[Progressive multifocal leukoencephalopathy in a non-AIDS patient: high efficiency of combined cytarabine and cidofovir]. / Leucoencéphalite multifocale progressive en dehors du sida: efficacité de l'association cytarabine-cidofovir.

INTRODUCTION: Progressive multifocal leukoencephalopathy (PML) is an opportunistic infection of the central nervous system, occurring in immunocompromised patients. Treatment, not codified to date, is more often inefficient with a rapid and fatal deterioration. CASE RECORD: A 48-year-old woman, treated with immunosuppressant agents for systemic lupus, presented with PML mimicking neurolupus flare. A complete remission was obtained with cytarabine and cidofovir. CONCLUSION: Combined cytarabine and cidofovir appears a promising therapeutic option in PML associated with autoimmune systemic disorders.

[New trends in progressive multifocal leukoencephalopathy]. / Données récentes sur la leucoencéphalite multifocale progressive.

Infection by Polyomavirus JC is a model of chronic active viral infection, closely controlled by the immune system. Progressive multifocal leucoencephalopathy (PML) is a deadly demyelinating disease of the central nervous system, consecutive to the lytic infection of oligodendrocytes by JC virus. Reactivation of JC virus occurs only in the setting of severe cellular immune deficiency. During the last 25 years, the incidence of PML has significantly increased related to the AIDS pandemic and, more recently, to the growing use of immunosuppressive drugs. There is no specific antiviral treatment for PML. Nevertheless, the availability of highly active antiretroviral therapy has changed the clinical course of PML in HIV-infected individuals. One-year mortality has decreased from 90 percent to approximately 50 percent as a result of reconstitution of the immune system. Recent advances in JC virus biology give new perspectives to the pathogenesis of PML. New trends in the understanding of the cellular immune response against the JC virus have direct implications for patient management and may lead to develop future strategy of immunotherapies for PML.

Survival improvement of AIDS-related progressive multifocal leukoencephalopathy in the era of protease inhibitors. Clinical Epidemiology Group. French Hospital Database on HIV.

OBJECTIVE: To estimate the change in survival of patients with AIDS-related progressive multifocal leukoencephalopathy (PML), in relation to the introduction of protease inhibitors (PI). DESIGN: The French Hospital Database on HIV (FHDH) is a prospective cohort of 70 224 HIV-infected subjects. This study included the patients diagnosed with PML between 1 July 1995 and 30 June 1997. PML diagnosis was both presumptive and confirmed. We compared the survival probability according to the diagnosis period (period 1 or 2, before or after introduction of PI in France on 1 April 1996). Cox's model was used to calculate the relative hazards of death according to the antiretroviral regimen. RESULTS: The study included 246 patients, 109 diagnosed during period 1 and 137 during period 2. In all, 131 patients received an antiretroviral combination that included PI. By 31 December 1997, a total of 131 deaths had been reported. The probability of survival at 6 months for patients from period 2 was nearly twice as high as for patients from period 1 (60.5 versus 34.5%). In comparison with patients receiving no treatment, the risk of death in patients on combination therapy not including PI was reduced by 38% [relative hazard (RH) 0.62, 95% confidence interval (CI) (0.41; 0.95), P = 0.026] and in patients on combination therapy with PI, by 63% [RH 0.37, 95% CI (0.22; 0.64), P = 0.0004]. CONCLUSION: This study of a large cohort of patients diagnosed with PML (n = 246), provides evidence that a combination antiretroviral regimen, especially one including PI, confers marked survival benefits.

Induction and maintenance therapy of cytomegalovirus central nervous system infection in HIV-infected patients.

