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.

Cognitive impairment, dementia and psychosocial functioning in human immunodeficiency virus infection. A prospective study based on DSM-III-R and ICD-10.

Progressive cognitive impairment in human immunodeficiency virus (HIV) infection, called acquired immunodeficiency syndrome (AIDS) dementia complex (ADC), significantly influences the social prognosis of afflicted patients. The frequency and character in different stages of the infection are controversially discussed. In previous studies, differences in the selection of patients and methods of testing led to widely differing results. For these reasons, in the present prospective study on 45 HIV-infected patients, a structured psychiatric interview (SIDAM) was conducted based on the algorithm of diagnosing dementia in DSM-III-R and the ICD-10 guidelines. The psychopathological findings are expressed in syndrome scores; the results are summarized in a total score (SISCO). The interview contains the Mini-Mental State Examination. The degree of psychosocial functioning was estimated on the global assessment of functioning, Axis V of DSM-III-R. In stages preceding AIDS, only slight cognitive dysfunction was found compared with age- and education-matched normal controls, and this caused no relevant disturbance of psychosocial functioning. In 9 patients with manifest AIDS, dementia was diagnosed with DSM-III-R criteria and ICD-10 guidelines (30% of the AIDS patients). They showed marked impairment of intellectual ability, memory, verbal ability and calculation and constructional ability and fewer cortical focal symptoms (aphasia and apraxia). Corresponding to previous studies, major cognitive dysfunction in HIV infection can be characterized as subcortical dementia.

[Subacute progressive polyneuropathy syndrome in HIV infection. The efficacy of immunosuppressive treatment?]. / Subakut progredientes Polyneuropathiesyndrom bei HIV-Infektion. Wirksamkeit der immunsuppressiven Behandlung?

A subacute advanced severe sensorimotor polyneuropathy developed over 6 months in a 47-year-old patient in stage 5 of an HIV infection (Walter Reed Hospital classification). Clinical examination, cranial computed tomography and spinal nuclear magnetic imaging failed to demonstrate any central nervous system complication. Cerebrospinal fluid showed a lymphocytic pleocytosis of 57/3 cells and total protein raised to 132 mg/dl as sign of an abnormal blood-brain barrier. Circulating immune complex in blood was raised to 30%. Assuming an immune-complex mediated neuropathy treatment with oral steroids was started, initially 150 mg daily. The signs of polyneuropathy regressed almost completely, even after prednisolone was discontinued. The proportion of circulating immune complexes in blood fell within 7 weeks to 10% during this treatment. It is suggested that in HIV-infected patients severe polyneuropathies may develop as part of a humoral immune reaction in which immunosuppressive treatment can be effective. Even in advanced HIV infection high-dosage and prolonged steroid treatment can be undertaken, under strictest indications, and may have impressive results.

[Incidence of psychiatric syndromes and the psychosocial functional level of patients with HIV-1 infection]. / Häufigkeit psychiatrischer Syndrome und psychosoziales Funktionsniveau im Verlauf der HIV-1-Infektion.

There are not yet unselected studies on psychopathological syndromes in the course of HIV-infection in German-speaking countries. In a group of 55 patients in different stages of the infection two psychiatric explorations were done within an interval of about one year. The findings were analysed by the Brief Psychiatric Rating Scale (BPRS). The degree of psychosocial functioning was estimated using the GAF-scale (axis 5 of DSM-III-R). The diagnosis of dementia was based on DSM-III-R-criteria. Most of the patients (72%) showed normal or only slightly remarkable psychopathologic findings at both times. A significant increase in psychopathologic conspicuousness in the course of the disease was only found for the subscore BPRS 2 ("anergia"). Dementia was seen in five patients (9%) and only in the stage of manifest immune deficiency syndrome (WR 6). All-together there was only a slight decrease of psychosocial functioning detectable (median on the GAF-scale 75), which only in dementia showed a significant reduction.

Nocturnal sleep in Huntington's disease.

Nocturnal sleep was studied in 16 inpatients with Huntington's 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.

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.

[Disorders of the afferent visual pathway in HIV infection. 1. Optic nerve and 2. Visual pathways/visual cortex]. / Erkrankungen der afferenten Sehbahn bei HIV-Infektion. 1. Sehnerv und 2. Sehstrahlung/Sehrinde.

Up to now little involvement of the afferent visual pathway (optic nerve and optic radiation and visual cortex) in HIV infection has been apparent. These results are based on our prospective investigations of 538 HIV-infected individuals, among them 261 patients with full-blown AIDS carried out by the same examiner over a 6-year period (1984-1990). Diseases of the optic nerve were observed in 22/261 (8.4%) of Aids patients but in only 1/227 (0.4%) of patients with earlier stages of HIV infection. Optic neuritis was the most common disease (in 14/261 = 5.4% of Aids patients), for the most part occurring in the course of CMV (cytomegalovirus) retinitis. For this form the prognosis was primarily good under virustatic therapy with ganciclovir in contrast to primary CMC papillitis. Furthermore, a few cases of optic perineuritis, optic neuropathy in basal meningitis, ischemic optic neuropathy and papilloedema with increased intracranial pressure were observed, most of them caused by opportunistic infections of the central nervous system. In single cases the HIV might hypothetically have played a role in the etiology. Visual impairment of the patients varied from subtle disturbances to blindness. Often optic atrophy resulted. Homonymous hemianopsia was the principal sign in diseases of the visual pathway between the lateral geniculate body and the visual cortex (in 10/261 = 3.8% of Aids patients). This symptom resulted from cerebral toxoplasmosis in 7 cases, progressive multifocal leukoencepalopathy (PML) in 2 cases and primary intracerebral malignant lymphoma in 1 case. The visual fields and neuroradiological findings are demonstrated. In 3 cases the homonymous hemianopsia was the first clinical appearance of Aids. Involvement of the afferent visual pathway in HIV infection may be a cause of blindness or visual disturbances despite normal findings on examination of the eyes themselves.

