Eye movement problems and differential diagnosis of the parkinsonian syndromes

Differential clinical diagnosis of the parkinsonian syndromes, viz., Parkinson’s disease (PD), progressive supranuclear palsy (PSP), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA) can be difficult. Eye movement problems, however, are a chronic complication of many of these disorders and may be a useful aid to diagnosis. Hence, the presence in PSP of vertical supranuclear gaze palsy, fixation instability, lid retraction, blepharospasm, and apraxia of eyelid opening and closing is useful in separating PD from PSP. Moreover, atypical features of PSP include slowing of upward saccades, moderate slowing of downward saccades, the presence of a full range of voluntary vertical eye movements, a curved trajectory of oblique saccades, and absence of square-wave jerks. Downgaze palsy is probably the most useful diagnostic clinical symptom of PSP. By contrast, DLB patients are specifically impaired in both reflexive and saccadic execution and in the performance of more complex saccadic eye movement tasks. Problems in convergence in DLB are also followed by akinesia and rigidity. Abnormal ocular fixation may occur in a significant proportion of MSA patients along with excessive square-wave jerks, a mild supranuclear gaze palsy, a gaze-evoked nystagmus, a positioning down-beat nystagmus, mild-moderate saccadic hypometria, impaired smooth pursuit movements, and reduced vestibulo-ocular reflex (VOR) suppression. There may be considerable overlap between the eye movement problems characteristic of the various parkinsonian disorders, but taken together with other signs and symptoms, can be a useful aid in differential diagnosis, especially in the separation of PD and PSP.

Neurophysiological investigations for the diagnosis of non-epileptic attack disorder in neuropsychiatry services:from safety standards to improved effectiveness

OBJECTIVE: The discipline of clinical neuropsychiatry currently provides specialised services for a number of conditions that cross the traditional boundaries of neurology and psychiatry, including non-epileptic attack disorder. Neurophysiological investigations have an important role within neuropsychiatry services, with video-electroencephalography (EEG) telemetry being the gold standard investigation for the differential diagnosis between epileptic seizures and non-epileptic attacks. This article reviews existing evidence on best practices for neurophysiology investigations, with focus on safety measures for video-EEG telemetry. METHODS: We conducted a systematic literature review using the PubMed database in order to identify the scientific literature on the best practices when using neurophysiological investigations in patients with suspected epileptic seizures or non-epileptic attacks. RESULTS: Specific measures need to be implemented for video-EEG telemetry to be safely and effectively carried out by neuropsychiatry services. A confirmed diagnosis of non-epileptic attack disorder following video-EEG telemetry carried out within neuropsychiatry units has the inherent advantage of allowing diagnosis communication and implementation of treatment strategies in a timely fashion, potentially improving clinical outcomes and cost-effectiveness significantly. CONCLUSION: The identified recommendations set the stage for the development of standardised guidelines to enable neuropsychiatry services to implement streamlined and evidence-based care pathways.

Ophthalmological manifestations of multiple sclerosis

Optic neuritis, as a result of the formation of demyelination plaques in the optic nerve, is one of the commonest early symptoms of multiple sclerosis. Hence, it is important that optometrists are aware of the symptoms of optic neuritis and of the conditions with which it can be confused. However, only a proportion of patients with optic neuritis will develop the symptoms of multiple sclerosis. The first part of the article describes the symptoms and differential diagnosis of optic neuritis and its relationship with multiple sclerosis. In the second part of the article, the variety of visual changes and symptoms which can be observed in multiple sclerosis patients will be described.

Progressive supranuclear palsy (PSP): general pathology and visual signs and symptoms

Progressive supranuclear palsy (PSP) is a rare, degenerative disorder of the brain believed to affect between 1.39 and 6.6 individuals per 100,000 of the population. The disorder is likely to be more common than suggested by these data due to difficulties in diagnosis and especially in distinguishing PSP from other conditions with similar symptoms such as multiple system atrophy (MSA), corticobasal degeneration (CBD), and Parkinson’s disease (PD). PSP was first described in 1964 by Steele, Richardson and Olszewski and originally called Steele-Richardson-Olszewski syndrome. The disorder is the second commonest syndrome in which the patient exhibits ‘parkinsonism’, viz., a range of problems involving movement most typically manifest in PD itself but also seen in PSP, MSA and CBD. Although primarily a brain disorder, patients with PSP exhibit a range of visual clinical signs and symptoms that may be useful in differential diagnosis. Hence, the present article describes the general clinical and pathological features of PSP, its specific visual signs and symptoms, discusses the usefulness of these signs in differential diagnosis, and considers the various treatment options.

