Background Dissociative seizures are paroxysmal events resembling epilepsy or syncope with characteristic features that allow them to be distinguished from other medical conditions. We aimed to compare the effectiveness of cognitive behavioural therapy (CBT) plus standardised medical care with standardised medical care alone for the reduction of dissociative seizure frequency.
MethodsIn this pragmatic, parallel-arm, multicentre randomised controlled trial, we initially recruited participants at 27 neurology or epilepsy services in England, Scotland, and Wales. Adults (≥18 years) who had dissociative seizures in the previous 8 weeks and no epileptic seizures in the previous 12 months were subsequently randomly assigned (1:1) from 17 liaison or neuropsychiatry services following psychiatric assessment, to receive standardised medical care or CBT plus standardised medical care, using a web-based system. Randomisation was stratified by neuropsychiatry or liaison psychiatry recruitment site. The trial manager, chief investigator, all treating clinicians, and patients were aware of treatment allocation, but outcome data collectors and trial statisticians were unaware of treatment allocation. Patients were followed up 6 months and 12 months after randomisation. The primary outcome was monthly dissociative seizure frequency (ie, frequency in the previous 4 weeks) assessed at 12 months. Secondary outcomes assessed at 12 months were: seizure severity (intensity) and bothersomeness; longest period of seizure freedom in the previous 6 months; complete seizure freedom in the previous 3 months; a greater than 50% reduction in seizure frequency relative to baseline; changes in dissociative seizures (rated by others); health-related quality of life; psychosocial functioning; psychiatric symptoms, psychological distress, and somatic symptom burden; and clinical impression of improvement and satisfaction. p values and statistical significance for outcomes were reported without correction for multiple comparisons as per our protocol. Primary and secondary outcomes were assessed in the intention-to-treat population with multiple imputation for missing observations. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN05681227, and ClinicalTrials.gov, NCT02325544.
Progressive multifocal leukoencephalopathy (PML) is a usually fatal cerebral white matter disease found in patients with human immunodeficiency virus infection and other immunocompromised states. We present the case of a 63-year-old woman with polycythemia vera who developed a progressive focal neurological deficit with white matter abnormalities on magnetic resonance images of the brain that was proved on biopsy to be PML. She was treated with the serotonin reuptake inhibitor mirtazapine and remains neurologically stable, with resolution of cerebral lesions, >2 years after diagnosis. We propose that mirtazapine should be investigated further for use in PML.
Peripheral nerve disorders are frequent complications of HIV disease. Distal symmetrical polyneuropathy (DSP) is the most common peripheral nerve disorder associated with HIV and occurs in over one third of infected patients but may occur in up to 67% if asymptomatic patients are included. Risk factors for DSP include increased age, advanced HIV disease, and history of "d-drugs" or other neurotoxic drugs. The primary manifestations of polyneuropathy are slowly progressive numbness and paresthesias, with burning sensations in the feet usually in a symmetrical pattern. The etiology of HIV-associated DSP is unknown, although neurotoxic effects of cytokines, toxicity of HIV proteins, and mitochondrial damage have been implicated. The current treatment for HIV-associated DSP is symptomatic, with pain modifying medications, including anti-inflammatory agents, opioids, antidepressants, antiepileptics, topical anesthetics, and capsaicin. Sustained virologic control may improve DSP. Novel therapies such as -acetyl-l-carnitine or neurotrophic factors are being studied for treatment of DSP.
There is no effective treatment for HIV-associated myelopathy (HIVM). The introduction of highly active antiretroviral therapy (HAART) has made little difference to its natural history. Spinal cord pathology reveals vacuolization and inflammation. Intravenous immunoglobulin (IVIg) is used successfully in a number of inflammatory conditions associated with HIV. In view of the potential for reversibility of the inflammatory response in HIVM, we treated 17 patients with IVIg twice over a 56-day study period. There was improvement in composite Medical Research Council (MRC) strength scores 28 days following the first infusion (increase in score: 3.94; p = 0.021). The second infusion did not produce further improvement, however there was little reduction from peak strength. These pilot data suggest that further investigation of the use of IVIg in HIVM is warranted.
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