Carbon monoxide poisoning-induced nigrostriatal dopaminergic dysfunction detected using positron emission tomography (PET).

A malfunctioning heater caused a severe carbon monoxide (CO) intoxication leading to unconsciousness and predominantly right-sided extrapyramidal syndrome in a 29-year-old man. Follow-up included thorough clinical monitoring, and brain MRI and PET studies. Nine days after the poisoning, brain MRI showed symmetrical necrosis in the globus pallidi, but no abnormality was found in the substantia nigra. In addition, white matter periventricular lesions were seen. In a control scan 14 months later the white matter changes had subsided but small necrotic lesions were still noted bilaterally in the globus pallidi. A 6-[(18)F]fluoro-L-dopa PET examination performed 5 weeks after the intoxication revealed impaired presynaptic dopaminergic function in the left putamen whereas in the right putamen the dopaminergic activity was within normal limits. [(11)C] raclopride PET imaging 4 months after the poisoning showed no abnormality in postsynaptic D2 binding in the striatum. Clinically, the parkinsonian symptoms resolved 1.5 years after the poisoning. The final outcome of the recovery was excellent, and the patient returned to work. This is the first case reported where unilateral presynaptic, dopaminergic hypofunction in putamen could be confirmed with fluoro-l-dopa PET imaging on a patient with extrapyramidal syndrome caused by CO poisoning. Our results emphasize that CO intoxication can lead to striatal dopaminergic hypofunction, and that PET is a sensitive tool in evaluating extrapyramidal system after sudden neurotoxic insult.

Working capacity and cervical dystonia.

The objective of this questionnaire study was to assess the effect of cervical dystonia on patients' working capacity. Of the 303 working-aged members of the Finnish Dystonia Association (N = 433) who participated in the study 247 (82%) had cervical dystonia. Their median age was 50 years, the median duration of CD symptoms was 12.3 years. Most (78%) subjects were on botulinum toxin treatment. Ninety-seven (39%) had retired because of CD at a median age of 48 years; 96 (39%) of the subjects were working: 87 full-time and 9 part-time. The remaining participants were on sick leave, unemployed, studying or retired of other reasons. Retirement occurred more than ten years earlier compared with the general Finnish population. All possibilities to help CD patients to continue longer in work should be considered early.

Neurological symptoms and natural course of xeroderma pigmentosum.

We have prospectively followed 16 Finnish xeroderma pigmentosum (XP) patients for up to 23 years. Seven patients were assigned by complementation analysis to the group XP-A, two patients to the XP-C group and one patient to the XP-G group. Six of the seven XP-A patients had the identical mutation (Arg228Ter) and the seventh patient had a different mutation (G283A). Further patients were assigned to complementation groups on the basis of their consanguinity to an XP patient with a known complementation group. The first sign of the disease in all the cases was severe sunburn with minimal sun exposure in early infancy. However, at the time the diagnosis was made in only two cases. The XP-A patients developed neurological and cognitive dysfunction in childhood. The neurological disease advanced in an orderly fashion through its successive stages, finally affecting the whole nervous system and leading to death before the age of 40 years. Dermatological and ocular damage of the XP-A patients tended to be limited. The two XP-C patients were neurologically and cognitively intact despite mild brain atrophy as seen by neuroimaging. The XP-G patients had sensorineural hearing loss, laryngeal dystonia and peripheral neuropathy. The XP-C patients had severe skin and ocular malignancies that first presented at pre-school age. They also showed immunosuppression in cell-mediated immunity. Neurological disease appears to be associated with the complementation group and the failure of fibroblasts to recover RNA synthesis following UV irradiation, but not necessarily to the severity of the dermatological symptoms, the hypersensitivity of fibroblasts to UVB killing or the susceptibility of keratinocytes to UVB-induced apoptosis.

Methanol intoxication-induced nigrostriatal dysfunction detected using 6-[18F]fluoro-L-dopa PET.

Ingestion of windshield washer liquid resulted with an acute severe methanol intoxication in a 49-year old man. He developed optic atrophy with blindness, and an extrapyramidal syndrome. Putaminal injury and hyperintensity in the subcortical white matter was seen in a brain MRI. PET scanning with 6-[18F]fluoro-L-dopa confirmed symmetrical impaired presynaptic dopaminergic activity in the striatum, indicative of functional impairment of dopaminergic nigrostriatal neurons. The striatal uptake was more markedly impaired in the putamina (40% of controls) than in the caudate nuclei (60% of controls). To our knowledge, this is the first report of an 18F-dopa PET scanning result in a case of an acute methanol poisoning.