General features of Multiple System Atrophy

Multiple system atrophy (MSA) is a rare movement disorder and a member of a group of neurodegenerative diseases referred to collectively as the ‘parkinsonian syndromes’. Characteristic of these syndromes is that the patient exhibits symptoms of ‘parkinsonism’, viz., a range of problems involving movement, most typically manifest in Parkinson’s disease (PD) itself1, but also seen in progressive supranuclear palsy (PSP), and to some extent in dementia with Lewy bodies (DLB). MSA is a relatively ‘new’ descriptive term and is derived from three previously described diseases, viz., olivopontocerebellar atrophy, striato-nigral degeneration, and Shy-Drager syndrome. The classical symptoms of MSA include parkinsonism, ataxia, and autonomic dysfunction.6 Ataxia describes a gross lack of coordination of muscle movements while autonomic dysfunction involves a variety of systems that regulate unconscious bodily functions such as heart rate, blood pressure, bladder function, and digestion. Although primarily a neurological disorder, patients with MSA may also develop visual signs and symptoms that could be useful in differential diagnosis. The most important visual signs may include oculomotor dysfunction and problems in pupil reactivity but are less likely to involve aspects of primary vision such as visual acuity, colour vision, and visual fields. In addition, the eye-care practitioner can contribute to the management of the visual problems of MSA and therefore, help to improve quality of life of the patient. Hence, this first article in a two-part series describes the general features of MSA including its prevalence, signs and symptoms, diagnosis, pathology, and possible causes.

Visual signs and symptoms of Multiple System Atrophy

Multiple system atrophy (MSA) is a rare movement disorder and a member of a group of neurodegenerative diseases, which include Parkinson’s disease (PD) and progressive supranuclear palsy (PSP), and referred to as the ‘parkinsonian syndromes’. Although primarily a neurological disorder, patients with MSA may also develop visual signs and symptoms that could be useful in differential diagnosis. In addition, the eye-care practitioner may contribute to the management of visual problems of MSA patients and therefore, help to improve quality of life. This second article in the series considers the visual signs and symptoms of MSA with special reference to those features most useful in differential diagnosis of the parkinsonian syndromes.

Oculo-visual dysfunction in Parkinson's disease

This review describes the oculo-visual problems likely to be encountered in Parkinson's disease (PD) with special reference to three questions: (1) are there visual symptoms characteristic of the prodromal phase of PD, (2) is PD dementia associated with specific visual changes, and (3) can visual symptoms help in the differential diagnosis of the parkinsonian syndromes, viz. PD, progressive supranuclear palsy (PSP), dementia with Lewy bodies (DLB), multiple system atrophy (MSA), and corticobasal degeneration (CBD)? Oculo-visual dysfunction in PD can involve visual acuity, dynamic contrast sensitivity, colour discrimination, pupil reactivity, eye movement, motion perception, and visual processing speeds. In addition, disturbance of visuo-spatial orientation, facial recognition problems, and chronic visual hallucinations may be present. Prodromal features of PD may include autonomic system dysfunction potentially affecting pupil reactivity, abnormal colour vision, abnormal stereopsis associated with postural instability, defects in smooth pursuit eye movements, and deficits in visuo-motor adaptation, especially when accompanied by idiopathic rapid eye movement (REM) sleep behaviour disorder. PD dementia is associated with the exacerbation of many oculo-visual problems but those involving eye movements, visuo-spatial function, and visual hallucinations are most characteristic. Useful diagnostic features in differentiating the parkinsonian symptoms are the presence of visual hallucinations, visuo-spatial problems, and variation in saccadic eye movement dysfunction.

Visual signs and symptoms of multiple system atrophy

Multiple system atrophy (MSA) is a rare movement disorder and a member of the 'parkinsonian syndromes', which also include Parkinson's disease (PD), progressive supranuclear palsy (PSP), dementia with Lewy bodies (DLB) and corticobasal degeneration (CBD). Multiple system atrophy is a complex syndrome, in which patients exhibit a variety of signs and symptoms, including parkinsonism, ataxia and autonomic dysfunction. It can be difficult to separate MSA from the other parkinsonian syndromes but if ocular signs and symptoms are present, they may aid differential diagnosis. Typical ocular features of MSA include blepharospasm, excessive square-wave jerks, mild to moderate hypometria of saccades, impaired vestibular-ocular reflex (VOR), nystagmus and impaired event-related evoked potentials. Less typical features include slowing of saccadic eye movements, the presence of vertical gaze palsy, visual hallucinations and an impaired electroretinogram (ERG). Aspects of primary vision such as visual acuity, colour vision or visual fields are usually unaffected. Management of the disease to deal with problems of walking, movement, daily tasks and speech problems is important in MSA. Optometrists can work in collaboration with the patient and health-care providers to identify and manage the patient's visual deficits. A more specific role for the optometrist is to correct vision to prevent falls and to monitor the anterior eye to prevent dry eye and control blepharospasm.

