Health at the writing desk of John Ruskin: a study of handwriting and illness.

Though John Ruskin (1819-1900) is remembered principally for his work as a theorist, art critic and historian of visual culture, he wrote exhaustively about his health in his correspondence and diaries. Ruskin was prone to recurring depressive and hypochondriacal feelings in his youth and adulthood. In 1871, at the age of 52 years, he developed an illness with relapsing psychiatric and neurological features. He had a series of attacks of brain disturbance, and a deterioration of his mental faculties affected his writing for years before curtailing his career a decade before he died. Previous writers have suggested he had a psychiatric malady, perhaps schizophrenia or schizoaffective disorder. But the more obvious conclusion from a close medical reading of Ruskin's descriptions of his illness is he had some sort of 'organic' brain illness. This paper aims to give insight into the relationship between Ruskin's state of well-being and the features of his writing through a palaeographical study of his letters and diary entries. We examine the handwriting for physical traces of Ruskin's major brain illness, guided by the historical narrative of the illness. We also examine Ruskin's recording of his experiences for what they reveal about the failure of his health and its impact on his work. Ruskin's handwriting does not have clear-cut pathological features before around 1885, though suggestions of subtle writing deficits were present as early as 1876. After 1887, Ruskin's handwriting shows fixed pathological signs-tremor, disturbed letter formation and features that reflect a slow and laborious process of writing. These observations are more than could be explained by normal ageing, and suggest the presence of a neurological deficit affecting writing control. Our findings are consistent with conclusions that we drew from the historical record-that John Ruskin had an organic neurological disorder with cognitive, behavioural, psychiatric and motor effects.

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.

Functional dystonia and the borderland between neurology and psychiatry: New concepts.

Mind-brain dualism has dominated historical commentary on dystonia, a dichotomous approach that has left our conceptual grasp of it stubbornly incomplete. This is particularly true of functional dystonia, most diagnostically challenging of all functional movement disorders, in which the question of inherent psychogenicity remains a focus of debate. Phenomenological signs considered in isolation lack the specificity to distinguish organic and nonorganic forms, and dystonia's variability has frustrated attempts to develop objective laboratory-supported standards. Diagnostic criteria for functional dystonia that place emphasis on psychiatric symptoms perform poorly in studies of reliability, partly explained by the high frequency of psychopathology in organic dystonia. Novel approaches from the cognitive neurosciences may offer a way forward. Theory on Bayesian statistical prediction in cognitive processing is supported by sufficient experimental evidence for this model to be taken seriously as a way of reconciling contradictory notions about voluntary and unconscious motor control in functional movement disorders. In a Bayesian formulation of functional dystonia, misallocation of attention and abnormal predictive beliefs generate movements that are executed without a sense of agency. Building on this framework, there is a consensus that a biopsychosocial approach is required and that a unified philosophy of brain and mind is the best way to locate dystonia in the neurology-psychiatry borderland. At a practical level, movement disorder neurologists are best placed to differentiate organic from functional dystonia. The main role of psychiatrists is in the diagnosis and management of the primarily psychiatric disorders that often accompany dystonia. © 2016 International Parkinson and Movement Disorder Society.

Study of levodopa response in Parkinson's disease: Observations on rates of motor progression.

INTRODUCTION: It is important to understand how the rate of motor progression in PD relates to dopaminergic treatment. METHODS: The methods for this study comprised prospective defined off state measurements of the levodopa response at 3-year intervals over a mean 13.3-year period in 34 patients enrolled before treatment initiation. RESULTS: Despite worsening of on and off scores, the magnitude of the l-dopa short-duration response is maintained as the disease progresses. A linear mixed-effects regression analysis of off phase motor scores showed a yearly deterioration of 2.3% of the maximum disability score. Greater motor disability at the commencement of treatment was an independent predictor of faster progression. Demented patients had worse motor function than those without dementia (P = 0.02), and motor deficit appeared to accelerate toward the end of the disease course in patients who had died. CONCLUSIONS: These observations should inform clinical trial design for drugs with possible neuroprotective properties.

Posterior Reversible Encephalopathy Syndrome and Subarachnoid Hemorrhage After Lumboperitoneal Shunt for Fulminant Idiopathic Intracranial Hypertension.

