Etiology of aseptic meningitis and encephalitis in an adult population.

OBJECTIVE: To investigate the etiology of aseptic meningitis and encephalitis in an adult population using modern microbiologic methods. METHODS: Consecutive patients (ages > or =16) with aseptic meningitis or encephalitis treated in Turku University Hospital, Finland, during 1999 to 2003 were included in the study. Microbiologic tests were performed, including CSF PCR tests for enteroviruses, herpes simplex virus (HSV) 1, HSV-2, and varicella zoster virus (VZV), as well as serum and CSF antibody analysis for these viruses. Antibody testing was also performed for other pathogens commonly involved in neurologic infections. Virus culture was performed on CSF, fecal, and throat swab specimens. RESULTS: Etiology was defined in 95 of 144 (66%) patients with aseptic meningitis. Enteroviruses were the major causative agents (26%), followed by HSV-2 (17% of all, 25% of females) and VZV (8%). Etiology was identified in 15 of 42 (36%) patients with encephalitis, VZV (12%), HSV-1 (9%), and tick-borne encephalitis virus (9%) being the most commonly involved pathogens. Etiologic diagnosis was achieved by PCR in 43% of the patients with meningitis and in 17% of those with encephalitis. CONCLUSIONS: Enteroviruses and HSV-2 are the leading causes of adult aseptic meningitis, and PCR is of diagnostic value. However, in most cases of encephalitis, the etiology remains undefined.

Aetiological diagnosis of brain abscesses and spinal infections: application of broad range bacterial polymerase chain reaction analysis.

OBJECTIVE: To evaluate the usefulness of the broad range bacterial rDNA polymerase chain reaction (PCR) method combined with DNA sequencing in the aetiological diagnosis of intracranial or spinal infections in neurosurgical patients. METHODS: In addition to conventional methods, the broad range bacterial PCR approach was applied to examine pus or tissue specimens from cerebral or spinal lesions in patients treated in a neurosurgical unit for a clinical or neuroradiological suspicion of bacterial brain abscess or spondylitis. RESULTS: Among the 44 patients with intracranial or spinal lesions, the final diagnosis suggested bacterial disease in 25 patients, among whom the aetiological agent was identified in 17. A causative bacterial species was identified only by the rDNA PCR method in six cases, by both the PCR methodology and bacterial culture in six cases, and by bacterial culture alone in five. All samples in which a bacterial aetiology was identified only by the PCR approach were taken during antimicrobial treatment, and in three patients the method yielded the diagnosis even after >/= 12 days of parenteral treatment. One case also identified by the PCR approach alone involved a brain abscess caused by Mycoplasma hominis, which is not readily cultured by routine methods. CONCLUSIONS: In patients with brain abscesses and spinal infections, the broad range bacterial rDNA PCR approach may be the only method to provide an aetiological diagnosis when the patient is receiving antimicrobial treatment, or when the causative agent is fastidious.

Transoesophageal echocardiography in selecting patients for anticoagulation after ischaemic stroke or transient ischaemic attack.

OBJECTIVES: To investigate prospectively the role of transoesophageal echocardiography (TEE) in selecting patients for anticoagulation in an unselected stroke population. METHODS: Transthoracic echocardiography (TTE) and TEE were done in all clinically suitable hospitalised patients (n = 457) with transient ischaemic attack or ischaemic stroke in the acute phase during a two year period in Turku University Hospital. 441 patients were successfully evaluated for cardiac sources of embolism using TEE within 31 days of the event. RESULTS: A major risk factor for a cardiac source of embolism excluding atrial fibrillation, acute myocardial infarction, and prosthetic valve was detected in 10% of patients and a minor risk factor for a cardiac source of embolism in 46%. When a major risk factor of a cardiac source of embolism was detected using TTE or TEE and no contraindications were present, the patient was given anticoagulation drugs. If a minor risk factor for a cardiac source of embolism was detected, anticoagulation treatment was started after clinical assessment, if no contraindications were present. In 62 (14%) cases, the patient was given oral anticoagulation drugs or the necessity of ongoing anticoagulation treatment was confirmed on the basis of TEE. When these anticoagulation treated patients were evaluated using logistic regression analysis, they were found to have significantly more atrial fibrillation and histories of myocardial infarctions. Moreover, the patients were mainly men. When patients in sinus rhythm and without any history of cardiac disease were analysed, 8% of patients were found to have been given anticoagulation drugs on the basis of TEE data. CONCLUSION: This study suggests that TEE should be used in patients with stroke even without any clinical evidence of cardiac disease when the patients are candidates for anticoagulation.