Geographical variation of medicated parkinsonism in Finland during 1995 to 2000.

We performed a nation-wide study on geographical variation in the incidence and prevalence of medicated parkinsonism among the Finns aged > or =30 years using Bayesian spatial conditional autoregressive models. Registry of reimbursed medication for parkinsonism and a prescription database of purchase of these drugs were used to identify the study subjects. They were located by the map coordinates of the place of residence and aggregated into regular 100 km(2) grid cells. A total of 7,190 incident and 10,616 prevalent cases were found. The age-adjusted annual incidence was 32.6/100,000 (95% HDR 31.8-33.4) during the years 1995 to 2000 and prevalence was 268/100,000 (95% HDR 263-274) in 2000. The male to female ratio was 1.45 (95% HDR 1.39-1.51) in incidence and 1.54 (95% HDR 1.47-1.61) in prevalence. There was strong evidence for geographic variation in incidence and prevalence. A zone with high incidence and prevalence was identified in the eastern and central part of Finland. There was no evidence for difference in incidence and prevalence between urban and rural areas. The marked (more than two-fold) geographic variation can hardly be caused solely by practices of the registration and collection of data on diagnosis or by methodological issues, but rather suggests to geographic variation in protective and predisposing factors of Parkinsonism in Finland.

Transoesophageal echocardiography should be considered in patients with ischaemic stroke or transient ischaemic attack.

BACKGROUND AND PURPOSE: In this present study, we tried to find out if there is a subgroup of patients that should not undergo transoesophageal echocardiography (TEE) after an ischaemic stroke or transient ischaemic attack (TIA). METHODS: A total of 441 consecutive unselected patients with ischaemic stroke or TIA suitable for anticoagulation were examined with TEE in the acute phase. The patients were divided into five subcategories according to their rhythm, age and the findings in carotid sonography, and into two groups according to the presence of clinical risk factors for ischaemic stroke or TIA. RESULTS: From the 441 studied patients, 60 (14%) had chronic or paroxysmal atrial fibrillation (AF) and 381 (86%) were in sinus rhythm (SR). Of the patients in SR, 46 (12%) were below 50 years old. The carotid sonography was conducted in 240 patients above 50 years old and in SR, and <50% internal carotid artery (ICA) stenosis was found in 194 (81%) patients and > or =50% ICA in 46 (19%) patients. Potential cardiac sources of embolism were found in patients both with AF or in SR (70% versus 46%), both below and above 50-year-old patients in SR (37% versus 47%), both in over 50-year-old patients in SR with <50% ICA stenosis and > or =50% ICA stenosis (41% versus 61%) and in patients in SR either without or with clinical risk factors for ischaemic stroke or TIA (43% versus 51%). On the basis of the TEE study, oral anticoagulation was started in 36 (9%) patients in SR. CONCLUSION: These results support TEE in patients with ischaemic stroke or TIA who are candidates for receiving oral anticoagulation.

Substantial thalamostriatal dopaminergic defect in Unverricht-Lundborg disease.

PURPOSE: Unverricht-Lundborg disease (ULD) is currently classified as progressive myoclonus epilepsy. Myoclonus, the characteristic symptom in ULD, suggests that dopamine neurotransmission may be involved in the pathophysiology of ULD. Our purpose was to examine brain dopaminergic function in ULD patients. METHODS: Four genetically and clinically diagnosed ULD patients and eight healthy controls were scanned with [(11)C]raclopride-PET. PET images were coregistered to individual 1.5 T MR images and region-of-interest analysis was performed for the striatum and thalamus. Standardized uptake values and individual voxel-wise binding potential maps of the patients and controls were also analyzed. RESULTS: ULD patients had markedly higher (31-54%) dopamine D2-like receptor availabilities than healthy controls in both the striatum and the thalamus. The proportionally highest binding potentials were detected in the thalamus. There were no significant differences in the cerebellar uptake of [(11)C]raclopride in ULD patients versus healthy controls. Voxel-based results were in accordance with the region-of-interest analysis. CONCLUSIONS: These results suggest that dopaminergic modulation at the level of the striatum and thalamus could be a crucial factor contributing to the symptoms of ULD. In the light of our data, we propose that ULD with dopamine dysfunction and dyskinetic symptoms shares certain pathophysiological mechanisms with classical movement disorders. Future studies are therefore warranted to study the effect of dopaminergic pharmacotherapy in ULD.

