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Tamoxifen is an antioestrogen widely used in the breast cancer treatment. Its paradoxical antioestrogenic action on breast and its oestrogenic action on the endometer is well-known. Since 1988, few cases of malignant mixed müllerian tumors following tamoxifen were described. We report a new case of uterine malignant mixed müllerian tumor four years after the end of tamoxifen for breast cancer.

Intracranial neurenteric cysts are rare entities. The term is currently used to describe epithelial cysts that are lined with a presumed endodermal-derived epithelium and are mostly located in the posterior fossa. Preoperative diagnosis is often difficult because of their clinical presentation, which may resemble a subarachnoid hemorrhage, and the radiological aspect, which can mimic vascular pathologies. We describe a posterior fossa neurenteric cyst in a 27-year-old woman, who presented with sudden headache as the only symptom and who was addressed to our hospital for subarachnoid hemorrhage. Diagnostic angiography was negative and MRI revealed a prepontine cystic lesion. The patient underwent a posterolateral approach on the right side, with subtotal resection of the lesion. We discuss the embryologic, diagnostic and therapeutic aspects of these cysts and review the literature.

Hashimoto's encephalopathy (HE) is a rare neurological complication of chronic lymphocytic thyroiditis. As its clinical presentation is aspecific, other etiologies of acute encephalopathy have to be ruled out. We report the case of a 29-year old woman with neuropsychiatric signs preceding coma, myoclonus and epileptic seizures. Clinical and electroencephalographic features were consistent with the diagnosis of new variant of Creutzfeldt-Jakob disease. However, high titres of antithyroid antibodies in serum directed towards the diagnosis of HE. Despite oral steroids, the patient died five months later. Neuropathological findings ruled out spongiform encephalopathy and disclosed aspecific activated microglia. Our observation suggests that this process could be involved in the pathogenesis of HE. Even in the absence of clinical dysthyroidism, HE diagnosis has to be suspected in the settings of acute encephalopathy associated with seric antithyroid antibodies.

Cerebral amyloid angiopathies are defined by the presence of amyloid substance in the walls of cerebral vessels. All amyloid substances have a particular physico-chemical structure, which imparts certain specific staining properties, but the biochemical composition of different amyloid types varies. Different forms of cerebral amyloid angiopathy have been identified, based on the biochemical nature of the protein deposited (e.g. beta-amyloid, cystatin C, transthyretin, gelsolin, amyloid protein Bri, prion protein). Some cerebral amyloid angiopathies are familial; these prompted genetic studies which in turn led to a better understanding of the genes coding for different amyloid proteins. As a group, cerebral amyloid angiopathies have certain neuropathological lesions in common. Infiltration by amyloid substance results in weakening of the small vessel walls and secondary complications responsible for changes such as microinfarcts and miliary haemorrhages in the cerebral cortex, lobar haemorrhages and/or leucoencephalopathy. These changes form the basis of the neurological complications: meningeal and cerebral haemorrhages, transient ischaemic episodes, vascular dementia. However each type of hereditary cerebral amyloid angiopathy has individual clinical and histopathological features reflecting the severity of arterial involvement, the extent of amyloid deposition within or outside the central nervous system, and the association with other neurodegenarative changes.

This paper reports the clinico-pathological data in a French family with orthochromatic leukodystrophy. The parents were first cousins and had seven children. Among those, two sisters and one brother presented with neurological signs, with onset around the 5(th) decade, including a dementing syndrome of frontal type, a tetrapyramidal syndrome, seizures, and, in one sibling, a cerebellar syndrome. CT scan or MRI showed diffuse involvement of the white matter. The neurological signs worsened progressively leading to death within 11 and 22 months. Neuropathological examination was performed in two cases. It revealed characteristic orthochromatic leukodystrophy. In one case, the presence of pigmented macrophages and astrocytes was suggestive of Van Bogaert and Nyssen disease. However there were some atypical features including the absence of pigmented cells in the second case whose clinical course was shorter, and the cavitary appearance of the white matter changes with a relative increase in the number of oligodendrocytes raising the issue of a possible link between this condition and cavitary orthochromatic leukodystrophies.

We present the neuroimaging features with clinical and pathologic correlation in a case of Progressive Multifocal Leukoencephalopathy (PML) in AIDS. CT and MRI showed typical lesions of PML. At pathology examination, characteristic lesions of PML were found in association with HIV encephalitis due to CNS infection by the virus.