OBJECTIVE: To evaluate the efficacy and safety of the foscarnet-ganciclovir combination in induction therapy (IT) and maintenance therapy (MT) for cytomegalovirus (CMV) central neurological disorders in HIV-infected patients. DESIGN: An open pilot non-comparative multicentre study. METHODS: Thirty-one patients with acute CMV encephalitis (CMVe) (n = 17) or CMV myelitis (CMVm) (n = 14) during the era before highly active antiretroviral therapy (HAART) received intravenous IT with foscarnet 90 mg/kg plus ganciclovir 5 mg/kg twice a day followed by MT. The primary endpoint was clinical efficacy, assessed at the end of the induction phase. RESULTS: The foscarnet-ganciclovir combination in IT resulted in a 74% (23 out of 31 patients) clinical improvement or stabilization. Eight patients did not respond clinically. Side-effects leading to drug discontinuation occurred in 10 patients during IT. Among the 23 patients who qualified for the maintenance phase, CMV disease progressed in 10, with a median time to the first relapse of 126 days (range 64-264 days). Overall, the median survival time was 3 months [95% confidence interval (CI), 2-4 months]. CONCLUSION: The combination of foscarnet and ganciclovir can safely be used for CMV central nervous system (CNS) infection, with an improvement or stabilization in 74% of patients. Life-long MT with this combination is recommended as long as the immune system is profoundly impaired.

Increased sperm count in 25 cases of idiopathic normogonadotropic oligospermia following treatment with tamoxifen.

Twenty-five subfertile men, all presenting with idiopathic normogonadotropic oligospermia, were treated with tamoxifen (20 mg/day) for 4 to 12 months. Semen analysis was performed twice before treatment and at least twice after 3 to 12 months of treatment. In 14 patients, serum luteinizing hormone (LH), serum follicle-stimulating hormone (FSH), and plasma testosterone (T) were assayed before treatment, then again after 2 weeks and 12 weeks of treatment. Semen volume, sperm motility, and sperm morphologic characteristics were not modified by tamoxifen. Conversely, a twofold increase of both the mean sperm concentration and the mean total sperm count per ejaculate was observed during treatment (P less than 0.001). Mean values of T, LH, and FSH increased during treatment, but the difference was only significant for T (P less than 0.001) and FSH (P less than 0.05). Ten pregnancies (40% of cases) were reported during the 161 months of treatment.

[EEG value for the prediction of the evolution of Alzheimer's type dementia]. / Intérêt de l'EEG pour la prédiction de l'évolution des démences de type Alzheimer.

Twenty patients selected as probable dementia of the Alzheimer type (DAT) have been examined two times during a mean follow-up period of 14.5 months. Two groups have been distinguished at the end of this period: a cognitively impaired one and a stable one. EEG features at T1, at T2 or the difference T1-T2 does not allow an accurate and predictive discrimination between the two groups. But we cannot conclude that EEG is useless for prediction of the rate of progression of the disease in DAT because most of the cognitively stable patients are also stable for mean frequency. So mean frequency could be an interesting marker of evolutivity but this to be tested with more patients including more subjects reaching the severe stage of dementia.

[Arguments for cerebral dysfunction in obsessive-compulsive disorder. A review and synthesis of the literature]. / Arguments en faveur d'un dysfonctionnement cérébral dans le trouble obsessionnel-compulsif. Revue et synthèse de la littérature.

Until recently, particular interest was focalized on the association between Obsessive Compulsive Disorder (OCD) and biochemical markers, for testing the biological hypothesis. The neurotransmitter, most involved in OCD, seems actually to be serotonin. In contrast, few studies were concentrated on searching for the site of dysfunction in specific areas of the brain. Expanding exploration methods of the central nervous system (computerized EEG, evoked potentials, positions emission tomography...) and their recent application in OCD have given more evidence for the validity of the "neurodysfunctional" hypothesis and the localization of the dysfunction in OCD.

[The possible endometrial risk of ovarian stimulation. Apropos of 3 cases]. / Du risque endométrial de la stimulation ovarienne. A propos de trois cas.

Three cases of adenomatous hyperplasia of the endometrium--one of them degenerated--have been reported in young women provided with ovulation stimulation. The association between these hormonal therapies and the adenocarcinoma or its antecedents signs, is particularly disturbing. However, it's difficult to establish a relationship between cause and effect. Indeed the women who suffer from an ovarian sterility are a group exposed to a cancer of the endometrium independently of any other iatrogenic agent. The method of detection is yet to be found, as is the mode of conduct which can reconcile the risk of a carcinoma and the desire of pregnancy.

