: Deep brain stimulation of the subthalamic nucleus (DBS-STN) is thought to continuously alter the activity of STN neurons in Parkinson's disease (PD). A chronic decrease in the levodopa dose with continuous STN stimulation may induce plastic neuronal changes. OBJECTIVE: The objective of this work was to study urinary excretion of catecholamines in patients with PD before and after DBS-STN. METHODS: Twenty-three patients were submitted to DBS-STN, and evaluated before and after surgery with respect to catecholamines and metabolites in 24-h urine measured by high-performance liquid chromatography with electrochemical detection. RESULTS: Of the 23 patients evaluated, a significant decrease of about 60% in the urinary excretion of L-3,4-dihydroxyphenylalanine (L-DOPA; in nmol/mg creatinine/24 h) was observed 1 week after DBS-STN. Moreover, in 17 patients with a follow-up of 8 weeks after surgery, there was a further 50% decrease in urinary L-DOPA levels, dropping to about 75% of the values before surgery. There was also a significant decrease in dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) levels 1 week after DBS-STN that was no longer present 8 weeks after. A significant increase in the DA/l-DOPA ratio was observed 1 week after surgery, with a further increase 8 weeks after surgery. CONCLUSION: After DBS-STN, the DA/l-DOPA ratio, an indirect measure of DA synthesis, increased. These results show that DBS-STN may improve the efficacy of oral levodopa.

How do cognitive and axial motor signs correlate in Parkinson's disease? A 6-year prospective study.

Impairment of Parkinson's disease (PD) axial motor signs (AMS) has been described as a risk factor for dementia. Executive dysfunction is an important feature in recently proposed clinical diagnostic criteria for PD dementia. To clarify the relationship between AMS progression and executive cognitive performance, we conducted a 6-year prospective study in PD patients without AMS impairment at baseline. A hospital-based cohort of PD patients (n = 24) without dementia, in the initial motor stage (Hoehn-Yahr < or = 2), and matched controls (n = 20) were followed prospectively over a 6-year period. Neuropsychological tests were performed in both groups, and motor function (including AMS: speech, gait, postural instability) was evaluated in the PD group. The PD group had a significantly higher decline in neuropsychological test scores than did the controls. Most of the neuropsychological and motor decline occurred in the last 4 years. In UPDRS III, progression of AMS and especially speech were the most important motor variables related to dementia. There was a correlation between speech impairment progression and declines in MMSE (r = -0.598, p = 0.002), Clock Drawing (r = -0.671, p < 0.001), Semantic Verbal Fluency (r = -0.435, p = 0.034), Alternating Sequences (r = 0.497, p = 0.014), and Raven's Coloured Progressive Matrices (r = -0.735, p < 0.001). PD patients with higher speech impairment progression showed more rapid declines in some neuropsychological tests. Further studies are needed to clarify the different roles of speech, gait and postural instability on the initial phases of cognitive dysfunction.

Transient disabling dyskinesias: a predictor of good outcome in subthalamic nucleus deep brain stimulation in Parkinson's disease.

We report 5 of 75 (6.6%) patients with Parkinson's disease (PD) submitted to subthalamic nucleus deep brain stimulation (STN-DBS) who developed transient disabling dyskinesias immediately after surgery. Dyskinesias persisted despite levodopa withdrawal, cessation or reduction of stimulation, and resolved spontaneously in a maximum period of 12 weeks without the need to change stimulation active contact. Compared to the rest of our PD patients submitted to STN-DBS, the dyskinesia group needed a lower levodopa-equivalent daily dosage (LEDD) over the time of follow-up. A microlesion in the STN, probably concealed in cerebral MRI by the electrode-related artifact, could have been involved in the etiopathology of our patients' symptoms. The presence of transient disabling dyskinesia in PD patients immediately after STN-DBS might be a predictor of good outcome as measured by a decrease in the LEDD needed.

SANDO: two novel mutations in POLG1 gene.

Sensory ataxia with neuropathy, dysarthria and ophthalmoparesis represent the clinical triad of SANDO, a specific mitochondrial phenotype first reported in 1997 in association with multiple mitochondrial DNA deletions and mutations in POLG1 or more rarely in the C10orf2 (twinkle-helicase) gene. We report a 44-year-old man with SANDO who harboured two novel mutations (P648R/R807C) in the POLG1 gene.