Since its description in 1986, Fatal Familial Insomnia (FFI) became the third most common inherited prion diseases (23 described families, 3 isolated cases). It is characterized by a mutation at codon 178 of the prion protein gene cosegregating with the methionine polymorphism at codon 129 of the mutated allele. Insomnia, dysautonomia, disruption of circadian rhythms and motor dysfunctions (myoclonus, ataxia, dysarthria, spasticity) are the main clinical symptoms in the homozygote patients (met/met at codon 129). Heterozygotes have motor dysfunctions from onset and cognitive changes. Pheno-typic variability does not appear to be strictly related to codon 129 polymorphism as recently stressed in some reports. Neuropathology shows marked neuronal loss and gliosis in the thalamus, especially in the medio-dorsal and antero-ventral nuclei, without any amyloïd deposits. Some spongiosis may be seen essentially in the cerebral cortex, in patients with longer duration disease. The D178N mutation coupled with the 129 valine codon is linked to a subtype of Creutzfeldt-Jakob disease. However, in these two phenotypically different diseases, two protease resistant fragments of the pathogenic PrP (PrPres) are accumulated. They differ in molecular mass. In FFI PrPres, the unglycosylated form is underrepresented. This particularity does not result from the preferential conversion of the glycosylated forms but from an inaccessibility of non glycosylated form to conversion. PrPres has been shown to be form allelic origin. Neuronal apoptosis was found to contribute to neuronal loss in FFI. Its presence correlates with neuronal loss, being invariably noticed in the thalamus and medullary nuclei. It is not correlated with PrPres accumulation. The quantity of deposits is globally low in FFI brains and rarely immunohistochemically detected. Pathogenesis of lesions and clinical signs remain to be assessed. Protein dysfunction could be hypothesized according to some clinical and experimental data as well as to the discordance between protein accumulation and programmed cell death. Neurotoxicity is also postulated. Studies on this pathology led to consider the existence of "strains" in human prion diseases. Despite remarkable advances, many issues remain unsolved in this non spongiform prion disease.

Neuronal loss is a salient feature of prion diseases; however, its causes and mechanisms are unclear. The possibility that it could occur through an apoptotic process has been postulated and this is consistent with the lack of inflammation in prion disorders as supported by experimental studies. In order to test this hypothesis in humans, we examined samples of frontal and temporal cerebral cortex, striatum, thalamus and cerebellum from 26 patients who died from prion diseases. They included 16 cases of Creutzfeldt-Jakob disease (5 sporadic cases, 5 familial, 3 iatrogenic, and 3 cases with the new variant), and 10 cases of fatal familial insomnia including 8 homozygotes methionine/methionone at codon 129 of the prion protein gene and 2 heterozygotes. These were compared with age and sex matched controls. Using in situ end labelling, we identified apoptotic neurons in all the cases of Creutzfeldt-Jakob disease. A single labelled neuron was found in the eldest control. Apoptotic neurons were mostly found in damaged regions and their presence and abundance seemed to correlate closely with neuronal loss. This supports the view that apoptosis of neurons is a feature of prion diseases and may contribute to the neuronal loss which is one of the main characteristics of these conditions. Neuronal apoptosis also correlated well with microglial activation as demonstrated by the expression of major histocompatibility complex class II antigens and axonal damage as identified by beta-amyloid protein precursor immunostaining. In contrast, we found no obvious relationship between the topography and severity of neuronal apoptosis and the type, topography and abundance of prion protein deposits as demonstrated by immunohistochemistry.

HIV-associated neurological manifestations: dementia, myelopathy, and neuropathy, have become one of the commonest causes of neurological disorders in young people. Cognitive impairment develops in about 30 p. 100 of patients with AIDS and frank dementia in 15 to 20 p. 100 with an annual incidence after AIDS of approximatively 7 p. 100. Typically, the onset of dementia is relatively abrupt over a few weeks or months. The clinical manifestations of the encephalopathy now termed "HIV-dementia", suggest predominant subcortical or frontal involvement. Typical presentation includes apathy and inertia, memory loss and cognitive slowing, minor depressive symptoms and withdrawal from usual activities. Neurological examination may show hypertonia of lower limbs, tremor, clonus, frontal release signs and hyperactive reflexes. Terminally, the patient is bedbound, incontinent, abulic or mute with decorticate posturing leading to death over 3 to 6 months. However, a stabilisation and even a regression of the cognitive disorders have been observed following antiretroviral treatment. Radiological features of HIV dementia include both central and cortical atrophy and white matter rarefaction. However they are neither invariable nor specific. Together with CSF examination, they are more important to exclude opportunistic infections. Indeed, although a completely normal CSF profile may reasonably exclude the diagnosis; at present, no single test or combination of tests can reliably diagnose HIV dementia. Although the clinical characteristics of HIV-dementia are now clearly established, its pathogenesis is unclear and its pathological counterpart remains a matter of debate. A number of "HIV-induced" lesions may be found in the brain of AIDS patients and their causative role in HIV-dementia has been considered. They include HIV encephalitis due to productive CNS infection by the virus, diffuse white matter pallor "HIV-leukoencephalopathy" reflecting an abnormality of the blood brain barrier, involvement of the grey matter, "diffuse poliodystrophy", with neuronal loss that results, at least partly, from a process of programmed cell death and axonal damage. These changes are variably associated in patients with HIV dementia, however none of them can be closely related to the cognitive disorders. This suggests that the neuronal dysfunction underlying HIV-dementia results from different mechanisms that are variably associated and may interact mutually. These include production of viral proteins, microglial activation with consequent production of neurotoxic factors such as proinflammatory cytokines, free radicals, derivates of arachidonic acid, or quinoleic acid, and blood borne neurotoxic factors in particular cytokines.

