Mervi Pitkanen

Mapping the brain in younger and older asymptomatic HIV-1 men: Frontal volume changes in the absence of other cortical or diffusion tensor abnormalities

INTRODUCTION Over the past decade the developments made in treating people with human immune deficiency virus (HIV) have greatly improved quality of life and life expectancy. However, the nature of asymptomatic HIV-associated minor neurocognitive disorder (HAND) remains unclear. In this study we explored the occurrence of neuropsychological and neuroimaging changes in medically and psychiatrically stable HIV-1 infected patients on highly active antiretroviral treatment (HAART) from two separate age groups. METHODS Participants included 20 HIV-1 infected younger (aged 20-40) and 20 HIV-1 older patients (aged 50-75). Comparisons were made with 20 age- and education-matched younger and 22 matched older healthy seronegative males. Participants were stable on treatment and asymptomatic at study onset with undetectable HIV-1 viral loads, and free of medical or psychiatric co-morbidity, alcohol or substance misuse. A detailed neuropsychological assessment was used and volumetric-magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) performed to assess grey and white-matter integrity. RESULTS We found significant effects of ageing on memory, grey and white matter measures. Comparison of the HIV-positive and HIV-negative groups did not show significant differences on the neuropsychological tests after Bonferroni correction, and there were no significant age by HIV status interactions. However, we did find reduced grey matter volume on MRI in our HIV-positive participants within the medial and superior frontal gyri. We also found significant ageing effects in fronto-temporal grey and white matter, independent of the effect of HIV. CONCLUSIONS The results from this study suggest that HIV-1 disease by itself does not significantly impair cognitive function when patients are otherwise asymptomatic. Nevertheless, the imaging techniques were sensitive enough to detect subtle grey matter changes not normally evident until much later in the disease. If confirmed in a longitudinal study this frontal grey matter change could represent an important biomarker for trials in HIV disease.

Regional cerebral blood flow and FDG uptake in asymptomatic HIV‐1 men

Despite advances in the treatment of patients with human immunodeficiency virus (HIV), HIV‐associated neurocognitive disorder occurs in 15–50% of HIV‐infected individuals, and may become more apparent as ageing advances. In the present study we investigated regional cerebral blood flow (rCBF) and regional cerebral metabolic rate of glucose uptake (rCMRglc) in medically and psychiatrically stable HIV‐1‐infected participants in two age‐groups. Positron emission tomography (PET) and magnetic resonance imaging (MRI)‐based arterial spin labeling (ASL) were used to measure rCMRglc and rCBF, respectively, in 35 HIV‐infected participants and 37 HIV‐negative matched controls. All participants were currently asymptomatic with undetectable HIV‐1 viral loads, without medical or psychiatric comorbidity, alcohol or substance misuse, stable on medication for at least 6 months before enrolment in the study. We found significant age effects on both ASL and PET with reduced rCBF and rCMRglc in related frontal brain regions, and consistent, although small, reductions in rCBF and rCMRglc in the anterior cingulate cortex (ACC) in HIV, a finding of potential clinical significance. There was no significant interaction between HIV status and the ageing process, and no significant HIV‐related changes elsewhere in the brain on PET or ASL. This is the first paper to combine evidence from ASL and PET method in HIV participants. These finding provide evidence of crossvalidity between the two techniques, both in ageing and a clinical condition (HIV). Hum Brain Mapp 34:2484–2493, 2013.

Functional imaging correlates of fronto-temporal dysfunction in Morvan’s syndrome

A previously well 66-year-old man presented with a 1-month history of focal involuntary spasms of his arms and then his left leg, culminating in two generalised convulsions. He also complained of episodic memory problems, sleeping difficulties, daytime somnolence, hyperphagia, hyperhidrosis and erectile impotence. He was initially treated with phenytoin for 2 months and then valproate. His family noticed increasing dishevelment and emotional lability over the previous 6 months. Both he and his step-daughter reported that he did not drink to excess, although 10 years previously he was a heavy drinker, but had since cut down considerably. On examination, he was flamboyant, disinhibited and garrulous, but alert and orientated. He confabulated about attending to business and family affairs, whereas he had not worked for several years. He was able to learn a name and address perfectly in three attempts. He showed difficulties in naming people, word-finding and planning constructional tasks, which is indicative of fronto-temporal impairment. Cranial nerves were normal with no frontal release signs. There were prominent fasciculations bilaterally in quadriceps femorii, gastrocnemii and right biceps femoris. Power and coordination were normal. Deep tendon reflexes were absent except for biceps jerks. Plantar responses were flexor. Sensation was intact. The following blood tests …

