Improving Conversations about Parkinson's Dementia.

BACKGROUND: People with Parkinson's disease (PD) have an increased risk of dementia, yet patients and clinicians frequently avoid talking about it due to associated stigma, and the perception that "nothing can be done about it". However, open conversations about PD dementia may allow people with the condition to access treatment and support, and may increase participation in research aimed at understanding PD dementia. OBJECTIVES: To co-produce information resources for patients and healthcare professionals to improve conversations about PD dementia. METHODS: We worked with people with PD, engagement experts, artists, and a PD charity to open up these conversations. 34 participants (16 PD; 6 PD dementia; 1 Parkinsonism, 11 caregivers) attended creative workshops to examine fears about PD dementia and develop information resources. 25 PD experts contributed to the resources. RESULTS: While most people with PD (70%) and caregivers (81%) shared worries about cognitive changes prior to the workshops, only 38% and 30%, respectively, had raised these concerns with a healthcare professional. 91% of people with PD and 73% of caregivers agreed that PD clinicians should ask about cognitive changes routinely through direct questions and perform cognitive tests at clinic appointments. We used insights from the creative workshops, and input from a network of PD experts to co-develop two open-access resources: one for people with PD and their families, and one for healthcare professionals. CONCLUSION: Using artistic and creative workshops, co-learning and striving for diverse voices, we co-produced relevant resources for a wider audience to improve conversations about PD dementia.

Foreign accent syndrome and other neuropsychological sequelae of a parieto-occipital lesion following COVID-19 associated posterior reversible encephalopathy syndrome.

OBJECTIVE: We describe a previously fit and well 54-year-old female who acquired a range of severe and persisting neuropsychological impairments following a posterior reversible encephalopathy syndrome (PRES) complication of COVID-19. The initial presentation included aphasia, a neurogenic foreign accent syndrome (FAS) and a persisting complete cortical blindness from the underpinning parieto-occipital brain injury. METHOD: Neuropsychological single clinical case report. RESULTS: The patient retained insight and made good early progress with their adjustment to the numerous losses caused by the COVID-19 associated acquired brain injury. Comprehensive neuropsychological investigation characterised an acalculia, along with deficits in focused, sustained and divided attention impacting on verbal memory, working memory and executive functioning, amongst numerous relative strengths. CONCLUSION: Similar to PRES from other aetiologies, COVID-19 associated PRES can in some cases cause irreversible acquired brain injury. The diverse neuropsychological effects need to be comprehensively investigated and managed. This case adds to the neuropsychological literature on PRES, FAS and acquired brain injury as a rare complication of SARS-CoV-2.

Spatial attention and spatial short term memory in PSP and Parkinson's disease.

Progressive Supranuclear Palsy (PSP) is a neurodegenerative disorder characterised by deterioration in motor, oculomotor and cognitive function. A key clinical feature of PSP is the progressive paralysis of eye movements, most notably for vertical saccades. These oculomotor signs can be subtle, however, and PSP is often misdiagnosed as Parkinson's disease (PD), in its early stages. Although some of the clinical features of PD and PSP overlap, they are distinct disorders with differing underlying pathological processes, responses to treatment and prognoses. One key difference lies in the effects the diseases have on cognition. The oculomotor system is tightly linked to cognitive processes such as spatial attention and spatial short-term memory (sSTM), and previous studies have suggested that PSP and PD experience different deficits in these domains. We therefore hypothesised that people with PSP (N = 15) would experience problems with attention (assessed with feature and conjunction visual search tasks) and sSTM (assessed with the Corsi blocks task) compared to people with PD (N = 16) and Age Matched Controls (N = 15). As predicted, feature and conjunction search were sgnificantly slower in the PSP group compared to the other groups, and this deficit was significantly worse for feature compared to conjunction search. The PD group did not differ from AMC on feature search but were significantly impaired on the conjunction search. The PSP group also had a pronounced vertical sSTM impairment that was not present in PD or AMC groups. It is argued that PSP is associated with specific impairment of visuospatial cognition which is caused by degeneration of the oculomotor structures that support exogenous spatial attention, consistent with oculomotor theories of spatial attention and memory.

Persistent Cortical Blindness Following Posterior Reversible Encephalopathy Syndrome (PRES) as a Complication of COVID-19 Pneumonia.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic emerged in China in December 2019. Since then, there have been growing reports of coronavirus disease 2019 (COVID-19) cases with neurological involvement. We present a case of a 54-year-old woman who presented with confirmed SARS-CoV-2 pneumonia, complicated by a prolonged intensive care stay and posterior reversible encephalopathy syndrome (PRES). This resulted in persistent cortical blindness (Anton's syndrome). PRES has only rarely been reported in relation to SARS-CoV-2 infection and no patients have developed persistent cortical blindness. We summarise the clinical presentation of the patient and review the current literature.

