A. A. Möller

Nocturnal sleep in huntington's disease

SummaryNocturnal sleep was studied in 16 inpatients with Huntingtons disease. In comparison with healthy controls, patients exhibited a disturbed sleep pattern with increased sleep onset latency, reduced sleep efficiency, frequent nocturnal awakenings, more time spent awake and less slow wave sleep. These abnormalities correlated in part with duration of illness, severity of clinical symptoms, and degree of atrophy of the caudate nucleus. Patients showed an increased density of sleep spindles.

Increased endogenous interferon-gamma and neopterin correlate with increased degradation of tryptophan in human immunodeficiency virus type 1 infection

Reduced tryptophan and increased kynurenine concentrations have been reported in patients with human immunodeficiency virus type 1 (HIV-1) infection. From in vitro data it appears that activated indoleamine 2,3-dioxygenase (IDO) is involved in this metabolic change. IDO is inducible by interferon-(IFN)-gamma. We compared serum concentrations of IFN-gamma and neopterin (the biosynthesis of which is also inducible by IFN-gamma) with serum, tryptophan and kynurenine of 42 patients with HIV-1 infection. IFN-gamma, neopterin and kynurenine levels were significantly increased compared to HIV-1 seronegative controls whereas tryptophan was significantly decreased. Various significant correlations were found between tryptophan, kynurenine, IFN-gamma and neopterin concentrations. Highest degree of correlation was found between neopterin, IFN-gamma and the kynurenine per tryptophan quotient which is the ratio between the product and the substrate concentration of IDO. The data indicate that decreased tryptophan in HIV-1 seropositives may result from chronic immune activation and can be referred to increased activation of IDO.

Nocturnal sleep EEG in patients with HIV infection

SummaryNocturnal sleep was studied in 14 human immunodeficiency virus (HIV)-positive patients without opportunistic infections of the central nervous system. Seven patients had no bodily complaints at the time of the investigation. Patients exhibited an impaired nocturnal sleep with longer sleep onset latency, reduced total sleep time, reduced sleep efficiency, and more time spent awake and in stage 1. Stage 2 sleep was significantly decreased; in 2 cases, sleep spindle density was extremely low. REM latency was reduced and correlated negatively with depressive symptomatology, while the percentages of REM and slow wave sleep were normal. No significant differences in sleep parameters were present among patients in different stages of the illness, or between patients with and without bodily complaints. Ventricular size and sulcal width on computed tomography scans correlated with sleep variables indicating reduced sleep quality, and with REM density. Decreased tryptophan plasma levels were associated with shorter and less efficient sleep, and with reduced stage 2 sleep. The findings demonstrate that sleep EEG investigations can be valuable for detecting and monitoring central nervous system affection in HIV-positive individuals.

Alterations of nocturnal sleep in patients with HIV infection

Nocturnal sleep of 14 patients with HIV infection was characterized by longer sleep onset latency, shorter total sleep time, reduced sleep efficiency, more time spent awake and in Stage 1. There was significantly less sleep Stage 2 than in healthy controls. REM latency was slightly reduced and correlated negatively with depressive symptomatology, while percentages of REM and slow wave sleep were normal. Patients without complaints at the time of the investigation exhibited similar sleep abnormalities. The results stress the usefulness of polysomnography as a sensitive methodology for detection and monitoring of CNS affection in HIV positive patients.

The stereotactic biopsy diagnosis of focal intracerebral lesions in AIDS patients.

Focal intracerebral lesions were biopsied stereotactically in 23 adult HIV‐infected patients, the main indication for which was the failure to respond to anti‐toxoplasma treatment. A cerebral disease was the initial or main complaint in 19 of them. In 22 of 25 stereotactic approaches, a clear‐cut morphological diagnosis could be established (9 primary brain lymphoma, 7 necrotizing toxoplasma encephalitis, 5 progressive multifocal leukoencephalopathy, 1 HIV encephalitis, 3 unspecific tissue changes). In 7 of 8 deceased patients, autopsy confirmed the bioptical diagnosis. The high diagnostic yield was related to the strategy of the stereotactic method and the sample size (3 to 4 consecutive samples along the stereotactic track including the marginal zones, 1 cm long tissue cylinders). Formalin fixation and paraffin embedding of the samples provide the possibility of serial sections and special stainings (immunohistochemistry, in‐situ hybridization) and kill the HIV. Stereotactic brain biopsy is a highly accurate diagnostic tool to ascertain the nature of focal intracerebral lesions in selected AIDS patients.

Brain morphology and sleep EEG in patients with Huntington's disease.

SummaryIn 12 patients with Huntingtons disease, the relationship between brain morphology, nocturnal sleep EEG, and clinical variables was studied. Global cerebral atrophy did not significantly correlate with sleep parameters, whereas atrophy of the caudate nuclei was associated with reduced slow wave sleep and increased time spent awake. Several clinical parameters (e.g., anergia and thought disturbance scores of the Brief Psychiatric Rating Scale, illness duration and global clinical assessment) showed significant correlations with global cerebral atrophy. Similar studies in other neuropsychiatric disorders demonstrate associations between sleep alterations and brain morphological changes of different localizations, thus pointing to a complex relationship between both. It can be hypothesized that the caudate nuclei may be involved in sleep regulation; indirect evidence from studies with positron emission tomography (PET) point in the same direction.

Neopterin Production, Degradation of Tryptophan and Neurologic Impairment in Human Immunodeficiency Virus Infection

Abstract Neurologic impairment In human immunodeficiency virus (HIV) infection may be related to metabolic factors in addition to a direct effect of HIV in the brain. An immune-enhanced tryptophan catabolism has been described in HIV infected patients that may contribute to neurologic/ psychiatric symptoms. In 41 HIV-infected patients we studied the serum and cerebrospinal fluid concentrations of interferon-γ, neopterin, tryptophan and kynurenine in comparison to determinations of neurologic and psychiatric abnormalities as measured by a mental test and computerized tomography. Serum concentrations of interferon-γ, neopterin, and kynurenine were increased, whereas tryptophan levels were de creased in patients. Similarly, cerebrospinal fluid concentrations of neopterin and kynurenine were increased in the majority of patients compared to normal values. Significant relations existed between serum neopterin, tryptophan and its degradation product kynurenine and neurologic parameters. In cerebrospinal fluid , concentrations of neopterin but not of the other parameters tested were related to the mental state of patients. Our study demonstrates that systemic immune activation and its influence on tryptophan metabolism are related to neurologic disease in HIV patients. Intrathecal alterations of tryptophan and kynurenine appear to be less important.