- Email: [email protected]
ELECTROENCEPHALOGRAPHY AND HIV INFECTION
554 FINDINGS IN SEVEN HIV-INFECTED PATIENTS WITH FACIAL NERVE PALSY
abscess; 1 ischaemic lesion). In these cases EEG displayed focal or bilateral abnormalities well correlated with the topography of the lesion. 1 patient with a spinal tumour had a normal EEG. This study shows that an abnormal EEG does correlate with CNS dysfunction; that within group IV, EEG abnormalities correlate with the extent of brain dysfunction; and that patients with no neurological symptoms may sometimes have borderline EEG results, suggesting that a borderline EEG finding in a symptomless HIV-infected patient should prompt a prospective study. Moreover, lateralised or focal EEG changes may indicate a developing focal brain lesion and suggest the need for further
neurological exploration. *Without correspondmg tWith Kaposi sarcoma. ND = not done.
serum
bands.
and in whom there was no evidence of opportunistic central nervous system disease. All patients with facial nerve palsy had CSF abnormalities. Department of Neurology, Klinikum Grosshadern, University of Munich, D-8000 Munich 70, West Germany
EVA SCHIELKE H. WALTER PFISTER KARL M. EINHÄUPL
Neurological Institute, 40123 Bologna,
Italy
Department of Infectious Diseases, Ospedale Maggiore, Bologna
1.
FRANCESCO M. GRITTI
Enzensberger W, Fischer PA, Helm EB, Stille W. Value of electroencephalographym AIDS. Lancet 1985; i: 1047 A, Di Perri G, Strosselli M, Minoli L. HIV infection. Lancet 1987, ii. 1531.
2. Parisi
RR, Wnght DC, Tramont EC The Walter Reed staging classification for HTLV-III/LAV infection. N Engl J Med 1986, 314: 131-32 2. Luer W, Poser S, Weber T, et al. Chronic HIV encephalitis I: cerebrospinal fluid diagnosis. Klin Wochenschr 1988; 66: 21-28 3. Marshall DW, Brey RL, Cahill WT, Houk RW, Zahac RA, Boswell RN. Spectrum of cerebrospinal fluid findings in various stages of human immunodeficiency virus
PAOLO TINUPER PIERO DE CAROLIS MASSIMO GALEOTTI ANNA BALDRATI TOMMASO SACQUEGNA
Testing for neurological involvement in
1. Redfield
IDENTIFICATION OF EBV-DNA IN TUMOUR CELLS OF AIDS-RELATED LYMPHOMAS BY IN-SITU HYBRIDISATION
infection. Arch Neurol 1988; 45: 954-58
ELECTROENCEPHALOGRAPHY AND HIV INFECTION
SIR,-Electroencephalography (EEG) is a cheap and nonprocedure that can provide evidence of cerebral nervous (CNS) dysfunction. Lancet correspondents1.21,2 have suggested that EEG is useful in the early diagnosis of HIV encephalopathy but so far EEG abnormalities have not been correlated with the type of neurological lesion. We adopted a standard protocol to investigate 100 consecutive HIV-infected patients admitted to the department of infectious diseases, Ospedale Maggiore, Bologna, from March to December, 1988.3 patients had no symptoms of HIV infection, 8 had lymphadenopathy syndrome, 31 had AIDS-related complex, and 58 had AIDS. Every patient had a complete neurological examination and at least one EEG study; an abnormal EEG test was followed up by a computerised tomographic study of the brain and analysis of CSF. Neurologically the patients were divided into four groups. All EEG tracings were evaluated by the same technician, who was unaware of the clinical picture, and they were classed as normal, borderline (ie, with slight non-specific and non-lateralised abnormalities), or abnormal. The correlation between neurological invasive system
and EEG assessments is shown in the table. EEG abnormalities in group III (AIDS dementia) consisted of diffuse slow-wave activity with an anterior predominance. The clinical picture in group IV (secondary CNS involvement) requires more detailed analysis. 10 patients had diffuse brain involvement (1cerebral candidiasis, 6 meningitis, 2 metabolic encephalopathy, 1 cytomegalovirus encephalopathy) and in these cases EEG showed diffuse, polymorphic, slow-wave activities. 13 patients had focal cerebral lesions (11 toxoplasmosis, 7 lateralised and 4 bilateral; 1 frontal CORRELATION BETWEEN NEUROLOGICAL AND EEG FINDINGS