Spatial working memory in Progressive Supranuclear Palsy.

The neural and cognitive mechanisms of spatial working memory are tightly coupled with the systems that control eye-movements but the precise nature of this coupling is not well understood. In particular, there are very few neuropsychological studies that explicitly examine how deficits of oculomotor control affect visuospatial working memory. Here, we examined the link between spatial working memory and the oculomotor system in a sample of patients with Progressive Supranuclear Palsy, a degenerative neurological disease characterised by defective vertical eye-movements but relatively preserved horizontal eye-movements. Consistent with the idea that the oculomotor system plays a critical role in spatial working memory performance, people with PSP had significantly shorter spatial spans when stimuli were presented along the vertical axis compared to the horizontal axis. This effect was not observed in age matched controls. We hypothesise that PSP disrupts a colliculo-parietal feedback loop that contributes to the maintenance of activation in a parietal priority map during the delay period. This result is the first direct neuropsychological evidence for an association between oculomotor function and spatial working memory and is broadly consistent with idea that rehearsal in visuospatial working memory is mediated by an 'oculomotor loop', as proposed by Baddeley (1986). We conclude that optimal spatial working memory performance depends on an intact oculomotor system.

Visual Search in Progressive Supranuclear Palsy.

Progressive supranuclear palsy is often considered a disease of the motor system and is characterised by a profound oculomotor impairment. The oculomotor system is also known to be fundamentally important in cognitive processes such as attention and working memory, but the way in which these functions are affected by PSP is not well understood. In this chapter we outline the pathology and typical presentation of PSP, with a focus on the oculomotor impairment, briefly outline the role of the oculomotor system in spatial cognition and discuss some key studies examining spatial attention and memory in PSP. We then present new data from a study that specifically examined the effect of PSP on visual search. Our results demonstrated a profound impairment of visual search which is most severe for feature search along the vertical axis. These findings are interpreted with respect to the biased-competition theory of attention, and we discuss possible clinical applications of our results.

Visual Hallucinations in Eye Disease and Lewy Body Disease.

OBJECTIVES: Visual hallucinations (VH) most commonly occur in eye disease (ED), Parkinson disease (PD), and Lewy body dementia (LBD). The phenomenology of VH is likely to carry important information about the brain areas within the visual system generating them. METHODS: Data from five controlled cross-sectional VH studies (164 controls, 135 ED, 156 PD, 79 [PDD 48 + DLB 31] LBD) were combined and analyzed. The prevalence, phenomenology, frequency, duration, and contents of VH were compared across diseases and sex. RESULTS: Simple VH were most common in ED patients (ED 65% versus LBD 22% versus PD 9%, χ(2) = 31.43, df = 2, p < 0.001), whereas complex VH were more common in LBD (LBD 76% versus ED 38%, versus PD 28%, χ(2) = 96.80, df = 2, p < 0.001). The phenomenology of complex VH was different across diseases and sex. ED patients reported more "flowers" (ED 21% versus LBD 6% versus PD 0%, χ(2) = 10.04, df = 2, p = 0.005) and "body parts" (ED 40% versus LBD 17% versus PD 13%, χ(2) = 11.14, df = 2, p = 0.004); in contrast, LBD patients reported "people" (LBD 85% versus ED 67% versus PD 63%, χ(2) = 6.20, df = 2, p = 0.045) and "animals/insects" (LBD 50% versus PD 42% versus ED 21%, χ(2) = 9.76, df = 2, p = 0.008). Men reported more "machines" (13% versus 2%, χ(2) = 6.94, df = 1, p = 0.008), whereas women reported more "family members/children" (48% versus 29%, χ(2) = 5.10, df = 1, p = 0.024). CONCLUSIONS: The phenomenology of VH is likely related to disease-specific dysfunctions within the visual system and to past, personal experiences.

Visual exploration in Parkinson's disease and Parkinson's disease dementia.