Early HIV-1 invasion of the central nervous system has been demonstrated by many cerebrospinal fluid studies; however, most HIV-1 carriers remains neurologically unimpaired during the so called "asymptomatic" period lasting from seroconversion to symptomatic AIDS. Therefore, there are very few neuropathological studies in the early pre-AIDS stages and the natural history of central nervous system changes in HIV-1 infection remains poorly understood. Examination of brains of asymptomatic HIV-1 positive individuals who died accidentally and of rare cases with acute fatal encephalopathy revealing HIV infection, and comparison with experimental simian immunodeficiency virus and feline immunodeficiency virus infections suggest that invasion of the CNS by HIV-1 occurs at the time of primary infection and induces an immunological process in the central nervous system. This includes an inflammatory T-cell reaction with vasculitis and leptomeningitis, and immune activation of brain parenchyma with increased number of microglial cells, upregulation of major histocompatibility complex class II antigens and local production of cytokines. Myelin pallor and gliosis of the white matter are usually found are likely to be the consequence of opening of the blood brain barrier due to vasculitis; direct damage to oligodendrocytes by cytokines may also interfere. These white matter changes may explain, at least partly, the early cerebral atrophy observed, by magnetic resonance imaging, in asymptomatic HIV-1 carriers. In contrast, cortical damage seems to be a late event in the course of HIV-1 infection. There is no significant neuronal loss at the early stages of the disease, no accompanying increase in glial fibrillary acid protein staining in the cortex, and only exceptional neuronal apoptosis. Although HIV-1 proviral DNA may be demonstrated in a number of brains, viral replication remains very low during the asymptomatic stage of HIV-1 infection. This makes it likely that, although opening of the blood brain barrier may facilitate viral entry into the brain, specific immune responses including both neutralising antibodies and cytotoxic T-lymphocytes, continuously inhibits viral replication at that stage.

Early HIV-1 invasion of the central nervous system has been demonstrated by many cerebrospinal fluid studies; however, most HIV-1 carriers remain neurologically unimpaired during the so-called "asymptomatic" period lasting from seroconversion to symptomatic AIDS. Therefore, very few neuropathological studies have been conducted in the early pre-AIDS stages, and the natural history of central nervous system changes in HIV-1 infection remains poorly understood. Examination of brains of asymptomatic HIV-1 positive individuals who died accidentally and of rare cases with acute fatal encephalopathy revealing HIV infection, and comparison with experimental simian immunodeficiency virus and feline immunodeficiency virus infections suggest that, invasion of the CNS by HIV-1 occurs at the time of primary infection and induces an immunological process in the central nervous system. This includes an inflammatory T-cell reaction with vasculitis and leptomeningitis, and immune activation of brain parenchyma with increased number of microglial cells, upregulation of major histocompatibility complex class II antigens and local production of cytokines. Myelin pallor and gliosis of the white matter are usually found and are likely to be the consequence of opening of the blood-brain barrier due to vasculitis; direct damage to oligodendrocytes by cytokines may also be involved. These white matter changes may explain, at least partly, the early cerebral atrophy observed, by magnetic resonance imaging, in asymptomatic HIV-1 carriers. In contrast, cortical damage seems to be a late event in the course of HIV-1 infection. There is no significant neuronal loss at the early stages of the disease, no accompanying increase in glial fibrillary acid protein staining in the cortex, and only exceptional neuronal apoptosis. Although HIV-1 proviral DNA may be demonstrated in a number of brains, viral replication remains very low during the asymptomatic stage of HIV-1 infection. This makes it likely that, although opening of the blood brain barrier may facilitate viral entry into the brain, specific immune responses including both neutralising antibodies and cytotoxic T-lymphocytes, continuously inhibit viral replication at this stage.

