Jane Alty

Palliative care for Parkinson’s disease: A summary of the evidence and future directions

Background: Parkinson’s disease is a common, life-limiting, neurodegenerative condition. Despite calls for improved access to palliative care for people with Parkinson’s disease, services have been slow in developing. Obstacles include poor understanding and recognition of palliative care needs, the role for specialist palliative care services and an agreed structure for sustainable palliative care provision. Aim: To summarise the evidence base for palliative care in Parkinson’s disease, linking current understanding with implications for clinical practice and identifying areas for future research. What is known: Convention recognises a final ‘palliative phase’ in Parkinson’s disease, while qualitative studies suggest the presence of palliative care need in Parkinson’s disease from diagnosis. Clinical tools to quantify palliative symptom burden exist and have helped to identify targets for intervention. Dementia is highly prevalent and influences many aspects of palliative care in Parkinson’s disease, with particular implications for end-of-life care and advance care planning. Implications for clinical practice: The ‘palliative phase’ represents a poor entry point for consideration of palliative care need in Parkinson’s disease. An alternative, integrated model of care, promoting collaboration between specialist palliative and neurological services, is discussed, along with some specific palliative interventions. What is unknown: Limited evidence exists regarding timing of palliative interventions, triggers for specialist referral and management of terminal care. Implications for future research: Research examining access to palliative care and management of terminal symptoms will assist development of sustainable, integrated palliative care services for Parkinson’s disease.

A randomized, double-blind, placebo-controlled trial of levetiracetam for dyskinesia in Parkinson's disease†‡§

This randomized double blind, placebo‐controlled crossover study investigated the antidyskinetic effects of levetiracetam in Parkinsons disease.

Cognitive impairment in Parkinson's disease

Cognitive impairment is a significant non-motor symptom of Parkinsons disease (PD). Longitudinal cohort studies have demonstrated that approximately 50% of those with PD develop dementia after 10 years, increasing to over 80% after 20 years. Deficits in cognition can be identified at the time of PD diagnosis in some patients and this mild cognitive impairment (PD-MCI) has been studied extensively over the last decade. Although PD-MCI is a risk factor for developing Parkinsons disease dementia there is evidence to suggest that PD-MCI might consist of distinct subtypes with different pathophysiologies and prognoses. The major pathological correlate of Parkinsons disease dementia is Lewy body deposition in the limbic system and neocortex although Alzheimers related pathology is also an important contributor. Pathological damage causes alteration to neurotransmitter systems within the brain, producing behavioural change. Management of cognitive impairment in PD requires a multidisciplinary approach and accurate communication with patients and relatives is essential.

A practical guide to the differential diagnosis of tremor.

Tremor is, by definition, a rhythmic oscillation of a body part. It is the most prevalent movement disorder in clinical medicine, so doctors working in many specialities and in general practice can expect to encounter it. Most tremors can be classified on the basis of four observable clinical characteristics: anatomical pattern; the relative prominence of the tremor at rest, on maintaining a posture, and with action; tremor frequency; and tremor amplitude. A resting tremor suggests Parkinsons disease, and the diagnosis then depends on a judgement about whether the patient has other signs of parkinsonism. The most common causes of postural tremor are physiological tremor, essential tremor and drug-induced tremor. The differential diagnosis may also include dystonic tremor and psychogenic tremor, while metabolic tremor caused by thyrotoxicosis should be considered in any recent-onset postural tremor. Wilsons disease and fragile X-associated tremor/ataxia syndrome are rarer conditions that may present with tremor and are very important to identify. There is a small but genuine diagnostic grey zone between Parkinsons disease and more benign tremor disorders such as essential tremor and dystonic tremor, in which resting and postural tremor coexist with mild or equivocal non-tremor parkinsonian signs. The authors review clinical features and investigational techniques that may help to discriminate this group of hard-to-classify tremors.

