Will Lee

Sex differences in Parkinson's disease.

Sex-related differences in Parkinsons disease (PD) have been recognised, but remain poorly understood. We aimed to further clarify real-life differences in disease experience according to sex, by evaluating quality of life (QoL), demographic and clinical characteristics of PD patients. A cross-sectional survey was conducted on 210 PD patients (129 men, 81 women) attending specialist neurological clinics across three centres. Outcome measures included the motor examination of the Unified Parkinsons Disease Rating Scale (UPDRS-III) and QoL as measured by the 39-item Parkinsons Disease Questionnaire (PDQ-39). A male to female ratio of 1.6:1 was observed. Men reported a greater disease burden than women as noted by higher UPDRS-III scores (27 ± 13 versus 23 ± 13, p=0.032), daily levodopa equivalent doses (898.1 ± 481.3mg versus 750.7 ± 427.2mg, p=0.037) and caregiver reliance (44% versus 29.5%, p=0.039). The UPDRS-III score was significantly associated with sex after controlling for age and disease duration, with men more severely affected (β=-0.165, r(2)=0.101, p=0.028). The PDQ-39 showed men reported lower QoL in activities of daily living (ADL), cognition and communication sub-scales (p<0.05). An association was identified in men between PDQ-39 ADL and cognition sub-scales (r=0.660, p<0.001). Men with an appointed caregiver had a higher PDQ-39 Summary Index (t=3.222, degrees of freedom=122, p=0.002). PD was found to have greater overall impact on the health and well-being of male patients in sub-specialty clinical practice. Our study further supports the need for increased sex-delineated clinical assessment and consideration of potential differences required in the management of PD.

Cognitive testing in the diagnosis of parkinsonian disorders: a critical appraisal of the literature.

A number of cognitive abnormalities have been identified as putative diagnostic markers in neurodegenerative parkinsonism based on statistically significant differences between diseases. The effect sizes of these differences frequently have not been reported, making practical interpretation of the results difficult. The objective of this study was to assess the potential contribution of cognitive testing to the diagnosis of parkinsonian disorders by quantifying effect size of previously identified significant differentiating cognitive features. A Medline search identified 1038 articles. Nineteen studies directly comparing at least 2 of Parkinsons disease, progressive supranuclear palsy, multiple system atrophy, and corticobasal syndrome/degeneration were selected. Cohens d and positive likelihood ratio were calculated as appropriate for cognitive tests showing statistically significant differences between diseases. Clinically useful differences were considered present when Cohens d > 1 or the positive likelihood ratio > 2 and were considered high when Cohens d > 1.94 or the positive likelihood ratio > 10. Only 16 of 141 cognitive tests were found to be highly useful. Cognitive testing was only moderately helpful in separating Parkinsons disease and multiple system atrophy. Inferior performance on phonemic (d = 1.56–2.13) and semantic (d = 1.43–2.13) verbal fluency, the Trail‐Making Test (d = 1.63–1.95) and the Wisconsin Card Sorting Test (d = 1.63–2.22) were moderately to very useful in separating progressive supranuclear palsy from Parkinsons disease and multiple system atrophy. Cognitive testing could not differentiate corticobasal syndrome from other parkinsonian disorders, although sequential orobuccal apraxia was very useful (d = 2.01–2.23). Few of the cognitive tests separating parkinsonian disorders identified from previous studies have sufficient effect size to be practically useful. Even these features must be interpreted in conjunction with other clinical characteristics to be helpful diagnostically.

Validation of a Smartphone Application Measuring Motor Function in Parkinson's Disease.

BACKGROUND Measurement of motor function is critical to the assessment and management of Parkinsons disease. Ambulatory motor assessment has the potential to provide a glimpse of the patients clinical state beyond the consultation. We custom-designed a smartphone application that quantitatively measures hand dexterity and hypothesized that this can give an indication of a patients overall motor function. OBJECTIVE The aims of this study were to (i) validate this smartphone application against MDS-UPDRS motor assessment (MDS-UPDRS-III) and the two-target tapping test; (ii) generate a prediction model for MDS-UPDRS-III; (iii) assess repeatability of our smartphone application and (iv) examine compliance and user-satisfaction of this application. METHODS 103 patients with Parkinsons disease were recruited from two movement disorders clinics. After initial assessment, a group of patients underwent repeat assessment within two weeks. Patients were invited to use the smartphone application at home over three days, followed by a survey to assess their experience. RESULTS Significant correlation between key smartphone application test parameters and MDS-UPDRS-III (r = 0.281-0.608, p < 0.0001) was demonstrated. A prediction model based on these parameters accounted for 52.3% of variation in MDS-UPDRS-III (R2 = 0.523, F(4,93) = 25.48, p < 0.0001). Forty-eight patients underwent repeat assessment under identical clinical conditions. Repeatability of key smartphone application tests parameters and predicted MDS-UPDRS-III was moderate to strong (intraclass correlation coefficient 0.584-0.763, p < 0.0001). The follow-up survey identified that our patients were very comfortable with the smartphone application and mobile technology. CONCLUSIONS Our smartphone application demonstrated satisfactory repeatability and validity when measured against MDS-UPDRS-III. Its performance is acceptable considering our smartphone application measures hand dexterity only.