Progressive multifocal leukoencephalopathy is a subacute demyelinating disease of the central nervous system due to an opportunistic infection by a polyomavirus, most often JC virus, which predominantly infects oligodendrocytes. Progressive multifocal leukoencephalopathy used to be a rare condition, usually complicating lymphoproliferative diseases. Since the onset of the AIDS epidemic, its incidence has considerably increased and HIV infection has become, by far, the main risk factor for the disease. In AIDS patients, progressive leukoencephalopathy frequently shows atypical clinical and pathological features. The development of malignant glial tumors, within demyelinating regions, in patients with progressive multifocal leukoencephalopathy, has been reported in exceptional cases. The course of progressive multifocal leukoencephalopathy is invariably fatal. The diagnosis can only be made with certainty by histopathological examination of the brain, on cerebral biopsy or at postmortem. However, neuroradiological features may be extremely suggestive in many cases and PCR seems to be a reliable technique for demonstrating viral genome in the CSF. A few antiviral treatments have been proposed, however their efficacy is difficult to assess due to the low prevalence of the disease and the occurrence of rare cases with spontaneously prolonged survival.

Presence of human herpes virus type 8 (HHV8), detected by nested PCR, and expression of Epstein-Barr virus (EBV), as assessed by immunochemistry and in situ hybridization, were evaluated in 20 primary non-Hodgkin immunoblastic lymphomas (NHL) of the central nervous system (CNS) from patients who died from AIDS, and in 10 samples of cerebral tissues from patients who died from AIDS, without cerebral lymphoma or Kaposi's sarcoma, as controls. Six lymphomas (30%) contained HHV8 sequences, and 19 (95%) expressed EBV; detection of HHV8 was more frequent in patients with Kaposi's sarcoma, than in other subjects (4/6 versus 2/14). Three (30%) controls contained HHV8 sequences, whereas none expressed EBV. AIDS-related CNS NHL is therefore clearly associated with EBV expression, while the presence of HHV8 appears occasional, probably associated with a low tissue viral load. The high frequency of HHV8 in AIDS-related primary CNS NHL patients with Kaposi's sarcoma suggests that this virus could play a role in the pathogenesis of some cerebral lymphomas.

Fungal infections of the central nervous system are uncommon in human immunodeficiency virus infected patients. The most frequently encountered is cerebromeningeal cryptococcosis. We report 3 clinicopathological cases of rarer fungal infections of the central nervous system in AIDS patients due to Candida and Aspergillus genders. In most cases, a systemic candida infection or aspergillus pulmonary infection preceded the onset of cerebral granulomas or abscesses. These infections usually occurred at the terminal stage of the disease and were associated with other neuropathologies. Neutropenia associated with lymphopenia represents a frequent risk factor along with intravenous catheter.

Infections of the central nervous system by Herpes simplex viruses (Herpes simplex type 1 and Herpes simplex type 2) are uncommon in acquired immune deficiency syndrome and are often clinically and pathologically atypical. We have collected 11 cases of herpes simplex encephalomyelitis in AIDS patients reported in the literature. Only 3 of these cases presented with a typical, necrotizing, limbic encephalitis. Other clinicopathological patterns included ventriculitis, rhombencephalitis and myelitis. Ventriculitis and rhombencephalitis were usually due to infection by HSV-1, whereas myelitis was mostly due to HSV-2 infection. Distinction between the 2 types of virus is often difficult by immunohistochemistry due to frequent cross reactivity and usually requires tissue culture, in situ hybridization, or polymerase chain reaction. Association of HSV encephalomyelitis with productive infection of the central nervous system by the human immunodeficiency virus was only found in one case. In contrast, co-infection with cytomegalovirus was found in 9 of the 11 cases. One case also had had varicella zoster virus vasculitis, and another case also had a cerebral malignant non Hodgkin's lymphoma in which Epstein Barr virus genome was identified. This supports the view that concomitant herpes-virus infections of the central nervous system is a characteristic feature of AIDS.

