Biomedical subjects

L Hokkanen

Publications and source records attributed to L Hokkanen.

At least 19 recordsLinked to original sources

PubMed2006

The PASAT performance among patients with multiple sclerosis: analyses of responding patterns using different scoring methods.

The Paced Auditory Serial Addition Test (PASAT) is widely used in the evaluation of multiple sclerosis (MS) patients' cognitive performance, and also used as the sole measure of cognition in a recently developed assessment tool for MS clinical trials, the Multiple Sclerosis Functional Composite (MSFC). We analysed if MS patients and healthy controls have different patterns of responding in the PASAT, and whether different scoring methods influence the PASAT's sensitivity and specificity in detecting disease-associated cognitive impairment. Forty-five relapsing-remitting MS patients and 48 healthy controls were evaluated using the PASAT and a comprehensive neuropsychological examination. Cognitively deteriorated MS patients compensated for their difficulties in PASAT by omitting rather than guessing answers. They skipped items intermittently, which reduces the difficulty of the task. Furthermore, towards the end of the PASAT's 60-item series MS patients' performance had a trend to fade whereas controls' performance was more even throughout the task. The dyad score or the percent dyad score did not essentially improve the sensitivity or the specificity, but the accuracy improved when the answers at the end of the PASAT series were specifically emphasized. Using the combined score, 73% of the patients were correctly classified as cognitively impaired or unimpaired.

Adult↗

PubMed2002

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↗

PubMed2001

Response of the QT interval to mental and physical stress in types LQT1 and LQT2 of the long QT syndrome.

OBJECTIVE: To study and compare the effects of mental and physical stress on long QT syndrome (LQTS) patients. DESIGN: Case-control study. MAIN OUTCOME MEASURES: QT intervals were measured from lead V3. Serum potassium and plasma catecholamine concentrations were also monitored. PATIENTS: 16 patients with type 1 LQTS (LQT1), 14 with type 2 LQTS (LQT2), both groups asymptomatic, and 14 healthy control subjects. INTERVENTIONS: Three types of mental stress tests and a submaximal exercise stress test. RESULTS: Heart rate responses to mental stress and exercise were similar in all groups. During mental stress, the mean QT interval shortened to a similar extent in controls (-29 ms), LQT1 patients (-34 ms), and LQT2 patients (-30 ms). During exercise, the corresponding QT adaptation to exercise stress was more pronounced (p < 0.01) in healthy controls (-47 ms) than in LQT1 (-38 ms) or LQT2 patients (-38 ms). During exercise changes in serum potassium concentrations were correlated to changes in QT intervals in controls, but not in LQTS patients. LQT1 and LQT2 patients did not differ in serum potassium, catecholamine or heart rate responses to mental or physical stress. CONCLUSIONS: QT adaptation to mental and exercise stress in healthy people and in patients with LQTS is different. In healthy people QT adaptation is more sensitive to physical than to mental stress while no such diverging pattern was seen in asymptomatic LQTS patients.

Adolescent↗

PubMed2000

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↗

PubMed1998

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↗

PubMed1998

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↗

PubMed1998

Modification of neuromagnetic cortical signals by thalamic infarctions.

Auditory evoked responses and spontaneous cortical activity were recorded with a whole-scalp 122-channel neuromagnetometer from 7 patients, who had small thalamic infarctions in the region of the left anterior tuberothalamic artery and associated memory defects. In contrast to healthy control subjects, with dominant rhythmic activity at 10.6 +/- 0.6 Hz in the parieto-occipital region, the spectral maximum in the patients was at 8.9 +/- 0.4 Hz. Abnormal acceleration of rhythmic activity was also observed bilaterally in rolandic areas. Our findings imply that lesions of non-specific thalamic nuclei may disturb human brain rhythms in widespread cortical areas. 'Mismatch responses' to deviant tones (1.1 kHz) among standards (1.0 kHz), suggested to reflect sensory auditory memory in healthy subjects, were absent in 2 patients, markedly decreased in 3, and normal in 2, implying that pathways passing through the anteromedial thalamus contribute to modulation of these responses. We conclude that local unilateral lesions in the anteromedial thalamus may cause extensive, bilateral alterations in the brain's electric activity.

Adult↗

PubMed1997

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↗

PubMed1997

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↗

PubMed1997

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↗

PubMed1996

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↗

PubMed1996

Cognitive impairment after acute encephalitis: comparison of herpes simplex and other aetiologies.