Stroke and Takotsubo cardiomyopathy: Is there more than just cause and effect?

Takotsubo cardiomyopathy has been described as a consequence of stroke or a cardioembolic source of stroke. We present the case of a 43 year-old woman who suffered from Takotsubo cardiomyopathy and subsequently developed a large left cerebellar infarct without significant neurological deficits nor evidence of a cardioembolic cause. Catecholamine excess has been postulated to cause myocardial stunning in Takotsubo cardiomyopathy and some cases of cerebral ischaemia. In this case, the concurrent occurrence of Takotsubo cardiomyopathy and stroke without an identifiable source suggests that there may be a possible unifying pathogenetic mechanism.

TSH‐secreting pituitary carcinoma with intrathecal drop metastases

PEG precipitation. This test is simple, available and inexpensive, able to detect all types of insulin-binding antibodies irrespective of class (e.g. IgG, IgM and IgA) or subclass. Kit tests that target only one class such as IgG may be considered informative in positive cases; however, it must be regarded inconclusive if the outcome is negative, and searching for other insulin antibodies of different class such as IgM or IgA must continue. Investigating the presence of receptor antibodies should be considered in cases of unexplained hypoglycaemia with or without elevated serum insulin and C-peptide and in whom exclusion of all forms of IAH per se is considered necessary. Commercial kits for insulin-receptor antibodies are available albeit expensive. In conclusion, Early testing for insulin-binding antibodies can help in differential diagnosis of hypoglycaemia because a positive result should (i) raise the possibility of insulin autoimmune hypoglycaemia, irrespective of the underlying cause, (ii) exclude surreptitious insulin administration when insulin is high and C-peptide is low/undetectable, (iii) raise the possibility of analytical interference and false immunoassay results of insulin, C-peptide and proinsulin masquerading as insulinoma and (iv) raise the possibility of simultaneous presence of insulin-binding and insulinreceptors antibodies if the outcome of biochemical investigations is incongruous.

A cross-sectional study of clinical management, and provision of health services and their utilisation, by patients with Parkinson's disease in urban and regional Victoria.

Our objective was to evaluate and compare clinical management, utilisation of health services and quality of life (QoL) in patients with Parkinsons disease (PD) attending clinics in urban and regional Victoria. A cross-sectional survey was conducted on 210 patients with PD attending specialist neurological clinics in a regional area (Ballarat) (n=97), and an urban area (Melbourne) (n=113), Victoria. Demographic characteristics of patients with PD, QoL, patterns of disease and management and utilisation of medical and allied health services were analysed. Compared to patients with PD from urban clinics, patients in the regional clinic were significantly older and were diagnosed at a later age with a shorter duration of treatment (all p<0.05). Despite no significant difference in disease severity (measured by Unified Parkinsons Disease Rating Scale scores) between the groups, patients in the urban clinic reported a lower QoL (p=0.003). Patients in the regional clinic were more satisfied with their treatment, despite seeing their medical specialist less frequently (p<0.001) and having a higher rate of early misdiagnosis (p=0.015). Patients from regional clinics reported a poorer understanding of their illness than patients in the urban clinic (p=0.049). Half of all respondents were interested in using telemedicine services. Two-thirds (71%) of all patients used allied health services, with patients in the urban clinic utilising more and desiring greater access to these services (p<0.05). In conclusion, we found significant differences in the presentation, management and use of health services between patients accessing regional and urban PD clinics in Victoria. Telemedicine may be an effective, and even desirable, method for facilitating improved diagnosis and referral for appropriate therapies.