We have reviewed 23 cases of varicella-zoster virus infection of the central nervous system in patients with the acquired immunodeficiency syndrome, previously reported in the literature, including 11 from our own series. This allowed us to identify 5 clinico-pathological patterns which could occur simultaneously. In most cases, viral proteins or viral genome were identified using immunocytochemistry or in situ hybridization. Multifocal encephalitis involves predominantly the white matter and is likely to be due to haematogenous spread of the infection. Ventriculitis may have variable appearance according to the course of the disease. In one incipient case, the ependymal lining appeared irregular with foci of infected ependymal cells some of which protruded into the ventricular lumen; in other instances, there was acute or chronic necrosis of the ventricular wall with marked vasculitis. Acute haemorrhagic meningo-myelo-radiculitis with necrotising vasculitis may be associated with ventriculitis and results from shedding of infected ependymal cells into the ventricular lumen and secondary seeding of the cerebrospinal fluid. Focal necrotising encephalitis or myelitis usually follows cutaneous herpes zoster in the corresponding dermatoma and is considered to result from neural spread from the diseased trigeminal or dorsal root ganglion. Vasculopathy involving leptomeningeal arteries and causing cerebral infarcts is associated with meningitis in most cases. These findings are in keeping with the observation in other immunocompromised patients, that varicella-zoster virus spread to the central nervous system may follow different routes. Our study tends to show that varicella-zoster virus infection of the central nervous system is more frequent in the acquired immunodeficiency syndrome than previously suspected and suggests this diagnosis must be considered systematically in cases of encephalitis, ventriculitis, focal myelitis, acute myeloradiculitis and cerebral infarcts in these patients, since an efficient treatment is available.

Apart from the unique changes characteristic of "HIV encephalitis", the productive infection of central nervous system by HIV, which involves predominantly the white matter and basal ganglia, evidence is accumulating that the cerebral cortex may also be affected in AIDS patients. Neuronal loss, suspected at microscopical examination, has been demonstrated by a number of morphometric studies. However, the cause and mechanism of neuronal damage in HIV infection, are still unclear. In an attempt to look for an apoptotic process at the origin of neuronal loss in AIDS, we examined samples of frontal cortex, temporal cortex and basal ganglia from 12 patients who died from AIDS and 4 HIV-positive asymptomatic cases using in situ end labelling to demonstrate characteristic DNA fragmentation. These were compared with 5 seronegative asymptomatic controls, and 2 seronegative patients with Alzheimer's disease. We demonstrated neuronal apoptosis in all the AIDS cases and in the Alzheimer's cases. Positive in situ end labelling was usually associated with morphological changes suggestive of neuronal apoptosis. Semiquantitative appreciation of the density of apoptotic neurons showed that neuronal apoptosis was more severe in atrophic brains. In contrast, no correlation was found between the density of apoptotic neurons and the presence of HIV encephalitis or a history of cognitive disorder. Only occasional apoptotic neurons were found in one asymptomatic, HIV-positive case. Apoptosis was never observed in asymptomatic seronegative cases. Experimental studies tend to support our in vivo findings. Infection by HIV of primary cultures of human embryonic central nervous system induced frequent apoptosis of neurons. No apoptotic cell was identified in non infected control cultures.

Cerebral infarcts complicating heroin abuse have been seldom reported and only clinically and radiologically documented. We report a pathological case of cerebral infarct in a heroin sniffer. A 31 year old, male, heroin sniffing addict for several years, with no known past neurological history, was found dead one morning. The evening before, he had presented the usual signs of recent heroin intake. Opiates were found in large amounts in blood and urine. Post mortem HIV serology was negative. Post mortem examination revealed the usual signs of heroin addiction, but no cutaneous signs of IV drug use. Myocardial ischemic lesions of various ages involved the anterolateral part of the left ventricle; coronary arteries were normal. Neuropathological study revealed, partly cystic infarcts involving both cerebral hemispheres. They were mostly cortical with an intralaminar pattern and a watershed distribution at the boundaries between the territories of the anterior and middle cerebral arteries and the middle posterior cerebral arteries. Intracerebral vessels, large intracranial and cervical arteries were normal.

In order to evaluate the diagnostic and prognostic value of MRI in the very early stages of HIV infection, we have compared the results of postmortem brain MRI and neuropathological studies in 7 asymptomatic HIV seropositive individuals, 8 seronegative controls with similar cause of death and 6 patients who died of AIDS in the absence of focal cerebral changes (opportunistic infection or tumour). Cerebral atrophy was consistently evaluated by both techniques. Seropositive asymptomatic cases were significantly more atrophic than the seronegative controls and significantly less atrophic than AIDS patients. Small high signal intensity areas in the white matter and basal ganglia were not significantly more frequent in seropositives than in seronegatives. No corresponding lesion was found at neuropathological examination. Diffuse myelin pallor of the cerebral white matter on myelin preparation was somewhat more severe in seropositive asymptomatic cases than in seronegative controls and less than in AIDS cases. However, these differences were not statistically significant. No significant correlation could be found between neuropathological myelin pallor and diffuse signal abnormalities of the white matter on MRI. We conclude that brain abnormalities are present at the early asymptomatic stage of HIV infection. These include vasculitis with opening of the blood brain barrier and consequent myelin pallor and gliosis of the white matter, and moderate brain atrophy. However MRI correlates are discrete or non specific on post mortem examination, and some probably correspond to scars of transient vascular inflammation. It is very unlikely that MRI examination has any diagnostic or prognostic value at the early stages of the disease.

