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Biomedical subjects

J Launes

Publications and source records attributed to J Launes.

At least 19 recordsLinked to original sources

How useful is [123I]beta-CIT SPECT in clinical practice?

OBJECTIVE: To assess the accuracy and clinical usefulness of [(123)I]beta-CIT (2beta-carbomethoxy-3beta-(4-iodophenyl)tropane) SPECT in the differential diagnosis of Parkinson's disease. SUBJECTS: 185 consecutive patients with symptoms of movement disorder were studied. The diagnoses were Parkinson's disease (92), essential tremor (16), vascular parkinsonism (15), various Parkinson plus syndromes (P+) (12), dementia with Lewy bodies (DLB) (5), dystonia (5), drug induced movement disorder (12), and other diagnoses (8). A reference group (psychogenic parkinsonism) comprised 20 subjects with complaints suggesting extrapyramidal disease but with no unequivocal signs on clinical examination and no abnormalities on brain imaging. RESULTS: beta-CIT uptake was significantly lower in the whole striatum as well as separately in the putamen and in the caudate nucleus in Parkinson's disease than in the reference group or in drug induced movement disorder, essential tremor, or dystonia. The uptake of beta-CIT in the vascular parkinsonism group was heterogeneous and mean beta-CIT uptake fell between the reference group and the Parkinson's disease group. In the P+ and DLB groups the striatal uptake ratios overlapped those of the Parkinson's disease group. CONCLUSIONS: [(123)I]beta-CIT SPECT may not be as useful a tool in the clinical differential diagnosis of Parkinson's disease as was previously believed, but it was 100% sensitive and specific for the diagnosis in younger patients (age <55 years). In older patients (age >55 years) specificity was substantially lower (68.5%). This differential specificity reflected the different distribution of differential diagnostic disorders (P+, DLB, vascular parkinsonism) in the older and younger age groups.

Age Factors↗

Assessment of a DJ-1 (PARK7) polymorphism in Finnish PD.

Mutations in DJ-1 are a cause of autosomal recessive parkinsonism. Polymorphism of genes implicated in hereditary forms of parkinsonism may be a predisposing factor in sporadic Parkinson's disease (PD). The authors analyzed whether a polymorphism (g.168_185del) within exon 1 of DJ-1 contributes to the risk of sporadic PD in a Finnish case-control series. This gene does not play a major role in the genetic predisposition to PD in this population.

Adult↗

Apolipoprotein E (APOE), PARKIN and catechol-O-methyltransferase (COMT) genes and susceptibility to sporadic Parkinson's disease in Finland.

Recent studies have demonstrated that genetic factors modify susceptibility to sporadic Parkinson's disease (PD). So far the results of candidate gene studies have been conflicting. It has been suggested that polymorphisms in apolipoprotein E (APOE), PARKIN and catechol-O-methyltransferase (COMT) genes might increase the risk of PD. We studied 147 Finnish non-demented patients with sporadic PD and 137 controls. APOE epsilon allele and genotype frequencies in PD patients did not differ significantly from controls. Three single nucleotide polymorphisms of the PARKIN gene and an intronic and an exonic (Val158Met) polymorphism of the COMT gene were studied. None of these polymorphisms showed association with PD in our series. In contrast to reports in oriental populations, our results do not support a major role of APOE, PARKIN and COMT polymorphisms in PD susceptibility in the Finnish population.

Adult↗

Release of soluble ICAM-5, a neuronal adhesion molecule, in acute encephalitis.

BACKGROUND: Intercellular adhesion molecule (ICAM)-5 (telencephalin) is an adhesion molecule in telencephalic neurons of the mammalian brain that binds to the leukocyte integrin CD11a/CD18. The authors observed that human cerebral neurons also expressed ICAM-5 and that ICAM-5--mediated neuron--leukocyte binding in cultured hippocampal neurons. This led the authors to examine ICAM-5 expression during clinical CNS inflammation. METHODS: The authors found, by immunoblotting, a 115-kDa soluble form of ICAM-5 (sICAM-5) cleaved from the membrane-bound (130 kDa) ICAM-5, and established an ELISA assay to measure it. CSF samples of patients with acute encephalitis and MS were studied. RESULTS: sICAM-5 was increased in encephalitis (320 plus minus 107 ng/mL; n = 25), as compared with patients with MS (128 plus minus 10 ng/mL; n = 16) and control subjects without CNS disease (137 plus minus 6 ng/mL; n = 42) (p < 0.001). The concentration of sICAM-5 correlated with the performance in the immediate recall task (p = 0.013) and with the leukocyte count in the CSF (p = 0.02), especially in cases caused by herpes simplex virus (HSV) (r = 0.94; p = 0.002). CONCLUSIONS: sICAM-5 is cleaved from CNS into CSF during acute encephalitis, and it may mediate leukocyte--neuron interactions. sICAM-5 release from cerebral neurons may actively regulate immune responses and leukocyte adhesion during microbial neuroinvasion in humans during encephalitis.