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

In 12 patients with Huntington's 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.

Nocturnal sleep EEG in patients with HIV infection.

Nocturnal 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.

CT findings in different stages of HIV infection: a prospective study.

In the acquired immunodeficiency syndrome (AIDS), different patterns of CT findings have been described. In a prospective and unselected CT study we examined 200 patients in different stages of HIV-1 infection, 14% of whom had focal lesions, 37% atrophic changes and 49% normal findings. The differential diagnosis is discussed. Depending on the patient's complaints and clinical findings, even when the CT scan is normal there may be treatable complications that must be detected by other diagnostic techniques, such as lumbar puncture.

[Psychological disorders in epilepsy]. / Psychische Störungen bei Epilepsie.

Thirty-two patients with idiopathic grand mal, and 32 patients with psychomotor seizures were investigated for interictic mental changes. The assessment by the information provided by the patients themselves were entered into the symptom scales of the Inpatient Multidimensional Psychiatric Scale (IMPS). Some 40% of the patients, with no significant differences between the groups, reveal signs of depression in the IMPS. In comparison with available IMPS group profiles, the depressive disorder proves moderate corresponding rather to the organic or neurotic scale score than to the score achieved by patients with endogenous depression. The incidence of seizures and determinable childhood behavioral disturbances were found to be parameters that had a significant influence on the psychopathological finding, but not the duration of the condition or age at onset.

[Depressive disorder of the epilepsy patient--symptoms and factors of influence]. / Zur Depressivität des Epilepsiepatienten--Erscheinungsbild und Einflussgrössen.

Psychiatric disorders in epilepsy are frequently encountered. Contradictory reports are given in literature about the phenomenology of such disturbances and their relationship to seizure frequency. Depression has been described as mostly like "endogenous" with a family history of psychiatric illness or mostly "reactive". 32 patients with idiopathic Grand mal-seizures were studied using the Inpatient Multidimensional Psychiatric Scale (IMPS). They showed significant higher levels in scales of anxious depression and impaired functioning, no signs of hostility or delusion. Severity of depression was moderate compared with groups of inpatients suffering from endogenous and neurotic-depressive disorders. It was correlated with frequency of epileptic seizures and history of behaviour disturbances in infancy (Spearman-rang correlation).

Decreased serum tryptophan in patients with HIV-1 infection correlates with increased serum neopterin and with neurologic/psychiatric symptoms.

We investigated serum neopterin, tryptophan, and kynurenine concentrations in 23 HIV-1 seropositive patients (Walter Reed Stage 4-6). Ten patients presented with polyneuropathy and three with dementia, one of the patients with dementia also had polyneuropathy and dementia. We found significant associations between lower trytophan concentrations and neurologic/psychiatric symptoms. The negative correlation of tryptophan with kynurenine and neopterin concentrations indicates activity of indoleamine 2,3-dioxygenase (IDO) in patients. IDO can be induced by cytokines such as interferon-gamma and therefore low tryptophan levels may result from chronic immune stimulation in HIV-1 seropositives.

Clinical course of subacute HIV encephalitis.

A subacute encephalitis is increasingly recognized to be the most frequent cerebral manifestation of human immunodeficiency virus (HIV) infection. Contradictory reports are given in the literature concerning its clinical course. In the present study, a group of 19 patients with subacute encephalitis was followed for an average of 210 days. A steady progression of the disease was documented using the Karnofsky index. An advanced disease, rated according to the Walther Reed staging classification, but not isolated immunological parameters such as the ratio of OKT4/8 subsets are associated with more rapid progression of the encephalitis. Age, social status, duration of HIV positivity and antibody titers to cytomegalovirus could not be identified as contributing factors.

[Paranoid psychoses in HIV infection]. / Paranoide Psychosen bei HIV-Infektion.

Paranoid psychosis developed in two homosexual patients (aged 36 and 37 years) three and four years, respectively, after found to have an HIV infection. There was a marked reduction in the T-helper to T-suppressor-cell proportion (0.4 and 0.2). Neither computed tomography nor magnetic resonance imaging, nor microscopic, microbiological and biochemical tests of cerebrospinal fluid demonstrated opportunistic infection of the central nervous system. After treatment with haloperidol (3 mg daily) there was a rapid regression of the psychotic symptoms.

[Psychopathologic findings in AIDS in the early stage of the disease]. / Psychopathologische Befunde bei AIDS in frühem Krankheitsstadium.

After short review of literature about psychopathological findings in AIDS the history of three homosexual patients is reported. The clinical picture was characterised by complaints of restricted memory function and concentration increasing in the course of several months. In two patients a polyneuropathysyndrome could be found. CCT-examination showed no pathological findings. Even without other signs of AIDS manifestation psychoorganic symptoms of patients belonging to the known risk population should induce to further diagnostic confirmation of possible immunodeficiency.