A 33-year-old woman presented with severe visual loss from fulminant idiopathic intracranial hypertension. Her lumbar puncture opening pressure was 97 cm H2O. Soon after lumboperitoneal shunt surgery, she had a generalized tonic-clonic seizure. Magnetic resonance imaging demonstrated frontal subarachnoid hemorrhage (SAH) and neuroimaging findings consistent with posterior reversible encephalopathy syndrome (PRES). We hypothesize that an abrupt drop in intracranial pressure after lumboperitoneal shunting led to maladjustment of cerebral vascular autoregulation, which caused SAH and PRES.

The significance of α-synuclein, amyloid-ß and tau pathologies in Parkinson's disease progression and related dementia.

BACKGROUND: Dementia is one of the milestones of advanced Parkinson's disease (PD), with its neuropathological substrate still being a matter of debate, particularly regarding its potential mechanistic implications. OBJECTIVE: The aim of this study was to review the relative importance of Lewy-related α-synuclein and Alzheimer's tau and amyloid-ß (Aß) pathologies in disease progression and dementia in PD. METHODS: We reviewed studies conducted at the Queen Square Brain Bank, Institute of Neurology, University College London, using large PD cohorts. RESULTS: Cortical Lewy- and Alzheimer-type pathologies are associated with milestones of poorer prognosis and with non-tremor predominance, which have been, in turn, linked to dementia. The combination of these pathologies is the most robust neuropathological substrate of PD-related dementia, with cortical Aß burden determining a faster progression to dementia. CONCLUSION: The shared relevance of these pathologies in PD progression and dementia is in line with experimental data suggesting synergism between α-synuclein, tau and Aß and with studies testing these proteins as disease biomarkers, hence favouring the eventual testing of therapeutic strategies targeting these proteins in PD.

Wearable Accelerometer and Gyroscope Sensors for Estimating the Severity of Essential Tremor.

BACKGROUND: Several validated clinical scales measure the severity of essential tremor (ET). Their assessments are subjective and can depend on familiarity and training with scoring systems. METHOD: We propose a multi-modal sensing using a wearable inertial measurement unit for estimating scores on the Fahn-Tolosa-Marin tremor rating scale (FTM) and determine the classification accuracy within the tremor type. 17 ET participants and 18 healthy controls were recruited for the study. Two movement disorder neurologists who were blinded to prior clinical information viewed video recordings and scored the FTM. Participants drew a guided Archimedes spiral while wearing an inertial measurement unit placed at the mid-point between the lateral epicondyle of the humerus and the anatomical snuff box. Acceleration and gyroscope recordings were analyzed. The ratio of the power spectral density between frequency bands 0.5-4 Hz and 4-12 Hz, and the sum of power spectrum density over the entire spectrum of 2-74 Hz, for both accelerometer and gyroscope data, were computed. FTM was estimated using regression model and classification using SVM was validated using the leave-one-out method. RESULTS: Regression analysis showed a moderate to good correlation when individual features were used, while correlation was high ([Formula: see text] = 0.818) when suitable features of the gyro and accelerometer were combined. The accuracy for two-class classification of the combined features using SVM was 91.42% while for four-class it was 68.57%. CONCLUSION: Potential applications of this novel wearable sensing method using a wearable Inertial Measurement Unit (IMU) include monitoring of ET and clinical trials of new treatments for the disorder.

Neuropathological findings in benign tremulous parkinsonism.

Benign tremulous parkinsonism, a tremor dominant syndrome with a relatively slow rate of deterioration, is recognized by clinicians although its pathological basis is not well understood. A systematic review of Queen Square Brain Bank donors was carried out to determine the natural history and pathology of individuals who had tremor dominant parkinsonism with mild non-tremor components and minimal gait disability for at least 8 years. We identified 16 cases of pathologically proved benign tremulous Parkinson's disease (PD); another 5 individuals conformed to the definition but did not have the pathology of PD. Patients with verified benign tremulous PD had less severe neuronal loss in the substantia nigra than controls (χ(2): P = .003). Twelve of these had been correctly diagnosed with PD at their first neurological evaluation, whereas the other 4 were originally thought to have another tremor disorder. The only consistent distinguishing feature of the 5 pathologically disproved cases, who may have had either essential tremor with associated rest tremor or dystonic tremor, was a failure to develop unequivocal bradykinesia within a decade of onset of tremor at rest. Our findings support the existence of a distinct subgroup of benign tremulous PD. The slower rate of clinical progression correlates with less severe nigral cell loss at postmortem, although many of these patients transgress the benign tremulous parkinsonism definition by the final third of their disease course and develop the common features of advanced PD.

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 Parkinson's 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 Parkinson's disease has an exponential pattern of progression.

Neurology and detective writing.