Parkinson's disease, typically thought of as a movement disorder, is increasingly recognized as causing cognitive impairment and dementia. Eye movement abnormalities are also described, including impairment of rapid eye movements (saccades) and the fixations interspersed between them. Such movements are under the influence of cortical and subcortical networks commonly targeted by the neurodegeneration seen in Parkinson's disease and, as such, may provide a marker for cognitive decline. This study examined the error rates and visual exploration strategies of subjects with Parkinson's disease, with and without cognitive impairment, whilst performing a battery of visuo-cognitive tasks. Error rates were significantly higher in those Parkinson's disease groups with either mild cognitive impairment (P = 0.001) or dementia (P < 0.001), than in cognitively normal subjects with Parkinson's disease. When compared with cognitively normal subjects with Parkinson's disease, exploration strategy, as measured by a number of eye tracking variables, was least efficient in the dementia group but was also affected in those subjects with Parkinson's disease with mild cognitive impairment. When compared with control subjects and cognitively normal subjects with Parkinson's disease, saccade amplitudes were significantly reduced in the groups with mild cognitive impairment or dementia. Fixation duration was longer in all Parkinson's disease groups compared with healthy control subjects but was longest for cognitively impaired Parkinson's disease groups. The strongest predictor of average fixation duration was disease severity. Analysing only data from the most complex task, with the highest error rates, both cognitive impairment and disease severity contributed to a predictive model for fixation duration [F(2,76) = 12.52, P ≤ 0.001], but medication dose did not (r = 0.18, n = 78, P = 0.098, not significant). This study highlights the potential use of exploration strategy measures as a marker of cognitive decline in Parkinson's disease and reveals the efficiency by which fixations and saccades are deployed in the build-up to a cognitive response, rather than merely focusing on the outcome itself. The prolongation of fixation duration, present to a small but significant degree even in cognitively normal subjects with Parkinson's disease, suggests a disease-specific impact on the networks directing visual exploration, although the study also highlights the multi-factorial nature of changes in exploration and the significant impact of cognitive decline on efficiency of visual search.

Neurorehabilitation in Parkinson disease.

Parkinson disease (PD) is the second commonest neurodegenerative disorder in the UK with an increasing prevalence in our aging population. The clinical features of PD are varied with a variety of "motor" and "nonmotor" symptoms and the condition is best thought of as a multisystem neurodegenerative disorder rather than as a "pure" movement disorder. Although the mainstay of treatment is pharmacological, nonpharmacological interventions are vital as part of a multidisciplinary approach to the disorder. Neurorehabilitative interventions have been used for some time in the treatment of PD but, until recently, there has been little evidence to support the clinical impression that physiotherapy, occupational therapy, and speech and language therapy have a positive impact on both motor and nonmotor symptoms. This chapter will review the current evidence base for neurorehabilitation in PD and discuss the challenges of service provision within healthcare systems.

Visual sampling during walking in people with Parkinson's disease and the influence of environment and dual-task.

Visuospatial dysfunction may play a crucial role in gait disturbance in Parkinson's disease (PD), in particular how visual exploration of the environment is integrated into gait control. In this study, we tested the hypothesis that people with PD would visually sample their environment less frequently than controls when walking under different levels of environmental complexity and dual-task. We also explored associations between saccadic outcomes and clinical measures. Visual sampling (saccadic frequency) and gait were measured concurrently for 21 people with PD and 12 age-matched controls during a series of walking tasks using electrooculography (EOG) synchronised with 3D motion analysis (VICON). Participants walked under four environmental conditions during single and dual-task. Saccade frequency and task duration were measured. PD participants took longer to complete all tasks than controls (p =.004). Environment and dual-task impacted on saccadic frequency especially for PD. For both groups, saccadic frequency increased when approaching a turn compared with straight walking. Prior to turning, PD made less frequent early preparatory saccades than controls (p =.012). Under dual-task conditions, people with PD made less frequent saccades than controls when walking straight ahead (p =.040) and in preparation for a turn (p =.032). Increased saccadic frequency was related to poorer attention, cognition and spatial memory in controls and people with PD for single-task conditions but not dual-task conditions. Impaired visual sampling may contribute to the gait disorder in PD, especially when navigating through complex environments and when distracted.

Dorsal rather than ventral visual pathways discriminate freezing status in Parkinson's disease.

BACKGROUND: Although visuospatial deficits have been linked with freezing of gait (FOG) in Parkinson's disease (PD), the specific effects of dorsal and ventral visual pathway dysfunction on FOG is not well understood. METHOD: We assessed visuospatial function in FOG using an angle discrimination test (dorsal visual pathway bias) and overlapping figure test (ventral visual pathway bias), and recorded overall response time, mean fixation duration and dwell time. Covariate analysis was conducted controlling for disease duration, motor severity, contrast sensitivity and attention with Bonferroni adjustments for multiple comparisons. RESULTS: Twenty seven people with FOG, 27 people without FOG and 24 controls were assessed. Average fixation duration during angle discrimination distinguished freezing status: [F (1, 43) = 4.77 p < 0.05] (1-way ANCOVA). CONCLUSION: Results indicate a preferential dysfunction of dorsal occipito-parietal pathways in FOG, independent of disease severity, attentional deficit, and contrast sensitivity.