Botulinum toxin in the treatment of cricopharyngeal dysphagia.

Dysphagia is a common symptom in various neurological disorders affecting pharyngeal functions. Cricopharyngeal dysfunction is one of the major findings in these patients. The most effective treatment for restoring normal swallowing function in persistent cricopharyngeal dysfunction is cricopharyngeal myotomy, especially when mechanical obstruction or a well-localized neuromuscular dysfunction, such as a cricopharyngeal muscle spasm, is present. However, when there is a more diffuse neurological disorder present the results of surgery are more disappointing. In unclear cases, or in patients with temporary problems, no good method other than swallowing training, bougienage, and tube feeding are available. During the past decade, botulinum toxin has been found to be of therapeutic value in the treatment of a variety of neurological disorders associated with inappropriate muscular contractions such as torticollis and spasmodic dysphonia. Recently, injections of botulinum toxin in patients with cricopharyngeal muscle dysfunction have been reported to result in marked relief of dysphagia. In this article we describe our experiences with botulinum toxin injections to treat four patients suffering from deglutition problems and cricopharyngeal dysphagia of different origins. Botulinum toxin was injected into the cricopharyngeus muscle that was identified by endoscopy under general anesthesia. In this study, no major side effects were observed. Three patients obtained a significant improvement of esophageal symptoms after the first injection. The treatment had limited effect in one patient who had reflux disease and only slight cricopharyngeus dysfunction.

Familial occurrence of Parkinson's disease in a community-based case-control study.

Purpose: To study the occurrence of Parkinson's disease (PD) in the relatives of parkinsonian patients (n=119), and of their matched controls (n=238).Scope: More patients reported a positive family history of PD in their first degree relatives, compared to their controls (OR 2.7, 95% CI 1.3-5.9), and the incidence of PD among those relatives was also significantly higher (OR 1.4, 95% CI 1.1-1.8).Conclusions: Familial occurrence of PD is not necessarily a sign of genetic mechanisms in the etiology of PD. Shared environment with common risk factors might be even more important.

Ultraviolet-B-induced apoptosis and cytokine release in xeroderma pigmentosum keratinocytes.

We have assessed the ability of xeroderma pigmentosum and normal keratinocytes grown out from skin biopsies to undergo apoptosis after irradiation with ultraviolet B. Keratinocytes have been studied from xeroderma pigmentosum complementation groups A (three biopsies), C (three biopsies), D (one biopsy), xeroderma pigmentosum variant (two biopsies), and Cockayne syndrome (one biopsy). The three xeroderma pigmentosum group A and the xeroderma pigmentosum group D samples were at least six times more sensitive than normal cells to ultraviolet B-induced apoptosis. The xeroderma pigmentosum variant samples showed intermediate susceptibility. Xeroderma pigmentosum group C samples proved heterogeneous: one showed high sensitivity to apoptosis, whereas two showed near normal susceptibility. The Cockayne syndrome sample showed the high susceptibility of xeroderma pigmentosum groups A and D only at a higher fluence. These results suggest that the relationships between repair deficiency, apoptosis, and susceptibility to skin cancer are not straightforward. Ultraviolet B-induced skin cancer is also thought to be due in part to ultraviolet B-induced impairment of immune responses. The release of the inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha from cultured xeroderma pigmentosum keratinocytes tended to occur at lower fluences than in normals, but was less extensive, and was more readily inhibited at higher fluences of ultraviolet B.