Acute Disease↗

Cognitive outcome in acute sporadic encephalitis.

Acute encephalitis is an inflammation of the brain parenchyma. In the United States, 20,000 cases occur yearly. A variety of cognitive deficits, often the sole cause of disability, may persist after the acute stage. Still, infectious diseases tend to be covered only briefly in neuropsychological handbooks. Recent literature demonstrates the heterogeneity of both amnestic disorders and the outcome following encephalitides. Herpes Simplex virus (HSV), the most common single etiology of sporadic encephalitis, usually causes the most severe symptoms. Modern antiviral medication, however, seems to improve the cognitive outcome. Much less is known about non-HSV encephalitides, where both mild and severe defects have been observed. This article summarizes the current knowledge and also calls upon a more active neuropsychological research in the area.

Acute Disease↗

Does glutamate mediate brain damage in acute encephalitis?

Cerebrospinal fluid (CSF) amino acid neurotransmitter concentrations in 23 patients with acute encephalitis were compared with those in patients with acute brain infarction, multiple sclerosis and controls. The concentration of glutamate was significantly higher in encephalitis (5.2+/-6.7 micromol/l) and stroke patients (9.6+/-14.2 micromol/l) than in MS patients (1.6+/-0.9 micromol/l) and controls (1.7+/-0.8 micromol/l; p < 0.001). The concentration of glycine was significantly higher in encephalitis (11.0+/-4.7 micromol/l) than in stroke (7.6+/-3.2 micromol/l) and MS patients (6.3+/-2.1 micromol/l) or controls (5.6+/-1.8 micromol/l; p < 0.002). Taurine levels were significantly lower in encephalitis patients than in the other groups (p = 0.04). The correlation of high glutamate levels with poor outcome was almost significant (Kendall tau 0.63, p = 0.06). Our observations suggest that exicitotoxic neurotransmission may play an important role in the series of events that lead to neuronal damage in encephalitis.

Adult↗

Neuromagnetic sequelae of herpes simplex encephalitis.

Spontaneous cortical activity and auditory evoked responses were recorded with a whole-scalp 122-channel neuromagnetometer from 4 patients after left-hemisphere dominant herpes simplex encephalitis and associated memory disorders. Spontaneous activity of one patient contained periodic sharp waves over the left hemisphere; the background activity was attenuated. The sources of periodic sharp waves clustered close to the sources of auditory evoked fields in the temporal lobe. In controls, dominant rhythmic activity over the parieto-occipital region had spectral maximum at 10.6 +/- 0.6 Hz; in patients the dominant rhythmic activity peaked at 8.6 +/- 1.8 Hz. The suppression of the parieto-occipital activity in eyes-open versus eyes-closed condition was smaller in patients than in controls. The patients' peak spectral frequency was correlated with neuropsychological tests reflecting deficient attentional capacity. The observed changes probably reflect decreased subcortical control of the cortical electric activity.

Adult↗

Is EEG useful in assessing patients with acute encephalitis treated with acyclovir?

EEG has been used widely in diagnosing encephalitis, as it demonstrates rather typical abnormalities, especially in herpes simplex virus encephalitis (HSVE). We analysed 204 EEG recordings from 98 consecutive acyclovir-treated patients with acute encephalitis between 1984 and 1994. Periodic complexes (PC) in the acute phase predicted poor outcome (Kendall tau 0.40, P < 0.001). However, unlike in many other diseases, e.g. stroke and intracerebral haemorrhage, the diffuse slowing of the background activity at acute phase did not predict outcome (Kendall tau -0.6, P = 0.35). At follow-up, the emergence of diffuse slow background activity was significantly associated with a less favourable outcome (Kendall tau 0.33, P = 0.0016). Among clinical variables, only epileptic seizures early during the course of the disease correlated significantly with outcome. EEG does have value as a prognostic indicator in acute encephalitides, but it seems that diffuse slowing of background activity or irritative features acutely are not as important as previously thought, based on the experiences of the pre-acyclovir era.