[Proceedings: Sulpiride effects on plasmatic gonadotropins in women (author's transl)]. / Evolution des gonadotrophines plasmatiques féminines sous sulpiride

The study of longitudinal evolution of plasmatic gonadotropins in women receiving sulpirid, a psychotropic drug with a strong anti-ovulatory effect, shows the coexistence of anovulation and the peristance of a physiological pattern of gonadotropins during the first cycle of treatment. It also shows the persistance of LH peaks comparable to preovulatory levels more than one year after the initiation of therapy. However, the basal line became very unsteady. This study suggests the presence of two types of perturbations with sulpirid. A hypothalamic-hypophyseal mild action and, an ovarian resistance to gonadotropins resulting from the hyperprolactinism induced by sulpirid.

[From embryogenesis to pathogenesis of effects of diethylstilbestrol on the female genital tract]. / De l'embryogenèse à la pathogénie des actions du diéthylstilbestrol sur le tractus génital féminin.

From studies on embryogenesis, the authors describe the development, not conditioned by sex steroids, of the upper female genital tract and, in particular, the formation of its cervico-vaginal portion and the shaping of the uterine cervix in about the 16th week of pregnancy. Basing themselves on the physiology of the foeto-placental unit and on the hormonal profile of the foetal ovary, they show that the action of oestrogens on the foetal uterine cervix can be observed only from the 32nd week onward. The action of diethylstilboestrol--a potent oestrogen that is not steroidal and therefore not degraded by foetal metabolism--on the foetal genital tract is explained. An excessive development of the uterine canal caudal part determines structural anomalies of the uterine cervix at birth, the T shape of the uterine cavity and the vaginal diaphragms. The aetiogenesis of clear-cell adenocarcinoma in the cervico-vaginal portion is discussed.

[Lesions of the spinal cord in HIV infection]. / Atteintes de la moelle épinière au cours de l'infection par le VIH.

Neurological lesions are frequent complications of human immunodeficiency virus (HIV) infections. Organs involved include the brain, peripheral nerves and muscles. Since the widespread use of immunodepressive agents, spinal cord complications have also appeared although poorly documented in the literature. We observed six cases of spinal cord involvement which help indicate the modalities of practical management. In the first case, a 45-year old HIV1 + male presented dysesthesia evolving progressively over the T10 to L2 zones leading to the diagnosis of spinal cord toxoplasmosis. A gait disorder was the first sign in the second case, a 60-year old HIV1 + male. Neurological involvement progressed and the patient developed paraparesia, decreased muscular force with hypoesthesia and impaired proprioception of the lower limbs. Further complications led to coma and death and on autopsy, the patient was found to have cytomegalovirus myeloencephalitis. A 21 HIV1 + haemophiliac was our third case. Here paraplegia resulted from epidural compression due to Burkitt malignant lymphocytosis. The aggravation of paresthesia of the lower limbs, complicated by painful dysesthesia and proximal motor deficiency led to the suspected diagnosis of HIV-related myelitis in a particularly complicated case in a 52-year old seropositive male. In the fifth case, HIV infection led to major demelinization of the cervical and dorsal spinal cord due to toxoplasmosis and vacuolar myelopathy. In the sixth case, acute myelitis in an HIV2 positive male regressed spontaneously in 15 days. In clinical practice, spinal cord complications would appear to be frequent but less so than brain involvement. In the future, a better understanding of these complications should lead to specific identification of spinal cord signs in the neurological symptomatology of patients with HIV infection and allow adapted specific management.

[Spinal tuberculous arachnoiditis]. / Arachnoïdites tuberculeuses spinales.

Tuberculous arachnoiditis of the spine is a rare complication of tuberculous meningitis and can occur despite correct treatment. We report two cases of arachnoiditis in patients with tuberculous meningitis. In both cases, clinical signs included flaccid paraparesia and sphincter dystonia. Evidence for diagnosis was obtained with magnetic resonance imaging of the lombosacral spine after a 3 or 11 week course. Adding corticosteroids to the anti-tuberculosis therapy provided spectacular clinical improvement within 8 days in both cases. The diagnosis of tuberculous arachnoiditis of the spine is often made late but can be confirmed easily with magnetic resonance imaging. Our cases emphasize the importance of oral corticosteroid therapy to avoid severe sequellae.

[Value of bifocal stereotaxic destruction in case of dyskinesia in patients with a motor deficit of cerebral origin]. / Intérêts de la destruction stéréotaxique bifocale en cas de dyskinésies chez des patients ayant une infirmité motrice d'origine cérébrale.