SIR,-HIV-infected individuals are at greatly increased risk of malignant lymphoma and the Centers for Disease Control (CDC) case definition has been revised to include this as a diagnostic criterion for AIDS.1 As of Dec 31, 1988, 358 AIDS patients had been registered in Denmark. Of these, 27 had lymphoma by this date, a cumulative rate of 75%. AIDS-related lymphomas have clinical and histopathological similarities with lymphomas in patients with other immunodeficiencies (both congenital and iatrogenic), leading to speculation that Epstein-Barr virus (EBV) may be implicated in their pathogenesis. In support of this, chromosomal translocations similar to those seen in Burkitt’s lymphoma have been described2 and in some cases EBV-associated nuclear antigen and EBV-genomes3 have been identified in tumour cells. In a review Emberg and Altiok’ identified 29 tumours that had been studied for EBV, 58% of which were positive for either EBV-antigens and/or EBV-genomes. In addition they described their fmdings in 25 AIDS-lymphomas, of which 7 were positive for EBV-DNA by Southern blotting. These studies have relied on filter-hybridisation techniques to demonstrate EBV genomes, and there have been no reports of the use of in-situ hybridisation to identify EBV in such neoplasms. This method is potentially more sensitive than Southern blotting (if only a small proportion of cells in the tissue contain the virus) and morphological features of the tissue are preserved, enabling the nature of the infected cell (ie, tumour cell or reactive lymphocyte) to be established. We have used in-situ hybridisation to investigate EBV-DNA in paraffin sections of 16 cases of lymphomas in Danish HIV-infected patients (including 3 surgical and 13 necropsy
specimens). 15 tumours were high grade non-Hodgkin’s lymphomas of B-cell type (centroblastic, immunoblastic, Burkitt’s, and lymphoblastic lymphomas according to the Kiel classification). One tumour was classified as Hodgkin’s disease. An EBV-specific Bani HI-W probe subcloned in plasmid pBR322 (provided by Dr H. Herbst, Berlin, courtesy of Dr G. W. Bomkamm, Freiburg, West Germany) was nick translated with 3sS-dCTP and used as described.s Probes for cytomegalovirus (courtesy of Dr B. Fleckenstein, Erlangen, West Germany) and for plasmid pBR322 without the EBV insert were used as negative controls. A clear positive autoradiographic signal for EBV was seen cell nuclei in 8 of the 16 cases tested, while 6 tumours negative for the virus (including the case of Hodgkin’s disease). In 2 of the cases non-specific signal prevented adequate assessment. There was no evidence that the presence or absence of EBV was over tumour were
abscess; 1 ischaemic lesion). In these cases EEG displayed focal or bilateral abnormalities well correlated with the topography of the lesion. 1 patient with a spinal tumour had a normal EEG. This study shows that an abnormal EEG does correlate with CNS dysfunction; that within group IV, EEG abnormalities correlate with the extent of brain dysfunction; and that patients with no neurological symptoms may sometimes have borderline EEG results, suggesting that a borderline EEG finding in a symptomless HIV-infected patient should prompt a prospective study. Moreover, lateralised or focal EEG changes may indicate a developing focal brain lesion and suggest the need for further
neurological exploration. *Without correspondmg tWith Kaposi sarcoma. ND = not done.
serum
bands.
and in whom there was no evidence of opportunistic central nervous system disease. All patients with facial nerve palsy had CSF abnormalities. Department of Neurology, Klinikum Grosshadern, University of Munich, D-8000 Munich 70, West Germany
EVA SCHIELKE H. WALTER PFISTER KARL M. EINHÄUPL
Neurological Institute, 40123 Bologna,
Italy
Department of Infectious Diseases, Ospedale Maggiore, Bologna
1.
FRANCESCO M. GRITTI
Enzensberger W, Fischer PA, Helm EB, Stille W. Value of electroencephalographym AIDS. Lancet 1985; i: 1047 A, Di Perri G, Strosselli M, Minoli L. HIV infection. Lancet 1987, ii. 1531.