OBJECTIVE: To compare the cognitive defects after acute acyclovir treated herpes simplex encephalitis with those after other types of acute encephalitis. METHODS: Seventy seven consecutive patients between 1985 and 1995 and 29 normal controls were studied. Of the 77 patients without concomitant neurological conditions, 17 had herpes simplex, one virus encephalitis (HSVE group), 27 had some other identified aetiology (non-HSVE group), and in 33 patients the cause was unknown. Acyclovir treatment was started less than four days after the first mental symptoms in 12 of 17 patients with HSVE. A thorough neuropsychological assessment was carried out about one month after the onset. RESULTS: The HSVE group had deficits in verbal memory, verbal-semantic functions, and visuoperceptual functions more often than the non-HSVE group. The risk for cognitive defects was twofold to four-fold in the patients with HSVE compared with the non-HSVE patients. Two (12%) of the patients with HSVE and 12 (44%) of the non-HSVE patients were cognitively intact. Six patients with HSVE (46%) and 17 (89%) non-HSVE patients later returned to work. The lesions on CT or MRI were bilateral only in one patient with HSVE. The defects in the three patients with adenovirus infection were severe and resembled the amnesia after HSVE. Cognitive impairment, not previously reported, was found in encephalitis after rotavirus infection and epidemic nephropathy. CONCLUSION: The recovery in the HSVE group was better than expected based on the medical literature. On the other hand there were surprisingly severe cognitive defects in encephalitis after other viruses. With early acyclovir treatment patients with the least severe HSVE were equivalent to those with non-HSV encephalitis with good outcome whereas those with the most severe non-HSV encephalitis were equivalent to those with HSVE with poor outcome.

Acute Disease↗

PubMed1995

Hyperfixation of 99mTc-HMPAO and hypofixation of 123I-iomazenil in acute herpes encephalitis.

We studied two patients with herpes encephalitis (HSE) by [99mTc]HMPAO and [123I]iomazenil single photon emission computed tomography. Increased uptake of HMPAO was seen for up to 63 days in the HSE affected brain area. Iomazenil binds to benzodiazepine receptors and can measure neurone loss. Decreased iomazenil uptake was observed a few days after onset, at a time when hyperfixation of HMPAO occurred. Because in HSE neurone loss occurs simultaneously with hyperfixation of HMPAO, it is unlikely that this hyperfixation is caused by increased neuronal activity, as in epilepsy. This suggests that the hyperfixation of HMPAO in HSE occurs in glia and is sustained by inflammation-related hypermetabolism and acidity. The early neurone loss in HSE stresses the importance of immediate antiviral treatment.

Brain↗

PubMed1995

Isolated retrograde amnesia for autobiographical material associated with acute left temporal lobe encephalitis.

Retrograde amnesia for autobiographical material in the absence of anterograde amnesia or other memory disturbances was found in a patient with acute viral encephalitis. Memory loss showed a temporal gradient, but new learning was spared. Both brain perfusion imaging with 99mTc-HMPAO SPECT, and EEG localized the lesion in the left temporal lobe while CT and MRI were normal. This observation supports the anatomical differentiation between the different memory functions. The uncommon combination of isolated retrograde amnesia without other neuropsychological findings may raise the doubt of psychogenic aetiology, which in this case was refuted.

Adult↗

PubMed1994

Zidovudine reduces intrathecal immunoactivation in patients with early human immunodeficiency virus type 1 infection.

OBJECTIVE: To evaluate the effect of zidovudine on human immunodeficiency virus type 1 (HIV-1)-associated central nervous system infection in Centers for Disease Control and Prevention stage II or III disease. DESIGN: In an open-ended trial, patients received 500 mg of zidovudine twice a day for 12 months. Lumbar punctures, neurological, neuropsychological, and neuroradiological examinations were repeatedly performed during the trial period and were compared with pretrial values. In 11 patients post-trial neurological follow-up of 10 to 20 months was performed. PATIENTS: Initially, 14 volunteers with stage II or III disease and intrathecal synthesis of HIV-1-specific antibodies were enrolled. Additionally, patients had slight neuropsychological disturbance or brain atrophy unrelated to other agents than HIV-1. Two patients dropped out because of poor compliance. MAIN OUTCOME MEASURES: Intrathecal and systemic immune and virological responses, cognitive performance, and brain images were repeatedly monitored. RESULTS: After 6 weeks of zidovudine therapy, initial low-grade pleocytosis and elevated levels of beta 2-microglobulin, both in cerebrospinal fluid and in serum samples, declined. Intrathecal HIV-1 antibody synthesis could no longer be detected in half of the patients after 12 months of zidovudine therapy. Patients with defective cognition transiently improved cognitive speed and flexibility after 6 months of therapy. Slight atrophic brain changes, however, remained unchanged. CONCLUSIONS: Zidovudine reduces intrathecal immuno-activation and transiently improves cognitive functioning in HIV-1-infected subjects who show evidence of central nervous system involvement by HIV-1 but are otherwise asymptomatic.