Authors report a study concerning 12 dyskinetic patients with cerebral palsy. The clinical pre-operative examination shows that many signs and symptoms are associated: volitional and postural dyskinesia, athetosis and dystonia, pyramidal deficit and spasticity. Talairach's stereotactic methodology has been used for bifocal (VPL thalamic nucleus and internal pallidum) Yttrium 90 implantation. After stereotactic bifocal lesions, involuntary movements have been reduced in 45.5% of cases and have disappeared in 27% of cases. Impairment of previous motor deficit has been observed in 3% of cases; volitional and postural dyskinesia seems to be the most curable symptomatology. Clinical results in athetoid involuntary movements and dystonia are less rewarding. Because of important anatomical modifications often observed cerebral palsy patients, the authors stress the interest of individual acute neurophysiological study and discuss about the stereotactic targets and the modalities of destruction. They insist upon the necessity of rigorous selection of indications based on acute clinical examination in the perspective of improvement of global functional capacities.

[Neurospychiatric symptoms in HIV infected patients and the role of efavirenz]. / Troubles neuropsychiatriques chez les patients infectés par le VIH et rôle de l'efavirenz.

Efavirenz has now become commonly used to treat HIV infection. Neuropsychiatric disorders have been reported in patients treated with efavirenz. Several factors often make it hard to determine the cause of these disorders: HIV infected patients take many different drugs, they may suffer from various organ diseases, and may also be heavily affected by problems in their everyday life. The French experts group working on neuropsychiatric side effects of efavirenz has undertaken a review of these disorders with the aim to identify: (1) semiology, (2) epidemiology in the global population, in HIV infected patients, and in patients treated with efavirenz. The expert group suggests recommendations to manage these disorders.

Treatment of limbic encephalitis with anti-glioma-inactivated 1 (LGI1) antibodies.

We report a 72-year-old patient who developed acute limbic encephalitis initially considered of uncertain aetiology. Detailed information on clinical presentation, MRI appearance, antibody levels, cognitive impairment assessment, treatment and evolution of the patient is reported here. Since the early 2000s, many antibodies implied in central nervous system autoimmune disorders have been identified. Anti-glioma-inactivated 1 (LGI1) antibodies have been recently identified as associated with limbic encephalitis, as was the case in our patient.

Survival after neuroAIDS: association with antiretroviral CNS Penetration-Effectiveness score.

OBJECTIVE: We examined if the CNS Penetration-Effectiveness (CPE) score of antiretroviral drugs was associated with survival after a diagnosis of HIV-related encephalopathy, progressive multifocal leukoencephalopathy (PML), cerebral toxoplasmosis, or cryptococcal meningitis. METHODS: Using data from the FHDH-ANRS CO4, we compared the survival of 9,932 HIV-infected patients diagnosed with a first neurologic AIDS-defining event in the pre-combination antiretroviral therapy (cART) (1992-1995), early cART (1996-1998), or late cART (1999-2004) periods. Follow-up was subdivided (CPE < 1.5 and CPE ≥ 1.5), and relative rates (RR) of death were estimated using multivariable Poisson regression models. RESULTS: In the pre-cART and early cART periods, regimens with CPE ≥ 1.5 were associated with lower mortality after HIV-related encephalopathy (RR 0.64; 95% confidence interval [CI] 0.47-0.86 and RR 0.45; 95% CI 0.35-0.58) and after PML (RR 0.79; 95% CI 0.55-1.12 and RR 0.45; 95% CI 0.31-0.65), compared to regimens with CPE < 1.5, while in the late cART period there was no association between the CPE score and the mortality. A higher CPE score was also associated with a lower mortality in all periods after cerebral toxoplasmosis (RR 0.68, 95% CI 0.56-0.84) or cryptococcal meningitis (RR 0.50, 95% CI 0.34-0.74). Whatever the neurologic event, these associations were not maintained after adjustment on updated plasma HIV-RNA (missing, <500, ≥500 copies/mL) with RR ranging from 0.82 (95% CI 0.36-1.91) to 1.02 (0.69-1.52). CONCLUSION: At the beginning of the cART era, the CPE score was of importance for survival after severe neurologic event, while in the late cART period, the additional effect of CPE score vanished with more powerful antiretroviral regimens associated with plasma viral load control.