Longitudinal study of levodopa in Parkinson's disease: Effects of the advanced disease phase

Thirty‐four patients have been studied from the time of initiation of pharmacological treatment in a long‐term prospective study of levodopa effects and disease progression in Parkinsons disease. Objective motor scoring of the response to levodopa in defined off states was performed every 3 years. The mean time from the initiation of levodopa treatment to the most recent measurements was 18.2 years. Of 8 patients who are still alive, only 3 had none of the features of the advanced disease phase (dementia, hallucinations, frequent falling). Off‐phase motor function worsened at a yearly rate of 1.9% of the maximum disability score, although the plots of the serial scores showed that the magnitude of the levodopa response is well preserved. There was little difference in the rate of progression between patients with tremor‐dominant and non‐tremor‐dominant motor subtypes. Those who developed dementia had more rapid deterioration of motor scores, with significantly worse off‐phase (P = .008) and on‐phase (P = .03) motor function. A graph of serial scores of patients who have died, aligned for time of death, showed an upward curving trend of motor disability in the last 5 years of the disease course. Its advanced phase may reveal that Parkinsons disease has an exponential pattern of progression.

Computational approaches for understanding the diagnosis and treatment of Parkinson's disease

This study describes how the application of evolutionary algorithms (EAs) can be used to study motor function in humans with Parkinsons disease (PD) and in animal models of PD. Human data is obtained using commercially available sensors via a range of non-invasive procedures that follow conventional clinical practice. EAs can then be used to classify human data for a range of uses, including diagnosis and disease monitoring. New results are presented that demonstrate how EAs can also be used to classify fruit flies with and without genetic mutations that cause Parkinsons by using measurements of the proboscis extension reflex. The case is made for a computational approach that can be applied across human and animal studies of PD and lays the way for evaluation of existing and new drug therapies in a truly objective way.

Study of Levodopa Response in Parkinson's disease: Observations on rates of motor progression

It is important to understand how the rate of motor progression in PD relates to dopaminergic treatment.

What type of tremor did the medieval ‘Tremulous Hand of Worcester’ have?

The thirteenth-century medieval scribe, the ‘Tremulous Hand of Worcester’ is known for the tremor visible in his script. Thorpe & Alty combine historical analysis with the first neurological study of the scribe’s handwriting. After considering various differential diagnoses, they conclude that the balance of evidence favours essential tremor.

Longitudinal study of the levodopa motor response in Parkinson's disease: relationship between cognitive decline and motor function.

In this prospective study of 34 patients with Parkinsons disease (PD), measurements of the short duration levodopa motor response have been performed every 3 years in defined off states. The mean time from initiation of levodopa treatment was 14.8 years, and 17 patients survived to the latest assessment stage. Off phase motor function worsened at a yearly rate of 2.2% of the maximum disability score. The magnitude of the levodopa response is well preserved as the disease progresses, and patients who developed motor fluctuations maintained better on phase motor function than nonfluctuators (P = 0.01). Ten patients, of whom 5 survive, developed dementia. There was no difference in pretreatment disability or initial levodopa response between demented and nondemented subjects. However, dementia was associated with worse on and off motor disability scores after 11 and 14 years (P < 0.001), and a smaller levodopa response magnitude after 14 years (P = 0.008). The plot of sequential scores shows the association between cognitive decline and accelerating increase in motor disability. This suggests that the advanced phase of PD, when Lewy body pathology involves the cerebral cortex, progresses in an exponential rather than linear fashion.

How to use pen and paper tasks to aid tremor diagnosis in the clinic

When a patient presents with tremor, it can be useful to perform a few simple pen and paper tests. In this article, we explain how to maximise the value of handwriting and of drawing Archimedes spirals and straight lines as clinical assessments. These tasks take a matter of seconds to complete but provide a wealth of information that supplements the standard physical examination. They aid the diagnosis of a tremor disorder and can contribute to its longitudinal monitoring. Watching the patient’s upper limb while they write and draw may reveal abnormalities such as bradykinesia, dystonic posturing and distractibility. The finished script and drawings can then be evaluated for frequency, amplitude, direction and symmetry of oscillatory pen movements and for overall scale of penmanship. Essential, dystonic, functional and parkinsonian tremor each has a characteristic pattern of abnormality on these pen and paper tests.