Eighty patients were followed up prospectively. Histological correlation was obtained in 25 cases. All MRI examinations were performed on at 0.5 Tesla in T1-weighted sequences with and without gadolinium injection, and in axial or frontal T2-weighted spin echo sequences. Histological confirmation was obtained 30 days on average after the last MRI examination. Immunohistochemical stainings were performed in search of CMV, VZV, toxoplasma, HIV antigen and lymphoma.CMV meningoencephalitis was found in 6 cases. In 3 of these it was manifested by atrophy, either isolated or associated with high signal intensity punctiform areas. Histology detected cortical or subcortical microglial nodules. In 2 cases MRI displayed abnormalities of subependymal nodular signals without enhancement, associated with punctiform abnormalities of subcortical signals. Histology showed subependymal foci of necrosis and abnormalities of white matter. In one case, MRI showed a ventriculitis confirmed by histology. VZV meningoencephalitis was diagnosed in 2 cases. MRI displayed abnormal basal ganglia related to meningitis (n = 1). All abnormalities were confirmed at histology.Some images (ventriculitis, infarction in basal ganglia, abnormal subependymal signal) would suggest VZV and CMV encephalitis. Other images (abnormalities of punctiform signals or atrophy) are not specific.

The authors present the different aspects of HIV encephalitis in CT and MR in a series of 15 patients with anatomopathological proof. Atrophy was the most commonly found lesion (12 patients) and could rapidly be evolutive. White matter lesions (9 patients) were more of ten nodular than diffuse. They were better demonstrated by MRI and did not enhance after intra-venous injection of DOTA-gadolinium. A frequent association with opportunistic infections (toxoplasmosis: 10 patients, CMV:2 patients), lymphoma (4 patients), or PML (3 patients) was observed which emphasized the low specificity of brain imaging in patients with HIV encephalitis.

A 36 years-old male with AIDS, presented with left hemiparesis revealing a right parietal tumour. Stereotactic biopsy demonstrated a malignant non-Hodgkin's lymphoma. His condition partially improved following radiotherapy and chemotherapy. Three months later he was re-admitted with progressive bilateral root pain and urinary incontinence resulting in paraplegia with sensory loss below T10. He died one month later from generalized sepsis. Neuropathology confirmed an immunoblastic B-cell malignant non-Hodgkin's lymphoma in the white matter of the right parietal lobe and revealed a centrospinal localisation of the lymphoma in the thoracic cord at T10. There was no visceral localisation of the tumour. Secondary spread to the spinal cord of malignant non Hodgkin's lymphomas, usually causes meningo-myelo-radiculitis. Intraspinal deposits of primary cerebral lymphomas are uncommon and have never been previously described in AIDS, to our knowledge. Their pathogenesis is unclear. In our case, neuropathological findings are consistent with diffusion of the primary tumour to leptomeninges and secondary infiltration of the spinal cord along the perivascular spaces.

We report two cases of multiple sclerosis with concentric patterns of demyelinated foci on MR images. These were compared with the pathological data of Balò's disease. The T2-weighted MR images displayed alternating high and low signal areas which probably corresponded to the concentric type of demyelination. Our two cases were characterized by their acute onset and their regression following corticosteroid therapy. This suggests that Balò's disease may be a transient disease and not always associated with a fatal course.

A cohort of 50 initially asymptomatic seropositive patients have been followed for five years. Various clinical evolution have been observed: 21 remain stable, 29 underwent complications that take then to AIDS, 11 died. In any case, invariability of the MRI anomalies seems had to be imputed to primary infection scars.

A variety of the central nervous system lesions may cause a diffuse encephalopathy in AIDS patients. Apart from viral encephalitides already described in part one, metabolic encephalopathies are a classical cause of diffuse brain dysfunction and are frequent at the terminal stage of the disease. Atypical forms of some infectious, vascular or tumoural processes which usually determine focal lesions, may cause diffuse encephalopathies. These forms are not exceptional in AIDS. The association in the same patient of lesions due to different agents is the rule. Whereas most of the neurological complications of AIDS occur late in the course of the disease, symptomatic, usually transient encephalopathies have been described in the early stages of HIV infection in rare cases. The authors conclude by proposing a management plan, since therapeutic advances have raised some hopes of improvement and even regression of some of these disorders in a few cases, so that physicians do not systematically give up when an AIDS patient presents with a diffuse encephalopathy.

