Jyrki Launes

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.

Neuropsychological sequelae of acute-onset sporadic viral encephalitis

Acute encephalitis is an inflammation of the brain parenchyma. In the USA, by estimation, 20,000 cases occur every year. A variety of cognitive deficits may persist after the acute stage, and they are often the sole cause of disability. Recent literature demonstrates the heterogeneity of both mnestic disorders and the outcome following encephalitis. Herpes simplex virus is the most commonly recognised single aetiology of sporadic encephalitis and it may be the cause of the most severe symptoms. Antiviral medication, however, seems to have improved the cognitive outcome when compared to the historical, untreated cases. The cognitive sequelae following herpes simplex virus encephalitis (HSVE) are best known and most commonly described, e.g., in textbooks, but they do not represent the typical symptomatology of encephalitis in general. Much less is unfortunately known about other types of encephalitis, those that account perhaps up to 80% of all cases, where both mild and severe defects have been observed. This article summarises the current knowledge.

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 99m Tc-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.

Subcortical type cognitive impairment in herpes zoster encephalitis.

Nine immunocompetent patients with acute herpes zoster encephalitis (HZE) were studied with the help of neurological, neuroradiological and neuropsychological 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 neurobehavioral outcome of hyperbilirubinemia in full term neonates—a 30 year prospective follow-up study

Background. Neonatal hyperbilirubinemia (HB) may cause severe neurological damage, but serious consequences are effectively controlled by phototherapy and blood exchange transfusion. HB is still a serious health problem in economically compromised parts of the world. The long term outcome has been regarded favorable based on epidemiological data, but has not been confirmed in prospective follow-up studies extending to adulthood. Methods. We studied the long term consequences of HB in a prospective birth cohort of 128 HB cases and 82 controls. The cases are part of a neonatal at-risk cohort (n = 1196) that has been followed up to 30 years of age. HB cases were newborns ≥ 2500 g birth weight and ≥ 37 weeks of gestation who had bilirubin concentrations > 340 µmol/l or required blood exchange transfusion. Subjects with HB were divided into subgroups based on the presence (affected HB) or absence (unaffected HB) of diagnosed neurobehavioral disorders in childhood, and compared with healthy controls. Subjects were seen at discharge, 5, 9 and 16 years of life and parent’s and teacher’s assessments were recorded. At 30 years they filled a questionnaire about academic and occupational achievement, life satisfaction, somatic and psychiatric symptoms including a ADHD self-rating score. Cognitive functioning was tested using ITPA, WISC, and reading and writing tests at 9 years of life. Results. Compared to controls, the odds for a child with HB having neurobehavioral symptoms at 9 years was elevated (OR = 4.68). Forty-five per cent of the HB group were affected by cognitive abnormalities in childhood and continued to experience problems in adulthood. This was apparent in academic achievement (p < 0.0001) and the ability to complete secondary (p < 0.0001) and tertiary (p < 0.004) education. Also, the subgroup of affected HB reported persisting cognitive complaints e.g., problems with reading, writing and mathematics. Childhood symptoms of hyperactivity/impulsivity (p < 0.0001) and inattention (p < 0.02) were more common in HB groups, but in adulthood the symptoms were equal. The affected HB had lower scores in parameters reflecting life satisfaction, less controlled drinking, but not increased substance abuse. Discussion. Our results indicate that neonatal HB has negative consequences in adult age. A prospectively collected cohort with strict inclusion criteria enables to control most of the bias factors involved with retrospective data. The control and HB groups were remarkably similar at birth in terms of medical data, and the growth environment of the children, as well as the parents’ social groups, education, size of family, type of housing at birth and at 9 years of age. Our findings bear resemblance to disorders of the fronto-striatal network, and also symptoms of the ADHD spectrum were frequent in the HB group suggesting a link of HB to other neurodevelopmental disorders.

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.

Validation of quantitative brain dopamine D2 receptor imaging with a conventional single-head SPET camera

Phantom measurements were performed with a conventional single-head single-photon emission tomography (SPET) camera in order to validate the relevance of the basal ganglia/frontal cortex iodine-123 iodobenzamide (IBZM) uptake ratios measured in patients. Inside a cylindrical phantom (diameter 22 cm), two cylinders with a diameter of 3.3 cm were inserted. The activity concentrations of the cylinders ranged from 6.0 to 22.6 kBq/ml and the cylinder/background activity ratios varied from 1.4 to 3.8. From reconstructed SPET images the cylinder/ background activity ratios were calculated using three different regions of interest (ROIs). A linear relationship between the measured activity ratio and the true activity ratio was obtained. In patient studies, basal ganglia/frontal cortex IBZM uptake ratios determined from the reconstructed slices using attenuation correction prior to reconstruction were 1.30±0.03 in idiopathic Parkinsons disease (n=9), 1.33±0.09 in infantile and juvenile neuronal ceroid lipofuscinosis (n=7) and 1.34±0.05 in narcolepsy (n=8). Patients with Huntingtons disease had significantly lower ratios (1.09±0.04, n=5). The corrected basal ganglia/frontal cortex ratios, determined using linear regression, were about 80% higher. The use of dual-window scatter correction increased the measured ratios by about 10%. Although comprehensive correction methods can further improve the resolution in SPET images, the resolution of the SPET system used by us (1.52 cm) will determine what is achievable in basal ganglia D2 receptor imaging.