Effects of metformin on the body composition in subjects with risk factors for type 2 diabetes.

OBJECTIVES: To measure the effect of metformin on the body composition, insulin resistance and sensitivity in subjects with risk factors for type 2 diabetes mellitus (type 2 DM). DESIGN: Placebo-controlled clinical trial. MATERIAL AND METHODS: Twenty-three subjects with risk factors for type 2 DM were randomly assigned to receive 850 mg of metformin or a placebo twice a day for 2 months. Before and after the treatment, the body mass index and waist/hip ratio were calculated, the body composition was measured through bioelectric impedance and the fasting levels of blood glucose, insulin, triglycerides and cholesterol were measured. The level of insulin resistance was calculated by the homeostatic model and the level of sensitivity by the quantitative insulin sensitivity check index method. The Wilcoxon rank test was used. RESULTS: Twenty-one subjects completed the study, 12 of the metformin group and nine of the placebo group. In the metformin group, there was a decrease in fat weight from 25.9 +/- 9.4 to 20.8 +/- 9.2 kg, p < 0.01, an increase in lean weight from 57.05 +/- 13.6 to 61.9 +/- 16.5 kg, p < 0.01, an increase in basal metabolism from 1735 +/- 413 to 1878 +/- 505 calories/day, p < 0.05 and an increase in body water, p < 0.05. There was no significant decrease in insulin resistance. In the placebo group, the blood glucose increased from 84.7 +/- 13 to 96.7 +/- 16 mg/dl, p < 0.05. There were no significant modifications in lipids. CONCLUSIONS: The administration of metformin for 2 months improves the parameters of body composition and insulin dynamics in subjects with risk factors for type 2 DM.

Delay in hospital admission of patients with cerebral vein and dural sinus thrombosis.

Factors influencing early hospital admission have been described for several stroke types but not for cerebral vein and dural sinus thrombosis (CVT). CVT is more difficult to diagnose than arterial stroke; delay in hospital admission may postpone CVT treatment. The purposes of this study were: (1) to describe the delay between the onset of symptoms and hospital admission of patients with CVT, and (2) to identify the variables that influence that delay. We registered the interval (days) between the onset of symptoms and hospital admission in 91 consecutive patients admitted to 20 Portuguese hospitals between June 1995 and June 1998. We also studied the impact of admission delay on treatments (prescription of anticoagulants and the number of days elapsed between the onset of symptoms and start of anticoagulation and admission). Median admission delay was 4 days. Twenty-two (25%) patients were admitted within 24 h. Two thirds of the patients were admitted within 7 days and 75% within 13 days. In multiple logistic regression analysis, admission within 24 h was positively associated with mental status disorder (delirium or abulia; OR = 4.59; 95% CI = 1.41-14.89) and negatively associated with headache (OR = 0.03; 95% CI = 0.00-0.32). Presentation as isolated intracranial hypertension was associated with admission delay of more than 4 days (OR = 2.63; 95% CI = 0.97-7.14). Papilloedema was associated with an admission delay of more than 13 days (OR = 4.69; 95% CI = 1.61-13.61). There was no association between admission delay and the proportion of anticoagulated patients. The interval between onset of symptoms and start of anticoagulation was shorter in patients admitted earlier (p = 0.0001, for either admission within 24 h, 4 or 13 days). There is a considerable delay until the clinical picture associated with CVT is recognised as justifying hospital admission, especially when patients present with symptoms identical to isolated intracranial hypertension syndrome.

Seizures in cerebral vein and dural sinus thrombosis.

To describe early symptomatic and late seizures in a cohort of patients with acute cerebral vein and dural sinus thrombosis (CVDST) and to identify their determinants, we performed a prospective registry and follow-up study of CVDST patients admitted to 20 Portuguese hospitals, from June 1995 to June 1998. Of 91 registered patients, 31 (34%) had early symptomatic seizures; 29 (31.9%) as a presenting feature and 2 (2.1%) after admission. Early symptomatic seizures were more frequent in patients with motor and sensory deficits and in those with focal oedema/ischaemic infarcts or haemorrhages on admission CT/MR. On multivariate logistic regression analysis, sensory defects (OR = 7.8; 95% CI = 0.8-74.8) and a parenchymal lesion on admission CT/MR (OR = 3.7, 95% CI = 1.4-9.4) were found to be significant predictors of early symptomatic seizures. Seizures were directly related to acute death in 2 patients. Eight (9.5%) patients had late seizures, which were multiple in 4 (4.8%). Late seizures were more frequent in patients with early symptomatic seizures and with haemorrhage on admission CT/MR. Neither early symptomatic seizures nor late seizures were related to functional prognosis at the last follow-up (median = 1 year). There is a moderate risk of seizure recurrence early in the course and during the first year after CVDST. Seizures can be a cause of acute death, but might not have an independent influence on functional outcome. Pharmacological prevention of seizures after CVDST should probably be limited to patients with early symptomatic seizures and cerebral lesions on admission CT/MR.