Adult↗

PubMed1994

Reversible cognitive decline during high-dose alpha-interferon treatment.

The cognitive effects of high-dose human leukocyte alpha-interferon (IFN-alpha) treatment were evaluated among 15 patients with the newly diagnosed spinal form of amyotrophic lateral sclerosis (ALS). To confirm the earlier findings showing reversible effects on cognitive performance and to exclude confounding effects, a randomized blinded placebo controlled study was conducted. Twelve patients with continuous intravenous IFN-alpha-infusion treatment over five days and 3 placebo control patients were neuropsychologically evaluated. The neuropsychological examination included tests of intelligence, memory, complex mental processing, visuoconstructional skills, writing, and calculation. A clear difference in the performance profiles of the placebo and the IFN-alpha-treated patient groups was detected: The IFN-alpha group showed significant deterioration during treatment in the digit span backwards task, logical verbal memory task, calculation ability, and writing time, while improvement was seen after treatment. Concomitant fever did not explain the findings. In the placebo group an improvement indicating a learning effect in the three consecutive measurements was found. The reversible cognitive deterioration indicates a clear CNS effect during the IFN-alpha treatment.

Adult↗

PubMed1993

Cognitive performance in HIV-1 infection: relationship to severity of disease and brain atrophy.

We examined cognitive performance in 72 HIV-1 infected patients and 34 controls. None of the patients had opportunistic infections or unusual neoplasms of the central nervous system (CNS). Factors other than HIV-1 known to cause cognitive decline were excluded from both groups. Cognitive functioning analysed with special emphasis on the severity of HIV infection was related to neuroradiological and immunological findings. In patients with AIDS-related complex (CDC IVa) or AIDS (CDC IVc,d), a deterioration of memory as well as cognitive speed and flexibility was detected. Furthermore, memory deficits were associated with central cerebral and infratentorial atrophy in those patients, while no association was found between cognitive deficits and immunological abnormalities. Patients at CDC stages II or III showed slight association between altered cognitive speed and flexibility and elevated leukocyte count, suggesting a subclinical CNS disease already at early stages of HIV infection.

AIDS Dementia Complex↗

PubMed1993

CSF follow-up in HIV-1 infection: intrathecal production of HIV-specific and unspecific IGG, and beta-2-microglobulin increase with duration of HIV-1 infection.

Ninety-nine sequential cerebrospinal fluid (CSF) samples from 28 human immunodeficiency virus-1 (HIV-1)-infected patients were analyzed during the follow-up of 9 months to 4 years. Intrathecal synthesis of HIV-antibodies and IgG (p < 0.01), and the levels of beta-2-microglobulin (beta 2m) in the CSF (p < 0.05) and serum (p < 0.01) increased with duration of HIV-1 infection. No effect of duration of HIV-1 infection was observed on the individual CSF white cell counts and the levels of blood-brain-barrier (BBB) permeability. In 13 patients with HIV-1-associated central nervous system (CNS) disease, the effect of duration was seen as an increase of the individual beta 2m levels in serum (p < 0.01). Moreover, 7 of 9 patients who developed neurological disease or showed its progression during the study increased the level of beta 2m in the CSF. All of them increased the level of beta 2m in serum. In 15 neurologically healthy subjects, the effect of duration was expressed as an increase of the level of individual beta 2m in CSF (p < 0.05) and intrathecal IgG synthesis (p < 0.01). In the AIDS group, the level of beta 2m in the CSF increased, but in less severe stages the dependency of the individual CSF parameters on disease duration was not found. Our results indicate that elevated levels of beta 2m in CSF and serum appear to predict progression of neurological and systemic diseases, respectively. Elevated beta 2m in the CSF of clinically intact individuals may indicate subclinical neurological disease caused by HIV-1.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS Dementia Complex↗