Acute Disease↗

Duration of transient amnesia correlates with cognitive outcome in acute encephalitis.

Temporary periods of amnesia are encountered in acute encephalitides. We investigated the association between transient encephalitic amnesia (TENA) and outcome in 60 patients. Twenty-six patients had TENA lasting < or = 1 day (short TENA), 17 had TENA lasting 2-7 days, and 17 had TENA for > 7 days (long TENA). The long TENA group had more neuropsychological impairment, larger brain lesions, and more difficulty in daily activities than the short TENA group. The findings were not explained by the number of epileptic seizures, delay of acyclovir medication, or the aetiology of encephalitis. TENA is a useful new clinical tool in predicting the outcome of acute encephalitis and selecting patients who are in need of detailed neuropsychological evaluation.

Acute Disease↗

Subcortical type cognitive impairment in herpes zoster encephalitis.

Nine immunocompetent patients with acute herpes zoster encephalitis (HZE) were studied with the help of neurological investigations. All patients were treated with acyclovir. Neuropsychological performance was compared with that of a group of 16 healthy controls. Computed tomography of the head showed infarct-like hypodense lesions in two patients, involving the internal capsule in one case and the temporoparietal cortex and white matter in another. Hypoperfusion shown by single photon emission computed tomography, mostly involving the frontal areas bilaterally, was seen in six of the seven patients examined. Hyperperfusion as seen in herpes simplex encephalitis was not encountered. One patient remained mildly demented, but all the other patients recovered relatively well. Neuropsychological examination after acyclovir treatment showed a decline in memory and speed of cognitive processes, without circumscribed neuropsychological deficits. Six of the nine patients showed behavioural disinhibition, and mood changes were also observed. Memory impairment in HZE was not as global or as severe as is described after encephalitis due to herpes simplex virus. In HZE both the brain perfusion pattern and the neuropsychological test profile showed features compatible with subcortical dysfunction.

Adult↗

Brain perfusion SPECT abnormalities in neuronal ceroid lipofuscinoses.

Brain perfusion was studied with the Tc-99m-HMPAO SPECT method in 19 INCL patients, 21 JNCL patients and 5 patients with Jansky-Bielschowsky variant disease (JBVD). The typical SPECT findings at an early stage of INCL were bilateral anterior frontal, posterior temporoparietal and occipital hypoperfusion, whereas reduction in cerebellar perfusion appeared later. However, perfusion of basal ganglia and thalami, although atrophic on MRI, was usually well preserved up to the terminal stage. All JNCL patients except one had at least one hypoperfused area. Mild hypoperfusion was usually located in the parietal and occipital lobes and cerebellum, whereas more severe hypoperfusion was observed in the temporal lobes. In JNCL, SPECT revealed lesions not detected on CT. All JBVD patients had supra- and infratentorial hypoperfusion, which was usually bilateral. This study shows that although in NCLs brain hypoperfusion can appear prior to structural abnormalities seen on MRI or CT, such abnormalities are not always associated with significant hypoperfusion.

Adolescent↗

Cognitive recovery instead of decline after acute encephalitis: a prospective follow up study.

OBJECTIVE: Follow up of cognitive sequelae of acute encephalitis and estimation of the frequency of persisting dementia. METHODS: Out of a series of 45 consecutive patients with acute encephalitis prospectively studied in 1990-95, 40 were screened for difficulty in everyday life using the Blessed dementia scale (BDS) 3.7 (1.4), mean (SD), years after onset. Eight patients had had herpes simplex encephalitis (HSVE), 16 some other identified aetiology, and in 21 the aetiology was unknown. All, except two patients with a nonherpetic encephalitis, were treated with acyclovir. All patients with disability in BDS (12/40), were invited to a neuropsychological reassessment, and the results of this assessment were compared with those of a similar assessment done after the acute stage. At follow up one patient could not complete the tests due to intractable epilepsy. RESULTS: In six of 11 cases the symptoms causing disability were mainly psychiatric. Five patients (two with HSVE) had a pronounced memory impairment together with other cognitive deficits, indicating dementia (frequency of 12.8%). In eight of the 11 testable cases cognitive performance had improved over the years, in two cases a decline was found and one patient with severe deficits showed no change. Intractable epilepsy was found in four of 12 cases. CONCLUSION: Cognitive decline had taken place already at the acute stage, and further deterioration was uncommon. Considerable improvement occurred in most patients during follow up. Also in patients with HSVE treated with acyclovir the cognitive recovery was substantial and of a magnitude not expected based on previous literature. Intractable epilepsy contributed to the cognitive deterioration in some cases. Affective disorders also had a surprisingly important role for the long term outcome.