Attrition in a 30-year follow-up of a perinatal birth risk cohort: factors change with age

Background. Attrition is a major cause of potential bias in longitudinal studies and clinical trials. Attrition rate above 20% raises concern of the reliability of the results. Few studies have looked at the factors behind attrition in follow-ups spanning decades. Methods. We analyzed attrition and associated factors of a 30-year follow-up cohort of subjects who were born with perinatal risks for neurodevelopmental disorders. Attrition rates were calculated at different stages of follow-up and differences between responders and non-responders were tested. To find combinations of variables influencing attrition and investigate their relative importance at birth, 5, 9, 16 and 30 years of follow-up we used the random forest classification. Results. Initial loss of potential participants was 13%. Attrition was 16% at five, 24% at nine, 35% at 16 and 46% at 30 years. The only group difference that emerged between responders and non-responders was in socioeconomic status (SES). The variables identified by random forest classification analysis were classified into Birth related, Development related and SES related. Variables from all these categories contributed to attrition, but SES related variables were less important than birth and development associated variables. Classification accuracy ranged between 0.74 and 0.96 depending on age. Discussion. Lower SES is linked to attrition in many studies. Our results point to the importance of the growth and development related factors in a longitudinal study. Parents’ decisions to participate depend on the characteristics of the child. The same association was also seen when the child, now grown up, decided to participate at 30 years. In addition, birth related medical variables are associated with the attrition still at the age of 30. Our results using a data mining approach suggest that attrition in longitudinal studies is influenced by complex interactions of a multitude of variables, which are not necessarily evident using other multivariate techniques.

The Perinatal Adverse events and Special Trends in Cognitive Trajectory (PLASTICITY) - pre-protocol for a prospective longitudinal follow-up cohort study

Prospective follow-up studies on long term effects of pre- and perinatal adverse conditions in adulthood are rare. We will continue to follow the prospective cohort of initially 1196 subjects with predefined at-delivery risk factors out of 22,359 consecutive deliveries during 1971-74 at a single maternity hospital. The risk cohort and 93 controls have been followed up with a comprehensive clinical program at 5, 9, and 16 years of age and by questionnaire at the age of 30 years. Major medical events known to affect the development and growth of the brain, or cognitive functions and personality have been documented. Here we present a pre-protocol for the project, which we will call PLASTICITY, whose aim is to follow consenting subjects and controls into mid-adulthood and beyond, and to explore how the neonatal risk factors modulate neurodevelopmental and neurodegenerative processes such as learning disabilities, ADHD, aging, early onset mild cognitive impairment and even dementia. Our first focus is on the neurological and cognitive outcomes at age 40 years, using detailed neurological, neuropsychological, neuroimaging, genetic, blood chemistry and registry based methods. Results will be expected to offer information on the risk of neurological, psychiatric, metabolic and other medical consequences as well as the need for health and social services at the brink of middle age, when new degenerative phenomena are known to emerge. The evaluation at age 40 years will serve as a baseline for later aging studies. We welcome all comments and suggestions, which we will apply in finalizing details and inviting collaboration.

Adult with Middle Interhemispheric Variant of Holoprosencephaly: Neuropsychological, Clinical, and Radiological Findings.

OBJECTIVEnThe middle interhemispheric variant of holoprosencephaly (MIHV) is a mild, rare variant of holoprosencephaly. Only a few cases of children with MIHV have been reported. Here we report in detail an adult case.nnnMETHODnThe patient is a female in her 30s. The patient underwent an extensive neuropsychological examination, a neurological examination and a magnetic resonance imaging.nnnRESULTSnNeuroradiologically, the patient had a typical finding of MIHV, with the absence of the central corpus callosum and union of posterior frontal and anterior parietal gyri. In neuropsychological examination, the patient had average or above average performance in verbal comprehension, naming, reading and writing, and below average performance in perceptual reasoning, visuospatial abilities, processing speed and memory. Also difficulties in mathematical abilities, psychomotor skills, and executive functions were found. No gross neurological involvement was noted. She was diagnosed with atypical depression, post-traumatic stress disorder and a dissociative disorder in early adulthood. Despite cognitive deficits, she was able to achieve a tertiary level education.nnnCONCLUSIONSnThis is the first adult case of MIHV described in detail. Our case emphasizes the possibility of a missed diagnosis of marked brain malformations in patients with craniofacial abnormalities. More cases and prospective follow-up studies are needed to understand the evolvement of both neuropsychological and psychiatric symptoms in these patients.