G-CSF mediated neutrophil augmentation in a unique case of comorbid idiopathic Parkinson's disease and treatment-resistant schizophrenia on clozapine.

Treatment of psychosis in Parkinson's disease (PD) is challenging; pharmacological options are limited, with clozapine considered most effective. The risk of agranulocytosis restricts the use of clozapine, but, where this occurs, cautious re-challenge with granulocyte stimulating factor can be successful. We present a unique case of a patient who developed early-onset PD on a background of antecedent treatment-resistant schizophrenia, who had been treated effectively with clozapine for over 15 years with no adverse events. However, during a hospital admission intended to optimise her Parkinsonian medications, she developed persistent neutropenia necessitating clozapine discontinuation. Numerous attempts to re-challenge with clozapine failed until augmentation with lithium and G-CSF was trialled. Two doses of G-CSF led to a sustained increase in the neutrophil count, allowing the continuation of clozapine therapy in the 1 year of follow up. This illustrates the potential for G-CSF to be used to facilitate clozapine use in a patient population not described previously. Neutrophil augmentation allowed the sustained continuation of this effective therapy, treating her psychotic symptoms without detriment to her movement disorder. We suggest that G-CSF might be considered as a treatment option in other cases where clozapine-associated neutropenia obstructs its use.

Successful management of persistent distressing neuropsychiatric symptoms by clozapine in a patient suffering from dementia with Lewy bodies.

Dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementia associated with poor prognosis and high carers' burden. Neuropsychiatric symptoms worsen this prognosis and are a high source of distress for service users and their carers. However, there is currently insufficient evidence to support the pharmacological and non-pharmacological management of these symptoms. Acetylcholinesterase inhibitors are the first-line pharmacological option, but challenging risky behaviours may persist despite their use. Antipsychotic medications are indicated in such clinical scenarios, but there is very limited evidence to support the efficacy and safety of these medications for managing neuropsychiatric symptoms in DLB. Hence, we report an individual with DLB with severe distressing persistent visual hallucinations and agitation. After multiple treatment options had failed, clozapine was successfully initiated with substantial improvement in both clinical and functional outcomes. Further studies are warranted for evaluating the efficacy of clozapine in managing neuropsychiatric symptoms in DLB.

Finding a pathological diagnosis for Alzheimer's disease: are inflammatory molecules the answer?

Conventional diagnostic tools for Alzheimer's disease (AD) are currently based on a number of clinical criteria, and a definitive diagnosis still relies on pathological evaluation at autopsy. Moreover, neurodegenerative changes are believed to begin years before clinical presentation. There is therefore an essential need for a reliable AD biomarker to aid in the identification of preclinical disease, early diagnosis, prediction of disease progression and treatment response. There is mounting evidence that chronic inflammatory processes play a fundamental role in the progression of neuropathological changes in AD. Clinical and experimental evidence supports the involvement of inflammatory changes in the early stages of AD, even before the appearance of amyloid deposits. Therefore biomarkers that reflect the inflammatory process in AD hold promise. Tests based on these should preferably be reliable, noninvasive and costeffective, which has led to an increasing focus on the use of blood-based biomarkers. This review considers the current progress in AD inflammatory biomarker research followed by a detailed analysis of two leading putative inflammatory biomarkers: α-2-macroglobulin and clusterin.