Parkinson's disease and working capacity.

The purpose of the present study was to establish how Parkinson's disease (PD) affects working capacity. Altogether, 937 (70%) of 1,343 working-aged members of the Finnish Parkinson Association participated in a questionnaire study. The ages of the subjects were between 29 and 65 years, median 59.0 years; 508 (54%) were men. The median (quartile range) duration of PD symptoms was 7.3 (4.3-11.3) years, and the median self-estimated severity of the disease on the Hoehn & Yahr scale was 2. Only 150 of 937 subjects (16%) were still working: 112 (12%) full-time and 38 (4%) part-time. Among those 343 (37%) who had retired purely because of PD at a median age of 53.4 years, the median working time was 1.7 years after established diagnosis. In part-time work, PD patients had been able to continue for a median of 4.3 years. PD often leads to early retirement; compared with the general Finnish population of similar age, PD patients had retired on the average 6 years earlier. Young age, mild symptoms, and short duration of the disease as well as adjustments enabling easier employment were associated with the possibility to continue longer in the work force.

Carotid sonography and transesophageal echocardiography in patients with ischemic stroke or transient ischemic attack in the territory of the carotid artery.

PURPOSE: To assess the benefit of combining carotid sonography and transesophageal echocardiography (TEE) for the evaluation of patients with stroke or transient ischemic attack (TIA) in the territory of the carotid artery. METHODS: During a 2-year period in Turku University Hospital, consecutive in patients with stroke or TIA who were candidates for carotid endarterectomy and for oral anticoagulation were evaluated with carotid sonography for symptomatic moderate (50-69%) or severe (>or=70%) internal carotid artery (ICA) stenosis, and with TEE for potential cardiac sources of embolism. RESULTS: In 20% (40/197) of patients, a severe symptomatic ICA stenosis and/or a major risk factor for a cardiac source of embolism were found. In 56% (110/197) of patients, a moderate or severe symptomatic ICA stenosis and/or a potential cardiac source of embolism were found, whereas 11% (21/197) of patients had both a moderate or severe symptomatic ICA stenosis and a potential cardiac source of embolism. CONCLUSIONS: This study suggests that the presence of a moderate or severe symptomatic ICA stenosis does not exclude the presence of a potential cardiac source of embolism and vice versa. Carotid sonography and TEE complement each other and are valuable diagnostic tools that should be recommended in patients with ischemic stroke or TIA in the territory of the carotid artery when they are candidates for carotid endarterectomy and for oral anticoagulation.

Successful pregnancy of a patient with Balo's concentric sclerosis.

Balo's concentric sclerosis is a severe demyelinating disease with poor prognosis. To date, nothing is known about the effects of pregnancy on the course of Balo's disease. We describe here the first successful pregnancy of a patient with Balo's concentric sclerosis. Upon neurological worsenings during pregnancy, our patient was treated with high-dose methylprednisolone and plasma-exchange. Intravenous immunoglobulin and interferon-beta-1a were given postpartum. At the last follow-up visit 2.5 years after the delivery the patient had only minor residual symptoms.

Diagnosis of enteroviral meningitis by use of polymerase chain reaction of cerebrospinal fluid, stool, and serum specimens.

BACKGROUND: Because enteroviruses can be detected in various clinical samples during enteroviral meningitis, we analyzed the combined diagnostic utility of polymerase chain reaction (PCR) of cerebrospinal fluid (CSF), feces, and serum for detection of enterovirus in specimens obtained from adults with aseptic meningitis or encephalitis. METHODS: PCR results were analyzed for 34 adults for whom enteroviral meningitis was diagnosed on the basis of virus isolation and antibody detection in our hospital during 1999-2003. PCR results were also analyzed for 77 adults with meningitis or encephalitis of another defined cause for whom this assay was used for diagnostic evaluation during that period. RESULTS: Twenty-six (76%) of 34 CSF samples and 24 (96%) of 25 fecal samples collected from patients with enteroviral meningitis had positive PCR results. The diagnostic yield of the test was lower for CSF specimens obtained >2 days after clinical onset, compared with CSF collected < or =2 days after onset. Instead, PCR of feces was highly useful also later, because 12 of the 13 fecal specimens obtained 5-16 days after clinical onset had positive test results. None of 75 CSF samples and 2 of 48 fecal samples obtained from patients with nonenteroviral infection had positive PCR results. All serum samples were PCR negative. CONCLUSIONS: PCR of fecal specimens obtained throughout the course of enteroviral meningitis had the highest clinical sensitivity for detecting enterovirus. It is recommended that, in addition to performance of CSF PCR, fecal samples collected from patients with suspected enteroviral meningitis should be tested by PCR, especially when the duration of symptoms is >2 days.