The diagnostic approach of focal central nervous system lesions in AIDS patients is now well established. In contrast, it is extremely difficult to determine the cause of diffuse encephalopathies, occurring frequently at the terminal stage of AIDS. Imaging is usually non specific and laboratory investigations are seldom contributive. In most cases, the aetiological diagnosis is provided by post mortem examination. In this first part of the study the authors deal with viral encephalitides which represent a classical and frequent cause of diffuse encephalopathy in AIDS. HIV encephalitis usually causes a progressive brain disease resulting in severe dementia; imaging may show diffuse leucoencephalopathy and/or cortico-subcortical atrophy. CMV encephalitis is often asymptomatic, discovered at autopsy; however, this diagnosis should be considered in patients with an encephalopathy of rapid onset, discrete signs of meningitis, symptoms of myelo-radiculitis, or a systemic CMV infection. Varicella-zoster virus encephalitis is not uncommon and may occur in the absence of characteristic rash. Infections by herpes simplex and measles viruses are exceptional.

A 78 year-old male presented with a bilateral pyramidal syndrome, urinary incontinence and mild intellectual slowing. He died seven months after onset of the neurological signs from cerebral infarct and heart failure. Neuropathological examination showed predominant involvement of the cerebral white matter including diffuse myelin pallor, astrocytic gliosis and small necrotic foci. Polyglucosan bodies were diffuse in the cerebral cortex, white matter, brainstem, cerebellum and proximal part of the cranial nerves. In these latter, some polyglucosan bodies were found within myelinated axons but the inclusions mostly involved astrocytic processes. This case is characteristic of the polyglucosan body disease. It is compared with the autopsy and biopsy cases previously reported in the literature.

A 41-year-old male homosexual with AIDS was hospitalized for temperature elevation to 40 degrees C with confusion. Neurologic evaluation found psychomotor slowing and temporospatial disorientation with no focal signs. The CD4 count was 100/mm3. CSF analysis and the CT scan were normal. Despite antiviral treatment the patient died fifteen days after admission. Gross appearance of the brain was normal. Histologic examination disclosed multiple, small foci of demyelination characteristic of progressive multifocal leukoencephalopathy. These foci were disseminated among the U fibers. In situ hybridization and immunocytochemical studies demonstrated papovavirus particles in oligodendrocytes and a few astrocytes. This case shows that papovavirus infection in AIDS patients may be responsible for a diffuse febrile encephalopathy with normal CT scan findings and a rapidly progressive course.

Gerstmann-Sträussler-Scheinker's disease is a familial spongiform encephalopathy whose pathological hallmark is the existence--especially in the cerebellum--of numerous amyloid plaques. We report here the third clinicopathological case in a French family. Brain tissue from one of its members--initially described as familial Creutzfeldt-Jakob's disease--has been reported as successfully inoculated to monkeys. We present the currently accumulating data favouring the hypothesis of a common etiology for familial Creutzfeldt-Jakob's disease and Gerstmann-Sträussler-Scheinker's disease. The familial characteristics, resulting in different durations of incubation and evolution, could lead to different clinical and histological expressions.

The central nervous system was examined in 135 adult AIDS patients who died between August 1982 and December 1990. Twenty two brains showed non-diagnostic changes including microglial nodules, discrete myelin pallor with reactive astrocytosis, mineralization of blood vessels and granular ependymitis. In 105 brains with specific changes, toxoplasmosis was the most frequent finding (55 cases) manifested by multifocal necrotic lesions or diffuse pseudo-encephalitic process. Other opportunists included cytomegalovirus (21 case), progressive multifocal leukoencephalopathy (1 cases), cryptococcosis (6 cases), mycobacterium avium intracellulaire (2 cases), varicella-zoster virus (2 cases), aspergillosis (1 case) and multiple bacterial microabscesses (1 case). Multinucleated giant cells were found in 52 cases. In 40 cases, they were widely disseminated throughout the brain and in 39 cases, they were associated with diffuse or multifocal white matter changes. Fifteen cases had a cerebral lymphoma, 9 hepatic encephalopathy, 1 centropontine myelinolysis and 1 focal pontine leukoencephalopathy. Three cases had a cerebral haemorrhage due to disseminated intravascular coagulation, antithrombin therapy and amyloid angiopathy. Spinal changes in 13 cases included vacuolar myelopathy (7 cases), HIV myelitis (1 case) and ganglio-radiculitis (1 cases), cytomegalovirus myelo-radiculitis (1 case) secondary spread from a lymphoma (1 case) and spinal infarcts due to disseminated intravascular coagulation (1 case). These lesions were frequently atypical and various combinations of all these pathologies were encountered in the same brain, sometimes in the same area and occasionally in the same cell. Chronological variations in the incidence of some complications could be related to changes in treatment.

