New insights in radiation-induced leukoencephalopathy: a prospective cross-sectional study.

BACKGROUND: Radiation-induced leukoencephalopathy (RIL) is the most threatening delayed complication of cerebral radiotherapy (RT) and remains roughly defined by cognitive dysfunction associated with diffuse FLAIR MRI white matter hyperintensities after brain irradiation. We documented clinical, neuropsychological, and radiological aspects of RI in order to refine diagnostic criteria. METHODS: Patients referred to our center for deterioration in cognitive complaint at least 6 months after completing a focal or whole brain RT underwent a systematic cross-sectional assessment including clinical examination, neuropsychological tests, and a standardized MRI protocol. Patients with progressive tumor were excluded. RESULTS: Forty patients were prospectively enrolled. Of these, 26 had received a focal RT, median dose of 53 Gy (range 50 to 60), and 14 had received a whole brain RT, median dose of 30 Gy. Cognitive complaints, gait apraxia, and urinary troubles were reported in 100, 67, and 38% of cases, respectively. On neuropsychological examination, patients displayed a global and severe cognitive decline through a subcortical frontal mode. The cognitive changes observed were not hippocampic, but related to executive dysfunction. On MRI, 68% of the patients had extensive FLAIR hyperintensities with anterior predominance, 87% had brain atrophy, and 21% had intraparenchymal cysts. T2*-weighted MRI showed small asignal areas in 53% of the patients. These abnormalities are evocative of cerebral small vessel disease. Fractional anisotropy in the corpus callosum correlated with the cognitive evaluation. No differentiation in terms of cognitive and MRI features could be made between patients treated with focal brain RT (glioma) and patients treated with WBRT (for brain metastases or PCNSL). CONCLUSIONS: RIL can be defined by clinical symptoms (subcortical frontal decline, gait apraxia, urinary incontinence) and MRI criteria (cortico-subcortical atrophy, spread FLAIR HI, T2* asignals). This condition mimics a diffuse progressive cerebral small vessel disease triggered by RT, independent of RT protocol.

Ebola Virus-Related Encephalitis.

Ebola patients frequently exhibit behavioral modifications with ideation slowing and aggressiveness, sometimes contrasting with mild severity of Ebola disease. We performed lumbar punctures in 3 patients with this presentation and found Ebola virus in all cerebrospinal fluid samples. This discovery helps to discuss the concept of a specific Ebola virus encephalitis.

Severe meningo-radiculo-neuritis associated with ipilimumab.

PURPOSE: Ipilimumab is a T-cell-potentiating monoclonal antibody directed against cytotoxic T-lymphocyte antigen-4 (CTLA-4) to promote antitumoural immunity. In phase III trials, ipilimumab was shown to be the first agent to improve survival in advanced melanoma patients, regardless of previous treatment. We report a case of severe neurologic disease after ipilimumab treatment. PATIENT AND METHODS: Neurologic symptoms including facial diplegia, tetraplegia, areflexia progressed with time a few days after the fourth monthly ipilimumab infusion. Analysis of the cerebro-spinal fluid showed elevated proteinorachy and lymphocytic meningitis. Despite high doses of steroids and symptomatic treatment, the symptoms worsened. RESULTS: Veinoglobulins were then infused and the patient began to improve and recovered almost normal activity two years later. CONCLUSION: The adverse event profile associated with ipilimumab was primarily immune-related. This is the first case in which such a severe event has been reported.

[Tremor/ataxia syndrome related to Fragile X premutation]. / Syndrome tremblement-ataxie lié à une prémutation de l'X fragile.

The FXTAS syndrome (Fragile X-associated tremor/ataxia syndrome) is a specific neurodegenerative syndrome affecting subjects carrying a premutation of the FMR1 (fragile X mental retardation 1) gene. It affects mainly men with the premutation and aged more than 50 years. This syndrome is separate and distinct from the fragile X syndrome. The FXTAS syndrome remains underestimated today. It should be considered in patients older than 50 years with tremors and cerebellar ataxia, especially when Parkinson disease or cognitive disorders are present or when there is a family history of infertility, early menopause, or mental retardation. In these patients, hyperintense signals of mid-cerebellar peduncle images on T2 and FLAIR MRI justify genetic testing for the FMR1 premutation.

Brain damage from anticancer treatments in adults.

PURPOSE OF REVIEW: Treatment-induced brain toxicity remains a major cause of morbidity in adult patients with cancer. Contrasting with the 40-year-old unresolved controversy about the primary damaging event (vascular versus parenchymal) in the physiopathology, numerous prospective clinical trials have recently addressed the question of brain toxicity. Despite remarkable efforts in methodological design, they often only partially answer the questions of which treatment modalities are responsible, which brain functions are mainly impaired, how long the impairment duration is and which characteristics make patients vulnerable. RECENT FINDINGS: Real advances in the design of safer radiation procedures have been counterbalanced by a wider use of combined radiotherapy-chemotherapy regimens, the development of radiosurgery and the increasing number of long-term survivors. Although classic radionecrosis or chemonecrosis has become less common, more subtle changes such as progressive cognitive dysfunction are increasingly reported after radiotherapy (radiation-induced leukoencephalopathy) or chemotherapy, administered alone or in combination as reviewed here. The methodological aspects of published studies are questioned and suggestions are provided that may improve the design of future trials. SUMMARY: The abovementioned issue is of clinical importance given the number of patients treated for brain tumors, including patients with brain metastases, and the number of patients who are at high risk for brain metastasis who could benefit from prophylactic cranial irradiation. Moreover, drugs used in nonbrain tumors are now recognized to impair brain normal functioning.

[Langerhans cell histiocytosis in an adult patient associated with sclerosing cholangitis and cerebellar atrophy]. / Histiocytose langerhansienne de l'adulte avec cholangite sclérosante et atrophie cérébelleuse.

Langerhans' cell histiocytosis is a disorder in children or young adults, characterized by clonal proliferation of histiocytic cells, staining for CD1a, with uni or multifocal organ involvement. It's a rare condition in adults. We report a case of Langerhans' cell histiocytosis in an adult with sclerosing cholangitis which rapidly progressed to fatal liver failure and progressive cerebellar atrophy. Langerhans cell histiocytosis is a rare cause of sclerosing cholangititis in adults.

[Psychological and neuropsychological problems in multiple sclerosis]. / Troubles psychiques et neuropsychologiques dans la sclérose en plaques.

Neuropsychological investigations have demonstrated that cognitive disorders are common (about 60%) in patients with multiple sclerosis. 22 patients and 22 controls participated in the study with a review of literature. The cognitive dysfunction may be termed a subcortical white matter dementia. The hallmarks are: forgetfulness, reduced speed of information processing, impaired attention and slowness of thought processes, impaired ability to manipulate acquired knowledge. Psychiatric disturbance have also high prevalence: emotional or personality changes, depression. Pathological laughing and crying are classical but not well understood. This intellectual and emotional changes in multiple sclerosis are studied by adapted psychometric psychiatric examination. Correlation of magnetic resonance imaging with neuropsychological testing is now demonstrated. Total lesion score is the best predictor of cognitive deficits, cerebral atrophy and lesions of the corpus collosium also. Neuropsychological rehabilitation techniques and symptomatic treatments must be applied to patients with multiple sclerosis.