Neuro-Sweet's disease.

Sweet's syndrome, or acute febrile neutrophilic dermatosis, is a multisystem, inflammatory disease characterised by tender skin lesions and neutrophilic infiltration of various organs, including the nervous system. A rare condition, neuro-Sweet's can present with a wide variety of neurological symptoms dependent on the region of the CNS affected. Here we present a case of neuro-Sweet's disease in association with Crohn's disease.

Visual symptoms in Parkinson's disease and Parkinson's disease dementia.

Visual symptoms are common in PD and PD dementia and include difficulty reading, double vision, illusions, feelings of presence and passage, and complex visual hallucinations. Despite the established prognostic implications of complex visual hallucinations, the interaction between cognitive decline, visual impairment, and other visual symptoms remains poorly understood. Our aim was to characterize the spectrum of visual symptomatology in PD and examine clinical predictors for their occurrence. Sixty-four subjects with PD, 26 with PD dementia, and 32 age-matched controls were assessed for visual symptoms, cognitive impairment, and ocular pathology. Complex visual hallucinations were common in PD (17%) and PD dementia (89%). Dementia subjects reported illusions (65%) and presence (62%) more frequently than PD or control subjects, but the frequency of passage hallucinations in PD and PD dementia groups was equivalent (48% versus 69%, respectively; P = 0.102). Visual acuity and contrast sensitivity was impaired in parkinsonian subjects, with disease severity and age emerging as the key predictors. Regression analysis identified a variety of factors independently predictive of complex visual hallucinations (e.g., dementia, visual acuity, and depression), illusions (e.g., excessive daytime somnolence and disease severity), and presence (e.g., rapid eye movement sleep behavior disorder and excessive daytime somnolence). Our results demonstrate that different "hallucinatory" experiences in PD do not necessarily share common disease predictors and may, therefore, be driven by different pathophysiological mechanisms. If confirmed, such a finding will have important implications for future studies of visual symptoms and cognitive decline in PD and PD dementia.

Two in the hand, an essential lesson in tremor management.

Dopa responsive dystonia results from abnormalities in the dopamine synthesis pathway which produces an array of phenotypic presentations with equally numerous genotypes. First documented in children in 1971, the 'classic' phenotype is childhood onset, predominantly lower limb dystonia which gradually progresses to generalised dystonia. Other hallmarks of 'classical' dopa responsive dystonia include marked diurnal variation in symptom severity (worse in the evening), subsequent development of parkinsonism and an excellent, sustained response to levodopa. More recently, adult onset variants have been reported. Here we discuss two siblings with dopa responsive dystonia caused by a mutation in the GTP cyclohydrolase 1 gene. Both presented in adulthood with tremor rather than the 'classic' phenotype. A video is presented (available online) followed by a brief discussion of the literature.

The retina in Parkinson's disease.

As a more complete picture of the clinical phenotype of Parkinson's disease emerges, non-motor symptoms have become increasingly studied. Prominent among these non-motor phenomena are mood disturbance, cognitive decline and dementia, sleep disorders, hyposmia and autonomic failure. In addition, visual symptoms are common, ranging from complaints of dry eyes and reading difficulties, through to perceptual disturbances (feelings of presence and passage) and complex visual hallucinations. Such visual symptoms are a considerable cause of morbidity in Parkinson's disease and, with respect to visual hallucinations, are an important predictor of cognitive decline as well as institutional care and mortality. Evidence exists of visual dysfunction at several levels of the visual pathway in Parkinson's disease. This includes psychophysical, electrophysiological and morphological evidence of disruption of retinal structure and function, in addition to disorders of 'higher' (cortical) visual processing. In this review, we will draw together work from animal and human studies in an attempt to provide an insight into how Parkinson's disease affects the retina and how these changes might contribute to the visual symptoms experienced by patients.

Carbamazepine-induced interstitial pneumonitis in a lung transplant patient.

A 19-year-old female lung transplant recipient developed peripheral eosinophilia and interstitial infiltrates on chest radiograph shortly after commencing carbamazepine. A lung biopsy was consistent with interstitial pneumonitis and following withdrawal of the drug and treatment with steroids her symptoms resolved. This is the first described case of carbamezipine-induced pneumonitis in the lung transplant population.