When searching for clues to reach a diagnosis, neurologists often empathise with the detective who is trying to solve a case. The premise of this article is that detective stories have been part of the fabric of neurology ever since the time that it evolved into a discrete medical speciality. We will examine how this form of narrative has found expression in detective mystery fiction and popular science publications created by 20th century neurologist physician-writers. We will also investigate the power of the neurologist's alter ego, Sherlock Holmes: his relationship to founders of clinical neuroscience such as Jean-Martin Charcot, William Gowers and Sigmund Freud, and his influences on neurological practice and its literary traditions.

Movement disorders in cell surface antibody mediated autoimmune encephalitis: a meta-analysis.

Background: Autoimmune encephalitis (AE) is an increasingly recognized neuroinflammatory disease entity in which early detection and treatment leads to the best clinical outcomes. Movement disorders occur in AE but their characteristics are not well defined. Objectives: To identify the frequency, classification, and prognostic significance of movement disorders in AE. Methods: We conducted a systematic review and random-effects meta-analysis of movement disorders in cell surface antibody mediated AE. The frequency of any movement disorder as well as the classification of movement disorders in AE serotypes was determined. We looked at adults 18 years and older and included publications that described at least 10 cases. We used the following four electronic databases: Medline (Ovid), EMBASE (Ovid), APA Psychinfo, and Cochrane library. Results: A total of 1,192 titles and abstracts were reviewed. Thirty-seven studies were included in the final meta-analysis. At least one kind of movement disorder was present in 40% of the entire AE cohort, 53% with anti-NMDA receptor antibodies, 33% with anti-CASPR2 antibodies, 30% with anti-LGI1 antibodies and 13% with anti-GABA receptor antibodies. Dyskinesia was the commonest movement disorder in anti-NMDA antibody mediated AE and faciobrachial dystonic seizures were most frequent in anti-LGI1 antibody mediated AE. Patients with a movement disorder tended to have a higher mortality. The risk of bias in the included studies was mostly moderate or high. Conclusion: Movement disorders are common in AE and their identification, in conjunction with other clinical and paraclinical features, may facilitate earlier diagnosis. The prognostic implications of movement disorders in AE warrant further dedicated study. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42023386920.

Protocol for a home-based integrated physical therapy program to reduce falls and improve mobility in people with Parkinson's disease.

BACKGROUND: The high incidence of falls associated with Parkinson's disease (PD) increases the risk of injuries and immobility and compromises quality of life. Although falls education and strengthening programs have shown some benefit in healthy older people, the ability of physical therapy interventions in home settings to reduce falls and improve mobility in people with Parkinson's has not been convincingly demonstrated. METHODS/DESIGN: 180 community living people with PD will be randomly allocated to receive either a home-based integrated rehabilitation program (progressive resistance strength training, movement strategy training and falls education) or a home-based life skills program (control intervention). Both programs comprise one hour of treatment and one hour of structured homework per week over six weeks of home therapy. Blinded assessments occurring before therapy commences, the week after completion of therapy and 12 months following intervention will establish both the immediate and long-term benefits of home-based rehabilitation. The number of falls, number of repeat falls, falls rate and time to first fall will be the primary measures used to quantify outcome. The economic costs associated with injurious falls, and the costs of running the integrated rehabilitation program from a health system perspective will be established. The effects of intervention on motor and global disability and on quality of life will also be examined. DISCUSSION: This study will provide new evidence on the outcomes and cost effectiveness of home-based movement rehabilitation programs for people living with PD. TRIAL REGISTRATION: The trial is registered on the Australian and New Zealand Clinical Trials Registry (ACTRN12608000390381).

Parkinson's disease, dopaminergic drugs and the plant world.

A large proportion of drugs used for the treatment of neurological disorders relate to naturally occurring compounds, many of which are plant alkaloids. This is particularly true of Parkinson's disease (PD). The pharmacopoeia of PD has strong botanical origins, while major discoveries about the neurochemistry of the basal ganglia came from the study of phytochemicals. This article narrates the development of pharmacotherapy for PD in terms of historically important plant-derived substances-tropane and hamala alkaloids, reserpine, levodopa, apomorphine, and ergoline dopamine receptor agonists. Alkaloids are nitrogen-containing secondary metabolic products that tend to be biologically active. They appear to be involved in plants' adaptation to herbivorous animals, though their exact purpose and the ways in which they work are uncertain. A sizable group of alkaloids influence animal dopaminergic systems, highlighting a key biological relationship. While animals must acquire the energy that plants harness, plants need to engage with the animal attribute that they lack-movement-in order to maximize their reproductive fitness. Neuroactive flowering plant compounds have been interacting with vertebrate and invertebrate motor systems for 100 million years. A deep evolutionary connection helps to explain why the pharmacological treatment of PD is imprinted with the power of these mysterious botanical chemicals.