The quality of life in Parkinson's disease.

The objective of this study was to examine the quality of life in patients with Parkinson's disease (PD) in a community-based sample (n = 228 patients) using a Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) as a measure. Associations to the variables age, age at onset, duration, clinical stage (Hoehn and Yahr), depression (Zung), and dementia (MMSE) were studied. Women scored significantly lower on five of the eight dimensions of SF-36. Depression, as measured in this study, was more common among parkinsonian women than men. Depression was the factor that was associated most significantly with the experienced quality of life, according to SF-36. With physical functioning, only the clinical stage had a more significant association than depression. To improve the quality of life in patients with PD, it is necessary to make every effort to recognize and relieve the depression of patients with PD.

Environmental risk factors in Parkinson's disease.

We studied the environmental risk factors of Parkinson's disease (PD) in Finland, particularly those related to rural environment, in a prevalence material in 1992. The population numbered 196,864 people, including urban and rural areas. In this community-based study, we used a case-control method with personal investigation of the case subjects (n = 123) and matched control subjects (n = 246). Analyses were carried out by conditional logistic regression model. Case subjects had far fewer domestic animals at home during their lifetime, including cows, sheep, pigs, and chickens. The difference was even more obvious in those under the age of 20 years, including also cats and horses, but diminished after 20 years. The number of different animal species was smaller with case subjects as was the duration of animal contacts. Case subjects found their work physically heavier and exercised more. The mean age at onset in ever-smoking men was significantly higher than in never-smoking men. No special reason for non-smoking increased, and a physical reason decreased the risk of PD. Area of birth or living, farming and other occupations, types of drinking water, pesticide and herbicide use, head injuries, use of alcohol, education, and carbon monoxide poisonings were similar among case subjects and control subjects. In conclusion, domestic animals, or something that is connected with the animals, may have a protecting effect against PD. Alternatively, the observed negative associations of domestic animals at home and subsequent PD may only be a marker of other environmental conditions or lifestyles.

Changing epidemiology of Parkinson's disease in southwestern Finland.

OBJECTIVE: Investigation of the epidemiology of PD in southwestern Finland in 1992 (population 196,864), including urban and rural areas, with a comparison with a similar study, done in the same area in 1971, to evaluate the temporal pattern. METHODS: Community-based method of patient ascertainment with personal investigation of cases. RESULTS: The age-adjusted prevalence (to the Finnish general population in 1991) was 139 per 100,000 population in 1971 and 166 in 1992. Prevalence ratio for PD in men versus women was 1.2 (NS) in 1971 and 1.7 in 1992 (p < 0.001); in the rural versus urban populations the prevalence ratio was 0.8 (NS) in 1971 and 1.3 in 1992 (p = 0.013). The age-specific prevalence rates showed a male preponderance in all age groups in 1992 and a rural preponderance in the age groups over 60 years. In 1992, compared with 1971, the male and rural preponderance occurred in the age groups over 70 years. The age-adjusted incidence was 15.7 per 100,000 population in 1971 and 14.9 in 1992. Relative risk for PD in men versus women was 0.9 (NS) in 1971 and 1.9 (p < 0.001) in 1992, and in rural versus urban populations 1.4 (p = 0.093) in 1992. CONCLUSIONS: A very significant male and a significant rural predominance, not seen in 1971, suggests a possible environmental causative factor, perhaps more frequent in the rural environment, associated with PD. Men may be either more exposed to it or more susceptible to its effects than women.

Intracranial aneurysms in three patients with disseminated Lyme borreliosis: cause or chance association?

METHODS: Three patients with Borrelia burgdorferi infection and intracranial aneurysms are described. RESULTS: All three patients had neurological symptoms. Perivascular and vasculitic lymphocytic inflammation were detected in the brain biopsy specimen of one patient. The aneurysm was located in the internal carotid arteries in two patients and in the basilar artery in one patient. The aneurysm ruptured in two patients. CONCLUSIONS: Cerebral lymphocytic vasculitis and intracranial aneurysms may be associated with B burgdorferi infection. It is suggested that inflammatory changes caused by B burgdorferi in vessel walls may be a pathogenetic mechanism for the formation of aneurysms.