2. Parisi
RR, Wnght DC, Tramont EC The Walter Reed staging classification for HTLV-III/LAV infection. N Engl J Med 1986, 314: 131-32 2. Luer W, Poser S, Weber T, et al. Chronic HIV encephalitis I: cerebrospinal fluid diagnosis. Klin Wochenschr 1988; 66: 21-28 3. Marshall DW, Brey RL, Cahill WT, Houk RW, Zahac RA, Boswell RN. Spectrum of cerebrospinal fluid findings in various stages of human immunodeficiency virus
PAOLO TINUPER PIERO DE CAROLIS MASSIMO GALEOTTI ANNA BALDRATI TOMMASO SACQUEGNA
Testing for neurological involvement in
1. Redfield
IDENTIFICATION OF EBV-DNA IN TUMOUR CELLS OF AIDS-RELATED LYMPHOMAS BY IN-SITU HYBRIDISATION
infection. Arch Neurol 1988; 45: 954-58
ELECTROENCEPHALOGRAPHY AND HIV INFECTION
SIR,-Electroencephalography (EEG) is a cheap and nonprocedure that can provide evidence of cerebral nervous (CNS) dysfunction. Lancet correspondents1.21,2 have suggested that EEG is useful in the early diagnosis of HIV encephalopathy but so far EEG abnormalities have not been correlated with the type of neurological lesion. We adopted a standard protocol to investigate 100 consecutive HIV-infected patients admitted to the department of infectious diseases, Ospedale Maggiore, Bologna, from March to December, 1988.3 patients had no symptoms of HIV infection, 8 had lymphadenopathy syndrome, 31 had AIDS-related complex, and 58 had AIDS. Every patient had a complete neurological examination and at least one EEG study; an abnormal EEG test was followed up by a computerised tomographic study of the brain and analysis of CSF. Neurologically the patients were divided into four groups. All EEG tracings were evaluated by the same technician, who was unaware of the clinical picture, and they were classed as normal, borderline (ie, with slight non-specific and non-lateralised abnormalities), or abnormal. The correlation between neurological invasive system
and EEG assessments is shown in the table. EEG abnormalities in group III (AIDS dementia) consisted of diffuse slow-wave activity with an anterior predominance. The clinical picture in group IV (secondary CNS involvement) requires more detailed analysis. 10 patients had diffuse brain involvement (1cerebral candidiasis, 6 meningitis, 2 metabolic encephalopathy, 1 cytomegalovirus encephalopathy) and in these cases EEG showed diffuse, polymorphic, slow-wave activities. 13 patients had focal cerebral lesions (11 toxoplasmosis, 7 lateralised and 4 bilateral; 1 frontal CORRELATION BETWEEN NEUROLOGICAL AND EEG FINDINGS
SIR,-HIV-infected individuals are at greatly increased risk of malignant lymphoma and the Centers for Disease Control (CDC) case definition has been revised to include this as a diagnostic criterion for AIDS.1 As of Dec 31, 1988, 358 AIDS patients had been registered in Denmark. Of these, 27 had lymphoma by this date, a cumulative rate of 75%. AIDS-related lymphomas have clinical and histopathological similarities with lymphomas in patients with other immunodeficiencies (both congenital and iatrogenic), leading to speculation that Epstein-Barr virus (EBV) may be implicated in their pathogenesis. In support of this, chromosomal translocations similar to those seen in Burkitt’s lymphoma have been described2 and in some cases EBV-associated nuclear antigen and EBV-genomes3 have been identified in tumour cells. In a review Emberg and Altiok’ identified 29 tumours that had been studied for EBV, 58% of which were positive for either EBV-antigens and/or EBV-genomes. In addition they described their fmdings in 25 AIDS-lymphomas, of which 7 were positive for EBV-DNA by Southern blotting. These studies have relied on filter-hybridisation techniques to demonstrate EBV genomes, and there have been no reports of the use of in-situ hybridisation to identify EBV in such neoplasms. This method is potentially more sensitive than Southern blotting (if only a small proportion of cells in the tissue contain the virus) and morphological features of the tissue are preserved, enabling the nature of the infected cell (ie, tumour cell or reactive lymphocyte) to be established. We have used in-situ hybridisation to investigate EBV-DNA in paraffin sections of 16 cases of lymphomas in Danish HIV-infected patients (including 3 surgical and 13 necropsy
specimens). 15 tumours were high grade non-Hodgkin’s lymphomas of B-cell type (centroblastic, immunoblastic, Burkitt’s, and lymphoblastic lymphomas according to the Kiel classification). One tumour was classified as Hodgkin’s disease. An EBV-specific Bani HI-W probe subcloned in plasmid pBR322 (provided by Dr H. Herbst, Berlin, courtesy of Dr G. W. Bomkamm, Freiburg, West Germany) was nick translated with 3sS-dCTP and used as described.s Probes for cytomegalovirus (courtesy of Dr B. Fleckenstein, Erlangen, West Germany) and for plasmid pBR322 without the EBV insert were used as negative controls. A clear positive autoradiographic signal for EBV was seen cell nuclei in 8 of the 16 cases tested, while 6 tumours negative for the virus (including the case of Hodgkin’s disease). In 2 of the cases non-specific signal prevented adequate assessment. There was no evidence that the presence or absence of EBV was over tumour were