Dementia with Lewy bodies

Dementia with Lewy bodies (‘Lewy body dementia' or ‘diffuse Lewy body disease') (DLB) is the second commonest form of dementia after Alzheimer’s disease (AD). Characteristic of DLB are: (1) fluctuating cognitive ability with variations in attention and alertness, (2) recurrent visual hallucinations, and (3) motor features including akinesia, rigidity, and tremor. Various brain regions are affected in DLD including cortical and limbic regions. Histopathologically, alpha-synuclein-immunoreactive Lewy bodies (LB) are observed in the substantia nigra and in the cerebral cortex. DLB has affinities both with the parkinsonian syndromes including Parkinson’s disease (PD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and multiple system atrophy (MSA), and with AD, which can make differential diagnosis difficult. The presence of visual hallucinations may aid differential diagnosis of the parkinsononian syndromes and occipital hypometabolism may be a useful potential method of distinguishing DLB from AD. Treatment of CBD involves managing and reducing the effect of symptoms.

History and symptom taking in contact lens fitting and aftercare

Aim: To appraise history and symptom taking for contact lens consultations, to determine current practice and to make recommendations for best practice. Method: The peer reviewed academic literature was reviewed and the results informed a survey completed by 256 eye care practitioners (ECPs) on their current practice and influences. Results: The last eye-test date, last contact lens aftercare (for existing wearers) and reason for visit are key questions for most ECPs. Detailed use of contact lens questions are more commonly applied in aftercares than when refitting patients who have previously discontinued wear (87% vs 56% use), whereas questions on ocular and general history, medication and lifestyle were generally more commonly utilised for new patients than in aftercares (72% vs 50%). 75% of ECPs requested patients bring a list of their medication to appointments. Differential diagnosis questioning was thorough in most ECPs (87% of relevant questions asked). Attempts to optimise compliance included oral instruction (95% always) and written patient instructions (95% at least sometimes). Abbreviations were used by 39% of respondents (26% used ones provided by a professional body). Conclusion: There is scope for more consistency in history and symptom taking for contact lens consultations and recommendations are made.

CLAE to move to online format

Editorial: The 2015 BCLA annual conference was another fantastic affair. It was the first time the conference was held in the beautiful city of Liverpool. The venue was great and the programme was excellent. The venue overlooked the River Mersey and many of the hotels were local boutique hotels. I stayed in one which was formerly the offices of White Star Liners—where the RMS Titanic was originally registered. The hotel decor was consistent with its historic significance. The BCLA gala dinner was held in the hugely impressive Anglican Cathedral with entertainment from a Beatles tribute band. That will certainly be a hard act to follow at the next conference in 2017. Brian Tompkins took the reigns as the new BCLA president. Professor Fiona Stapleton was the recipient of the BCLA Gold Medal Award. The winner of the poster competition was Dorota Szczesna-Iskander with a poster entitled ‘Dry Contact lens poor wettability and visual performance’. Second place was Renee Reeder with her poster entitled ‘Abnormal Rosacea as a differential diagnosis in corneal scarring’. And third place was Maria Jesus Gonzalez-Garcia with her poster entitled ‘Dry Effect of the Environmental Conditions on Tear Inflammatory Mediators Concentration in Contact Lens Wearers’. The photographic competition winner was Professor Wolfgang Sickenberger from Jena in Germany. The Editorial Panel of CLAE met at the BCLA conference for their first biannual meeting. The journal metrics were discussed. In terms of number of submissions of new papers CLAE seems to have plateaued after seeing a rapid growth in the number of submissions over the last few years. The increase over the last few years could be attributed to the fact that CLAE was awarded an impact factor for the first time in 2012. This year it seems that impact factors across nearly all ophthalmic related journals has dropped. This could in part be due to the fact that last year was a ‘Research Exercise Framework (REF) year for UK universities, where they are judged on quality of their research output. The next REF is in 2020 so we may see changes nearing that time. Looking at article downloads, there seems to be a continued rise in figures. Currently CLAE attracts around 85,000 downloads per year (this is an increase of around 10,000 per year for the last few years) and the 2015 prediction is 120,000! With this in mind and with other contributing factors too, the BCLA has decided to move to online delivery of CLAE to its members starting from issue 5 of 2015. Some members do like to flick through the pages of a hard copy of the journal so members will still have the option of receiving a hard copy through the post but the default journal delivery method will now be online. The BCLA office will send various alerts and content details to members email addresses. To access CLAE online you will need to log in via the BCLA web page, currently you then click on ‘Resources’ and then under ‘Free and Discounted Publications’ you will see CLAE. This actually takes you to CLAE’s own webpage (www.contactlensjournal.com) but you need to log in via the BCLA web page. The BCLA plans to change these weblinks so that from the BCLA web page you can link to the journal website much more easily and you have the choice of going directly into the general website for CLAE or straight to the current issue. In 2016 you will see an even easier way of accessing CLAE online as the BCLA will launch a CLAE application for mobile devices where the journal can be downloaded as a ‘flick-book’. This is a great way of bringing CLAE into the modern era where people access their information in newer ways. For many the BCLA conference was part of a very busy conference week as it was preceded by the International Association of Contact Lens Educators’ (IACLE) Third World Congress, held in Manchester on the 4 days before the BCLA conference. The first and second IACE World Congresses were held in Waterloo, Canada in 1994 and 2000 respectively and hosted by Professor Des Fonn. Professor Fonn was the recipient of the first ever IACLE lifetime achievement award. The Third IACLE World Congress saw more than 100 contact lens educators and industry representatives from around 30 countries gather in the UK for the four-day event, hosted by The University of Manchester. Delegates gained hands-on experience of innovations in teaching, such as learning delivery systems, the use of iPads in the classroom and for creating ePub content, and augmented and virtual reality technologies. IACLE members around the world also took part via a live online broadcast. The Third IACLE World Congress was made possible by the generous support of Sponsors Alcon, CooperVision and Johnson & Johnson Vision Care., for more information look at the IACLE web page (www.iacle.org).