A double blind, randomised, parallel group study to investigate the dose equivalence of Dysport and Botox in the treatment of cervical dystonia.

OBJECTIVE: This study was designed to establish whether a ratio of three units of Dysport is equivalent to one unit of Botox for the treatment of cervical dystonia. METHODS: Patients with predominantly rotational cervical dystonia, and a minimum of four previous Botox treatments, were randomised to receive either the clinically indicated dose of Botox or three times that dose in Dysport units. Study botulinum toxin was administered in a double blind fashion, to one or more clinically indicated muscles, at one or more sites per muscle. Patients returned for assessment two, four, eight, and 12 weeks after treatment. RESULTS: A total of 73 patients (Dysport, 38; Botox, 35) were entered. The Dysport group received a mean (SD) dose of 477 (131) (range 240-720) Dysport units, and the Botox group received a mean (SD) dose of 152 (45) (range 70-240) Botox units. The mean (SEM) post-treatment Tsui scores for the Dysport group (4.8 (0.3)) and the Botox group (5.0 (0.3)) were not statistically different (p=0.66). The study had 91% power to detect a clinically significant difference of two points. Both groups showed substantial improvement in Tsui score by week 2 (mean (SD); Dysport, 46 (28)%; Botox, 37 (28)%), with a peak effect at week 4 (mean (SD); Dysport, 49 (29)%; Botox, 44 (28)%). A similar response profile was seen for other assessments of efficacy. The duration of effect, assessed by time to retreatment, was also similar (mean (SD); Dysport, 83.9 (13.6) days; Botox, 80.7 (14.4) days; p=0.85). During the study 22 of 38 (58%) Dysport patients reported 39 adverse events, and 24 of 35 (69%) Botox patients reported 56 adverse events (p=0.35). A global assessment of efficacy and safety considered that 29 of 38 (76%) Dysport patients and 23 of 35 (66%) Botox patients were treatment successes (p=0.32). CONCLUSION: Patients with predominantly rotational cervical dystonia treated with the clinically indicated dose of Botox or three times that dose in Dysport units show similar improvements and do not have significantly different safety profiles.

Atrial fibrillation in older stroke patients: association with recurrence and mortality after first ischemic stroke.

OBJECTIVES: The objective of this study was to determine the association of atrial fibrillation (AF) with stroke recurrence and mortality and with the causes of death in ischemic stroke patients aged 75 years and older. DESIGN: A population-based study. SETTING: The cities of Turku and Kuopio in Finland. PARTICIPANTS: The study cohort consisted of 2635 consecutive patients aged 75 years and older, with a first ischemic stroke, registered in the FINMONICA Stroke Register. MEASUREMENTS: 28-day and 1-year stroke mortality, causes of death, and recurrence of stroke. RESULTS: There were 767 stroke patients with AF (mean age 82.2) and 1868 patients without AF (mean age 81.4). Mortality was higher in the AF group both 28 days (33.9% vs 28.1%, P = .003) and 1 year after the attack (52.7% vs 43.0%, P < .001). The age- and sex-adjusted relative risk of death at 28 days was 1.25 in the AF group (95% confidence interval (CI) 1.04-1.50, P = .018), and at 1 year it was 1.41 (95% CI 1.18-1.67, P < .001). In a Cox proportional hazards model, 1-year mortality risk comparing the AF-group with non-AF group was 1.24 (95% CI 1.10-1.39, P < .001). The strongest risk factor predicting 1-year mortality was recent myocardial infarction (MI) (RR 1.90, 95% CI 1.49-2.42). Myocardial infarction was more often the underlying cause of death in the AF group during the period of 28 days, but not from 28 days up to 1 year. The 1-year recurrence rate among those alive at day 28 was 11.5% in the AF group and 9.4% in the non-AF group (P = .240). CONCLUSION: Recent MI and AF are independent negative prognostic factors in older patients with stroke. Although the relative risk estimates attributable to AF are of the same magnitude in older as in middle-aged stroke patients, the much higher prevalence of AF in the older patients emphasizes its absolute impact on the mortality and recurrence after the first ischemic stroke in the age group 75 years and older. The treatment of coexisting cardiac disease also has the potential to prevent deaths and recurrent stroke events in older persons.