Long-term prognosis of cerebral vein and dural sinus thrombosis. results of the VENOPORT study.

The purpose of this study was to analyze the long-term mortality, functional recovery and long-term complications of cerebral vein and dural sinus thrombosis (CVDST) admitted to Portuguese hospitals. A follow-up of symptomatic CVDST admitted to Portuguese hospitals since 1980 was performed. Fifty-one patients (retrospective cases) were re-evaluated during 1996; 91 consecutively admitted patients from 6/1995 to 6/1998 were followed up to 1999. In 1996, 4 (8%) of the retrospective cases had died (3 patients died in the acute phase), 4 (8%) could not be reached, 33 (64%) had recovered completely (Rankin 0 or 1) and 3 (6%) were dependent. The prospective cases had a mean follow-up of 1 year: 6 (7%) patients died in the acute phase, one (1%) died during follow-up, 75 (82%) recovered completely, and only 1 (1%) was dependent. For the prospective cases, worsening after admission (OR = 18.2; 95% CI = 2.9-112.4) and encephalopathy as the presenting syndrome (OR = 7.1; 95% CI = 1.2-40.9) predicted death or dependency, while absence of aphasia (OR 6.7, 95% CI = 1.6-33) and no worsening after admission (OR = 5.9; 95% CI = 1.6-20) predicted total recovery. During follow-up of the prospective cases, 4 (5%) patients had thrombotic events, 8 (10%) patients experienced seizures, 9 (11%) complained of severe headaches and 1 patient suffered severe visual loss. The long-term functional prognosis of patients with CVDST was fairly good with complete recovery in the majority of cases. However, these patients had a moderate risk of further thrombotic events and seizures.

Progressive multifocal leukoencephalopathy: unusual MRI findings and prolonged survival in a pregnant woman.

We report a biopsy-proven case of progressive multifocal leukoencephalopathy (PML) in a pregnant woman without obvious underlying immune disorder. MRI showed lesion enhancement and deep gray matter involvement, which are uncommon imaging patterns in PML. The clinical course in this case is also rather atypical, as the patient is alive 16 months after disease onset. The combination of these unusual characteristics in PML is unknown and indicates that the criteria for this disease may need to be redefined.

Diagnosis of stroke by the nonneurologist. A validation study.

BACKGROUND AND PURPOSE: The first medical contact of an acute stroke victim is often a nonneurologist. Validation of stroke diagnosis made by these medical doctors is poorly known. The present study seeks to validate the stroke diagnoses made by general practitioners (GPs) and hospital emergency service physicians (ESPs). METHODS: Validation through direct interview and examination by a neurologist was performed for diagnoses of stroke made by GPs in patients under their care and doctors working at the emergency departments of 3 hospitals. RESULTS: Validation of the GP diagnosis was confirmed in 44 cases (85%); 3 patients (6%) had transient ischemic attacks and 5 (9%) suffered from noncerebrovascular disorders. Validation of the ESP diagnosis was confirmed in 169 patients (91%); 16 (9%) had a noncerebrovascular diagnosis. Overall, the most frequent conditions misdiagnosed as stroke were neurological in nature (cerebral tumor, 3; subdural hematoma, 1; seizure, 1; benign paroxysmal postural vertigo, 1; peripheral facial palsy, 2; psychiatric condition, 6; and other medical disorders, 7). CONCLUSIONS: In the majority of cases, nonneurologists (either GPs or ESPs) can make a correct diagnosis of acute stroke. Treatment of acute stroke with drugs that do not cause serious side effects can be started before evaluation by a neurologist and CT scan.

Does timing and dosage of levodopa modify drug-induced dyskinesias and motor fluctuations? A retrospective analysis.