Spinal cord lesions, although far less frequent than brain lesions, are not uncommon in AIDS. Almost all diffuse or multifocal pathological processes involving the central nervous system and/or leptomeninges may also affect the spinal cord. However, some of them involve it predominantly causing specific, clinically overt, myelopathic diseases. The most characteristic of these is vacuolar myelopathy which usually manifests as progressive spastic ataxia. Its incidence varies in different pathological series and its pathogenesis is still controversial. Acute meningomyeloradiculitis in AIDS patients presents a remarkably uniform and distinct clinical and cerebrospinal fluid profile although they might be due to various causes including cytomegalovirus infection, syphilis, mycobacterial infection or leptomeningeal malignancy. Tumoral focal syndromes have exceptionally been recorded due to epidural lymphomas, intraspinal gliomas or toxoplasma abscesses. Spinal cord ischemic lesions have been documented in two cases: they were related to inflammatory lesions of the blood vessels in one case and to diffuse intravascular coagulation in the other. An ascending myelitis syndrome, secondary to spinal cord infection by both herpes simplex virus type 2 and cytomegalovirus, without significant vasculitis has also been reported.

A case of progressive supranuclear palsy characterized by a loss of self-activation and a compulsive behaviour of the obsessive type is reported. The pathological examination was remarkable for the intensity of pallidal lesions and their diffusion to both the external and internal segments. While the loss of self-activation seemed to result from a damaged cortico-subcortical circuit forming a limbic loop, the compulsive behaviour of the obsessive type may have resulted from the interruption of a frontal-caudal-pallidal-luysian circuit.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease which occurs in immunodepressed subjects and is particularly frequent in AIDS. Some authors having drawn attention to the protean aspect of the disease and claimed that AIDS may lose its basic characteristics and affect the grey matter as well as the white matter, we reviewed a series of 8 patients who had been biopsied and/or autopsied and had been examined at least once by MRI. In this series, contrary to what is regularly observed in toxoplasmic abscesses we did not find any lesion of the grey matter or any mass effect. On the other hand, we confirmed that PLM is not multifocal in all cases and that it course may be interrupted by prolonged remissions. The MRI criteria for PML therefore are reliable, provided multiple T2-weighted slices in coronal plane are performed, clearly showing the anatomy of the white fibres affected. However, it must be borne in mind that HIV-infected patients often have other associated brain pathologies, especially when the immune deficiency increases.

The authors report the clinical and pathological findings in a 46 years old woman with Huntington's chorea and cerebello-olivar atrophy. Eight previously reported cerebellar atrophies in Huntington's chorea with pathological examination are reviewed. The primary or secondary nature of the cerebellar lesions is discussed.

Case report of clinical, pathological and ultrastructural features in an acute spongiform leucoencephalopathy with selective involvement of U fibers. A 52 years old woman exhibited an acute encephalopathy of 2 months duration, with dementia and multifocal impairment of cortical functions. The cerebral cortex was normal. This acute dementia resulted from a diffuse intercortical disconnection. Spongy degeneration was only found in U fibers. No other changes were noted especially in basal ganglia, optics tracts, and spinal cord. The white matter status spongious was related to an intramyelinic oedema. Such intramyelinic oedema is known only in Van Bogaert and Bertrand and Canavan disease, which is quite different, and in toxic encephalopathies, especially those induced by the hexachlorophene and triethyltin. In the present case no drugs or toxins were found. An ovarian carcinoma was found at post-mortem examination.

Three clinico-pathological cases of necrotic myelopathies with a distant malignancy are presented. Two cases had a lymphosarcoma and one case a prostatic carcinoma. They were compared to 13 well studied other cases collected in the literature. These myelopathies were related to solid visceral tumours in 8 cases and to lymphomas in 5 cases. The disease could be individualized on clinical grounds (flaccid paraplegia with bladder and bowell incontinence and sensory loss without clear-cut upper boundary developing over a few weeks with normal CSF and fast impairement of general condition), and, on pathological features. It is characterized by one or several spinal cord necrosis areas, often asymetrical, involving mostly white matter, without any vascular topography. Axons are involved as well as myelin sheats. There is mild inflammation and no specific vascular alteration. There is no metastases in the cord, meninges, vertebral column or nerve root. No vascular occlusion is found. The mechanism of the disease is unknown. The frequent occurence of lymphomas could suggest the presence of immunopathological factors.