Paraparesis caused by a bilateral cervical synovial cyst.

We describe a 64-year-old man who suffered from rapidly progressive paraparesis. At operation the cervical cord of the patient was found to be displaced anteriorly due to compression caused by an epidural synovial cyst. The cyst was located bilaterally on the dorsolateral aspect of both CVII facet joints. The rapid development of paraparesis in this patient can, thus, be explained by the enlargement of the cyst on both sides of the spinal cord. After microsurgical removal of the cystic tumor, the recovery of the patient was good. Cervical epidural cysts are extremely rare, and only anecdotal cases have been reported in the literature. Among all previously described patients the present case is unique due to the bilateral location of the cyst.

Atrial fibrillation and stroke. Mortality and causes of death after the first acute ischemic stroke.

BACKGROUND AND PURPOSE: Atrial fibrillation (AF) is a risk factor for stroke. This study was undertaken to determine the influence of AF on the mortality of stroke patients and on the causes of death after a stroke event. METHODS: Patients with first ischemic stroke who were .35 to 74 years old and registered in the FINMONICA stroke register during 1982 through 1992 were analyzed (n = 6912). There were 642 patients with AF (9.3%) (mean age, 67 years) and 6270 patients without AF (90.3%) (mean age, 63 years). The association between AF and stroke mortality was investigated by use of logistic regression and Cox proportional hazards models. RESULTS: Mortality was higher in the AF group both at 28 days (19.5% versus 14.4%, P < .001) and 1 year after the attack (30.5% versus 21.8%, P < .001). After adjustment for age and sex, the odds ratio for 28-day case fatality (AF versus non-AF) was 1.27 (95% CI, 1.03 to 1.56; P = .003), and that for 1-year mortality was 1.36 (95% CI, 1.14 to 1.63; P < .001). In the proportional hazards model, AF was a significant independent risk factor for 1-year mortality (hazard ratio, 1.26; 95% CI, 1.09 to 1.46; P = .002). Cardiac causes of death were more common in the AF group at the acute stage. In the course of 1 year, there were no differences in the distributions of causes of death. CONCLUSIONS: Stroke patients with AF are at high risk of death both at the acute phase of stroke and during the subsequent year after the first acute stroke event. Mortality from cardiac diseases prevailed in the AF group during the acute phase of stroke. Careful cardiac evaluation and treatment are essential in patients with AF and stroke.

Inflammatory brain changes in Lyme borreliosis. A report on three patients and review of literature.

Despite a rapid increase in the number of patients with Lyme neuroborreliosis (LNB), its neuropathological aspects are poorly understood. The objective of this study was evaluation of neuropathological, microbiological, and magnetic resonance imaging (MRI) findings in three patients with the Borrelia burgdorferi infection and neurological disease from whom brain tissue specimens were available. Perivascular or vasculitic lymphocytic inflammation was detected in all specimens. Large areas of demyelination in periventricular white matter were detected histologically and by MRI in one patient. The disease had a fatal outcome in this patient. Brain MRI suggested malignancies in two patients before histopathological studies were carried out. One of these two patients was a child with sudden hemiparesis. Another was a 40-year-old man presenting with epileptic seizures and MRI-detected multifocal lesions, which disappeared after repeated courses of antibiotics. We conclude that cerebral lymphocytic vasculitis and multifocal encephalitis may be associated with B. burgdorferi infection. The presence of B. burgdorferi DNA in tissue samples from areas with inflammatory changes indicates that direct invasion of B. burgdorferi may be the pathogenetic mechanism for focal encephalitis in LNB.