Cognitive processing in non-communicative patients:what can event-related potentials tell us?

Event-related potentials (ERP) have been proposed to improve the differential diagnosis of non-responsive patients. We investigated the potential of the P300 as a reliable marker of conscious processing in patients with locked-in syndrome (LIS). Eleven chronic LIS patients and 10 healthy subjects (HS) listened to a complex-tone auditory oddball paradigm, first in a passive condition (listen to the sounds) and then in an active condition (counting the deviant tones). Seven out of nine HS displayed a P300 waveform in the passive condition and all in the active condition. HS showed statistically significant changes in peak and area amplitude between conditions. Three out of seven LIS patients showed the P3 waveform in the passive condition and five of seven in the active condition. No changes in peak amplitude and only a significant difference at one electrode in area amplitude were observed in this group between conditions. We conclude that, in spite of keeping full consciousness and intact or nearly intact cortical functions, compared to HS, LIS patients present less reliable results when testing with ERP, specifically in the passive condition. We thus strongly recommend applying ERP paradigms in an active condition when evaluating consciousness in non-responsive patients.

A study of potential serum markers for a diagnosis of gram-positive and gram-negative bacterial sepsis

Sepsis continues to be a major cause of morbidity and mortality as it can readily lead tosevere sepsis, septic shock, multiple organ failure and death. The onset can be rapid and difficult to define clinically. Despite the numerous candidate markers proposed in the literature, to date a serum marker for sepsis has not been found. The aim of this study was to assay the serum of clinically diagnosed patients with eithera Gram-negative or Gram- positive bacterial sepsis for elevated levels of nine potentialmarkers of sepsis, using commercially produced enzyme linked immunosorbent assays(ELISA). The purpose was to find a test marker for sepsis that would be helpful toclinicians in cases of uncertain sepsis and consequently expose false positive BC'scaused by skin or environmental contaminants. Nine test markers were assayed including IL-6, IL-I 0, ILI2, TNF-α, lipopolysaccharide binding protein, procalcitonin, sE-selectin, sICAM -1 and a potential differential marker for Gram-positive sepsis- anti-lipid S antibody. A total of 445 patients were enrolled into this study from the Queen Elizabeth Hospital and Selly Oak Hospital (Birmingham). The results showed that all the markers were elevated in patients with sepsis and that patients with a Gram-negative sepsis consistently produced higher median/range serum levels than those with a Gram-positive sepsis. No single marker was able to identify all the septic patients. Combining two markers caused the sensitivities and specificities for a diagnosis of sepsis to increase to within a 90% to 100% range. By a process of elimination the markers that survived into the last phase were IL-6 with sICAM -1, and anti-lipid S IgG assays Defining cut-off levels for a diagnosis of sepsis became problematic and a semi-blind trial was devised to test the markers in the absence of both clinical details and positive blood cultures. Patients with pyrexia of unknown origin and negative BC were included in this phase (4). The results showed that IL-6 with sICAM-l are authentic markers of sepsis. There was 82% agreement between the test marker diagnosis and the clinical diagnosis for sepsis in patients with a Gram-positive BC and 78% agreement in cases of Gram-negative Be. In the PUO group the test markers identified 12 cases of sepsis and the clinical diagnosis 15. The markers were shown to differentiate between early sepsis and sepsis, inflammatory responses and infection. Anti-lipid S with IL-6 proved be a sensitive marker for Gram-positive infections/sepsis.