Computerized analysis of speech and voice for Parkinson's disease: A systematic review.

BACKGROUND AND OBJECTIVE: Speech impairment is an early symptom of Parkinson's disease (PD). This study has summarized the literature related to speech and voice in detecting PD and assessing its severity. METHODS: A systematic review of the literature from 2010 to 2021 to investigate analysis methods and signal features. The keywords "Automatic analysis" in conjunction with "PD speech" or "PD voice" were used, and the PubMed and ScienceDirect databases were searched. A total of 838 papers were found on the first run, of which 189 were selected. One hundred and forty-seven were found to be suitable for the review. The different datasets, recording protocols, signal analysis methods and features that were reported are listed. Values of the features that separate PD patients from healthy controls were tabulated. Finally, the barriers that limit the wide use of computerized speech analysis are discussed. RESULTS: Speech and voice may be valuable markers for PD. However, large differences between the datasets make it difficult to compare different studies. In addition, speech analytic methods that are not informed by physiological understanding may alienate clinicians. CONCLUSIONS: The potential usefulness of speech and voice for the detection and assessment of PD is confirmed by evidence from the classification and correlation results.

Geste Antagoniste Effects on Motor Performance in Dystonia-A Kinematic Study.

Background: The kinematic effects of gestes have not previously been studied. The mechanism(s) by which these sensory tricks modify dystonic movement is not well understood. Objectives: A kinematic investigation of the geste phenomenon in patients with dystonia. Methods: Twenty-three patients with dystonia associated with a geste were studied. Twenty-nine healthy controls also participated. Fifteen seconds of finger tapping was recorded by electromagnetic sensors, and the task was repeated with geste. Separable motor components were extracted using a custom-written MATLAB script. Performance with and without geste was compared using Wilcoxon signed ranks testing. Results: Speed and fluency of finger tapping is impaired in dystonia. When patients executed their geste, speed of movement (amplitude × frequency) increased (P < 0.0001), and halts decreased (P = 0.007). Conclusions: That gestes improve not only dystonic muscle contraction but also the efficiency of voluntary movement suggests a broad influence at the premotor control stage.

Wearable sensors during drawing tasks to measure the severity of essential tremor.

Commonly used methods to assess the severity of essential tremor (ET) are based on clinical observation and lack objectivity. This study proposes the use of wearable accelerometer sensors for the quantitative assessment of ET. Acceleration data was recorded by inertial measurement unit (IMU) sensors during sketching of Archimedes spirals in 17 ET participants and 18 healthy controls. IMUs were placed at three points (dorsum of hand, posterior forearm, posterior upper arm) of each participant's dominant arm. Movement disorder neurologists who were blinded to clinical information scored ET patients on the Fahn-Tolosa-Marin rating scale (FTM) and conducted phenotyping according to the recent Consensus Statement on the Classification of Tremors. The ratio of power spectral density of acceleration data in 4-12 Hz to 0.5-4 Hz bands and the total duration of the action were inputs to a support vector machine that was trained to classify the ET subtype. Regression analysis was performed to determine the relationship of acceleration and temporal data with the FTM scores. The results show that the sensor located on the forearm had the best classification and regression results, with accuracy of 85.71% for binary classification of ET versus control. There was a moderate to good correlation (r2 = 0.561) between FTM and a combination of power spectral density ratio and task time. However, the system could not accurately differentiate ET phenotypes according to the Consensus classification scheme. Potential applications of machine-based assessment of ET using wearable sensors include clinical trials and remote monitoring of patients.

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

BACKGROUND: This randomized double blind, placebo-controlled crossover study investigated the antidyskinetic effects of levetiracetam in Parkinson's disease. METHODS: Sixteen participants with levodopa-induced dyskinesia were enrolled. Hourly videotaped dyskinesia assessments scored by the Goetz method and hourly Unified Parkinson's Disease Rating Scale motor subscale scoring were conducted on 1 day at the end of each treatment period. RESULTS: Dyskinesia was slightly less on placebo (P = .26). Patient diary records also showed less dyskinesia on placebo (P = .10). Parkinsonism was a little worse on levetiracetam, at borderline statistical significance (P = .05). CONCLUSIONS: Levetiracetam was well tolerated at doses up to 2000 mg per day, but we did not detect any antidyskinetic properties.