Psychogenic amnesia: syndromes, outcome, and patterns of retrograde amnesia

&NA; There are very few case series of patients with acute psychogenic memory loss (also known as dissociative/functional amnesia), and still fewer studies of outcome, or comparisons with neurological memory‐disordered patients. Consequently, the literature on psychogenic amnesia is somewhat fragmented and offers little prognostic value for individual patients. In the present study, we reviewed the case records and neuropsychological findings in 53 psychogenic amnesia cases (ratio of 3:1, males:females), in comparison with 21 consecutively recruited neurological memory‐disordered patients and 14 healthy control subjects. In particular, we examined the pattern of retrograde amnesia on an assessment of autobiographical memory (the Autobiographical Memory Interview). We found that our patients with psychogenic memory loss fell into four distinct groups, which we categorized as: (i) fugue state; (ii) fugue‐to‐focal retrograde amnesia; (iii) psychogenic focal retrograde amnesia following a minor neurological episode; and (iv) patients with gaps in their memories. While neurological cases were characterized by relevant neurological symptoms, a history of a past head injury was actually more common in our psychogenic cases (P = 0.012), perhaps reflecting a ‘learning episode’ predisposing to later psychological amnesia. As anticipated, loss of the sense of personal identity was confined to the psychogenic group. However, clinical depression, family/relationship problems, financial/employment problems, and failure to recognize the family were also statistically more common in that group. The pattern of autobiographical memory loss differed between the psychogenic groups: fugue cases showed a severe and uniform loss of memories for both facts and events across all time periods, whereas the two focal retrograde amnesia groups showed a ‘reversed’ temporal gradient with relative sparing of recent memories. After 3–6 months, the fugue patients had improved to normal scores for facts and near‐normal scores for events. By contrast, the two focal retrograde amnesia groups showed less improvement and continued to show a reversed temporal gradient. In conclusion, the outcome in psychogenic amnesia, particularly those characterized by fugue, is better than generally supposed. Findings are interpreted in terms of Markowitschs and Kopelmans models of psychogenic amnesia, and with respect to Andersons neuroimaging findings in memory inhibition.

HIV: ageing, cognition and neuroimaging at 4 year follow-up

OBJECTIVES The aim of the study was to investigate the hypothesis of accelerated cognitive ageing in HIV-positive individuals using longitudinal assessment of cognitive performance and quantitative magnetic resonance imaging (MRI). METHODS We assessed a broad cognitive battery and quantitative MRI metrics [voxel-based morphometry (VBM) and diffusion tensor imaging (DTI)] in asymptomatic HIV-positive men who have sex with men (15 aged 20-40 years and 15 aged ≥ 50 years), and HIV-seronegative matched controls (nine aged 20-40 years and 16 aged ≥ 50 years). RESULTS Being HIV positive was associated with greater decreases in executive function and global cognition. Additionally, using DTI, we found that the HIV-positive group had a greater increase in mean diffusivity, but we did not find group differences in volume change using VBM. With respect to the HIV status by age group interaction, this was statistically significant for change in global cognition, with older HIV-positive individuals showing greater global cognitive decline, but there were no significant interaction effects on other measures. Lastly, change in cognitive performance was correlated with change in the DTI measures, and this effect was stronger for the HIV-positive participants. CONCLUSIONS In the present study, we found some evidence for accelerated ageing in HIV-positive individuals, with a statistically significant HIV status by age group interaction in global cognition, although this interaction could not be explained by the imaging findings. Moreover, we also found that change in cognitive performance was correlated with change in the DTI measures, and this effect was stronger for the HIV-positive participants. This will need replication in larger studies using a similarly lengthy follow-up period.

Case Study: Anti-GAD Encephalitis

A 58-year-old unemployed white lady was referred to the neuropsychiatry liaison team at a university hospital. She was admitted with confusion, auditory hallucinations, dehydration, malnutrition, upbeating nystagmus and ophthalmoplegia. She had been previously diagnosed with paranoid schizophrenia at the age of 40.