Acute Disease↗

Unilateral hyperfusion in brain-perfusion SPECT predicts poor prognosis in acute encephalitis.

We studied 88 patients with acute encephalitis using hexamethylpropyleneamine oxime and single photon emission computed tomography (SPECT). All patients had been initially treated with intravenous acyclovir. The etiology could be disclosed in 37 patients (42%), which included 15 patients with herpes simplex encephalitis, 7 with varicella-zoster encephalitis, and 29 with other encephalitides (Mycoplasma, adenovirus, influenza, rotavirus, rubella, Epstein-Barr, arbovirus, syphilis, and tuberculosis). Unilateral hyperperfusion in SPECT was an independent predictor of poor prognosis, whereas neither clinical outcome variables, such as seizures, state of consciousness, and focal neurologic findings, nor CSF or EEG findings were not. Focal unilateral hyperperfusion is an indicator of severe inflammation of the brain tissue and predicts a poor outcome as assessed in terms of activities of daily living after recovery.

Acute Disease↗

Amnesia in acute herpetic and nonherpetic encephalitis.

OBJECTIVES: To evaluate how often global amnesia syndrome is encountered as a sequel of herpes simplex virus type 1 encephalitis (HSVE) and in other types of acute encephalitides, and to evaluate whether there are qualitative differences in amnesia caused by different encephalitides. SUBJECTS: Forty-five consecutive patients with encephalitis (mean age, 40.8 years) studied prospectively within a 5-year period, 8 of whom had HSVE. There were 24 normal controls. MEASURES: Neuropsychological assessment and memory evaluation after the acute stage of encephalitis, as well as at follow-up after 27.7 +/- 18.6 months. RESULTS: Three patients (6%), including 1 with HSVE, had persistent anterc grade and retrograde memory defects, typical features of global amnesia. Twelve patients had anterograde amnesia in the first assessment. No statistically significant differences in the memory measures were found between the HSVE (n = 4) and the non-HSVE (n = 8) groups. Some patients had predominantly semantic difficulty, some had a "frontal-type" memory disorder, and in some patients rapid forgetting was the prominent feature. CONCLUSIONS: The frequency of amnesia can reliably be evaluated only in consecutive series of patients. Previous literature, mainly case reports, may give the impression that global amnesia is a common consequence of encephalitis. Our findings do not support that view. Furthermore, there are clear differences in the quality of the memory impairment between cases of acute encephalitides. Our findings suggest that amnesia as a consequence of encephalitis, even HSVE, should not be considered a uniform phenomenon.

Acute Disease↗

Registration and display of brain SPECT and MRI using external markers.

Accurate anatomical localisation of abnormalities observed in brain perfusion single-photon emission computed tomography (SPECT) is difficult, but can be improved by correlating data from SPECT and other tomographic imaging modalities. For this purpose we have developed software to register, analyse and display 99mTc-hexamethylpropyleneamine oxime SPECT and 1.0 T MRI of the brain. For registration of SPECT and MRI data external skin markers containing 99mTc (220 kBq) in 50 microliters of coconut butter were used. The software is coded in the C programming language, and the X Window system and the OSF/Motif standards are used for graphics and definition of the user interface. The registration algorithm follows a noniterative least-squares method using singular value decomposition of a 3 x 3 covariance matrix. After registration, the image slices of both data sets are shown at identical tomographic levels. The registration error in phantom studies was on average 4 mm. In the two-dimensional display mode the orthogonal cross-sections of the data sets are displayed side by side. In the three-dimensional mode MRI data are displayed as a surface-shaded 3 D reconstruction and SPECT data as cut planes. The usefulness of this method is demonstrated in patients with cerebral infarcts, brain tumour, herpes simplex encephalitis and epilepsy.

Brain↗

Brain perfusion SPECT in juvenile neuronal ceroid lipofuscinosis.

The juvenile neuronal ceroid-lipofuscinosis (JNCL) is a recessively inherited progressive encephalopathy. We studied 21 JNCL patients with a duration of illness of 1 to 17 years by 99mTc-HM-PAO single photon emission computed tomography (SPECT) and correlated the findings with clinical parameters. All patients had at least one hypoperfused brain area, the median number of such areas was 5 per patient. Parietally, occipitally, and in the cerebellar lobes hypoperfusion was usually mild whereas it was temporally more severe. Right parietal hypoperfusion correlated to neurological dysfunction.

Adolescent↗