The aim of this study was to verify the influence of levodopa treatment in the development of long-term complications of Parkinson's disease (PD). We retrospectively analysed several epidemiological characteristics of the disease including long-term motor complications with timing and dose of levodopa in 50 patients. No differences between timing and initial dosage of levodopa were observed in patients who developed dyskinesias or motor fluctuations and those who did not. The patients who developed dyskinesias were younger and the rate of decline was faster in patients who developed motor fluctuations. These results suggest that late complications of levodopa are independent of the timing and initial dosage.

DYSBOT: a single-blind, randomized parallel study to determine whether any differences can be detected in the efficacy and tolerability of two formulations of botulinum toxin type A--Dysport and Botox--assuming a ratio of 4:1.

BACKGROUND: Elston and Russell discovered a difference in the biological potency of the English formulation of botulinum toxin type A or BTX-A (Dysport) and the American formulation (Botox). Potency of both is expressed in LD50 mouse units, but because of assay differences, these units are not equivalent. Since the first warning by Quinn and Hallet on the clinical importance of this issue, it has been impossible to reach a consensus on the conversion factor for the potency of these formulations. OBJECTIVE: To test the hypothesis that the conversion factor for the clinical potency of Dysport to Botox is approximately 4:1. DYSBOT is an acronym that results from adding "DYS" from Dysport with "BOT" from Botox. DESIGN: A single-blind, randomized, parallel comparison. A total of 91 patients with blepharospasm or hemifacial spasm were randomized to treatment with Dysport or Botox using a fixed potency ratio of 4:1. Clinical evaluations: The patients were evaluated at baseline (day of the treatment). 1 month after treatment, and whenever the effect was judged to be fading. Objective and functional rating scales were used as quantitative measures of the change in clinical status. Adverse reactions were collected using a systematic questionnaire. RESULTS: Using this ratio between products, both Dysport and Botox groups produced similar clinical efficacy and tolerability. For patients showing a positive response without the need of a booster, the duration of effect was 13.3 +/- 5.9 weeks for the Dysport group and 11.2 +/- 5.8 weeks for the Botox group. Of 48 patients, 11 (23%) needed booster treatment in the Dysport group compared with five (12%) of 43 in Botox group. Adverse events were noted in 24 (50%) of 48 patients in the Dysport group and 20 (47%) of 43 of the Botox-treated group. CONCLUSIONS: Using a 4:1 conversion ratio for Dysport and Botox, similar results were obtained for the two treatments in an appropriately powered study, suggesting that this conversion factor is a good estimate of their comparative clinical potencies.

The mitochondrial A3243G mutation presenting as severe cardiomyopathy.

A 6 year old Portuguese boy with dilated cardiomyopathy had abundant ragged red fibres in muscle (20% of total) and severe lactic acidosis. Molecular genetic analysis showed the A to G transition in the mitochondrial transfer RNALeu(UUR) gene at nt 3243 ("MELAS mutation"), which accounted for 88% and 68% of the total mtDNA in his muscle and blood, respectively. Molecular studies in blood from 16 maternal relatives identified lower percentages of the mutation only in the oligo-symptomatic mother and brother. This case reinforces the notion that cardiomyopathy can be the presenting and predominant clinical expression of the A3243G mutation.

Migraine and intracranial vascular malformations.

The relationships between migraine and A-V Malformations is a subject of controversy and the arguments are mainly based on case reports and retrospective data. To clarify this subject a structured inquiry and classification of headaches in large samples of patients with intracranial vascular malformations (IVM) is essential. The authors studied the prevalence of headaches in 51 patients with IVM admitted to our Department, between 1984 and 1992. The methods used were a review of medical records followed by a self-administered headache questionnaire and clinical interview using the IHS criteria for the diagnostic classification of headaches. The relative frequency of the different types of headaches was calculated and compared with the general population data. A correlative study of the headache characteristics with the type and location of the IVM was made. A high prevalence (47%) of migraine type headaches and a strong positive correlation (88.8%) between the site of AVM and side of the pain was found. This is highly suggestive but not conclusive of a pathophysiologic relationship between these entities. The conclusion drawn is that a prospective study of headaches by questionnaire or semi-structured clinical interview in patients with IVM is essential to discover the effective prevalence and characteristics of headaches associated with IVM and their relationships.