Recurrent lymphocytic meningitis: the role of herpesviruses.

BACKGROUND: Herpes simplex virus 2 (HSV-2) and HSV-1 have been recognized as causes of recurrent aseptic lymphocytic meningitis (RALM). However, the role of other herpesviruses has not been systematically assessed. OBJECTIVES: To evaluate the cause of RALM by using polymerase chain reaction (PCR) tests detecting varicella-zoster virus (VZV), cytomegalovirus (CMV), or human herpesvirus 6 (HHV-6), in addition to HSV, on cerebrospinal fluid (CSF) samples; and to assess the utility of PCR and antibody analyses in consecutive episodes of RALM. DESIGN: The PCR and antibody results for herpesviruses were analyzed from 14 patients having 48 episodes of RALM. RESULTS: The CSF PCR results for VZV, CMV, and HHV-6 were negative in 12, 10, and 11 patients investigated, respectively, and antibodies against VZV, CMV, and HHV-6 showed only old immunity. Herpes simplex virus 2 was detected from the CSF in 10 patients, and HSV-1 in 1 patient. In 6 of these 11 patients, the HSV PCR result was positive in more than one disease episode. A significant increase of serum antibodies for HSV was seen in only 1 of 15 episodes examined. An intrathecal antibody response to HSV was not recognized in 9 episodes investigated in these 11 patients. CONCLUSIONS: We could not find evidence of VZV, CMV, or HHV-6 in the pathogenesis of RALM, although most patients were previously infected by those viruses. Herpes simplex virus 2 was detected from the CSF in most patients, and often repeatedly, which further confirms the role of this virus in RALM. The causative diagnosis was obtained only by PCR, whereas antibody analysis was not clinically useful.

The risk of stroke following coronary revascularization -- a population-based long-term follow-up study.

OBJECTIVE: To study the incidence and risk factors of stroke after coronary artery bypass grafting (CABG) or percutaneous transluminal coronary angioplasty (PTCA). DESIGN: During 1983-1992, coronary revascularization procedures (n = 2160) were recorded in patients aged 35-64 years as part of the population-based FINMONICA Myocardial Infarction Register. The FINMONICA Stroke Register and National Hospital Discharge Register were used to ascertain subsequent stroke events in such patients. RESULTS: During the average follow-up of 5.83 years, 155 patients (7.2%) had a stroke. The cumulative incidence of stroke was 1.55% in the first year after revascularization and varied between 0.8 and 1.4% during subsequent years. In Cox proportional hazard models the relative risk of stroke was 3.01 (p = 0.0007) for a previous stroke, 2.61 (p = 0.0001) for diabetes mellitus, 2.15 (p = 0.007) for low income (compared with high income), 2.06 (p = 0.03) for male sex, and 1.43 (p = 0.02) for a 10-year increment in age. CONCLUSION: The incidence of stroke during the first year after revascularization was five times higher than among the age- and sex-matched general population. Patients with a previous stroke, diabetes mellitus, advanced age, male sex and low socioeconomic status need special attention because of increased risk of stroke after CABG or PTCA.

Probabilistic sensitivity analysis for evaluating cost-utility of entacapone for Parkinson's disease.

The objective was to assess uncertainty in a cost-utility analysis of adjunct entacapone treatment with levodopa among Parkinson's disease patients by probabilistic sensitivity analysis using second-order simulation methods. The cost-effectiveness of two treatment alternatives of Parkinson's disease - levodopa with or without entacapone - was compared in a cost-utility analysis employing a Markov model. Monte Carlo simulation was used to quantify the uncertainty due to sampling variation. The results strengthened confidence in the conclusions that entacapone as an adjunctive treatment to levodopa is both cost-saving and increases the quality of life of Parkinson's disease patients.