Clinical, laboratory and electrophysiological features of Morvan's Fibrillary Chorea

Morvans Fibrillary Chorea (MFC) is a rare autoimmune disorder causally associated with auto-antibodies directed at the voltage-gated potassium channel (VGKC-Abs). It classically presents with sleep disturbances, neuromyotonia and dysautonomia. We aimed to systematically characterise the features of MFC by describing a patient and reviewing published literature. Case notes of 27 patients with MFC (one from our clinic and 26 from the literature) were reviewed and clinical data were extracted and analysed. We found that MFC mainly affects men (96%) and runs a subacute course over months. Neoplasia (56%), VGKC-Abs positivity (79%) and autoimmunity (41%) are frequent associations. Myokymia, insomnia and hyperhidrosis were almost universally described. Other autonomic features were present in 63% with the most common being cardiovascular and bowel disturbances. Clinical, radiological or electroencephalographical features of limbic encephalitis were present in 19% of patients. Outcome was fair with an overall recovery rate of 78%. All patients with malignancies underwent surgery. Immunotherapies including corticosteroids, intravenous immunoglobulins and plasma exchange were instituted in 22 patients and 19 (86%) responded. Of all symptomatic treatments tried, carbamazepine, phenytoin, sodium valproate, levetiracetam and niaprazine were found to be effective. The broad clinical spectrum of VGKC-Abs diseases can make early recognition of MFC difficult. Myokymia, insomnia and hyperhidrosis are invariably present. There may be abnormalities on cerebrospinal fluid testing and VGKC-Abs can occasionally be absent. Early initiation of immunotherapies and malignancy screening are important to prevent adverse outcomes in a condition that generally responds favourably to treatment.

Vertebrobasilar ischaemia presenting as recurrent isolated vertigo

Abstract Chronic recurrent isolated vertigo is an uncommon manifestation of vertebrobasilar ischaemia. We report a 43-year-old female with 12-month history of recurrent attacks of isolated vertigo who presented with acute pontine infarctions. Clinical examination and vestibular function testing showed bilateral vestibular hypofunction affecting the horizontal and posterior semicircular canals and right saccule. Diffusion-weighted magnetic resonance imaging (MRI) demonstrated acute bilateral pontine infarcts and significant vertebrobasilar stenoses. The findings of recurrent isolated vertigo and bilateral vestibular hypofunction should not prevent a search for vertebrobasilar ischaemia, particularly in the presence of vascular risk factors.

Levodopa‐carbidopa intestinal gel: is the naso‐jejunal phase a redundant convention?

Levodopa‐carbidopa intestinal gel (LCIG) is an effective treatment for Parkinson disease. Initiating therapy involves an initial naso‐jejunal (NJ) titration phase. The NJ phase is prolonged with significant morbidity. The aim of this study is to assess the impact of proceeding without the NJ phase on resource utilisation and the outcomes of patients. Twenty‐five patients were started on LCIG using the patients existing levodopa equivalent dose (LED). We recorded change in LED, length of hospital stay, readmission rates and use of outpatient services and clinical outcomes within 6 months. The median length of stay was 4.5 days. Patients had four outpatient clinic reviews and 2.5 community nurse contacts within 6 months. There was no significant change in daily LED on discharge (P = 0.56). There were significant improvements in all Unified Parkinson Disease Rating Scale subscores (P < 0.05), the Freezing of Gait scale (P < 0.01) and Parkinson Disease Quality Of Life 39 score (P < 0.01). Initiating LCIG without the NJ phase resulted in short admissions, a minimal outpatient burden and no significant requirement for dose titration while producing good clinical outcomes.

Subjective perception of sleep benefit in Parkinson's disease: Valid or irrelevant?

INTRODUCTION The phenomenon of sleep benefit (SB) in Parkinsons disease (PD), whereby waking motor function is improved despite no dopaminergic treatment overnight, is controversial. Previous studies suggested a significant discrepancy between subjective functional and objective motor improvement. The aim of this study was to determine how well subjective reporting of SB correlates with objective measures and if true motor improvement can be predicted by a standardized questionnaire. METHODS Ninety-two patients with PD participated. A structured questionnaire was developed to assess subjective SB. Quantitative motor assessment was performed using a validated smartphone application. Objective motor SB was considered to be present when the waking motor function was similar or superior to the daytime on-state. RESULTS Twenty (22%) patients showed objective motor improvement on waking compared to end-of-dose. Most patients (77%) reported subjective SB without corresponding objective motor benefit. Our structured questionnaire could not predict Motor SB. The ability to delay morning medications and a perception of indifference or paradoxical worsening following the morning levodopa dose may suggest Motor SB. CONCLUSIONS Most patients experience subjective SB with no measureable motor improvement. This perceived benefit could be related to non-motor improvement that is distinctly different to objective motor benefit.