Additional Neurological Signs Research Articles

Neurocysticercosis and cognitive impairment among people with epilepsy in Taenia solium endemic regions of rural southern Tanzania: A hospital-based cross-sectional study in mental health clinics of selected sites in Tanzania

BackgroundEpilepsy poses a significant public health problem in many parts of the world. The majority of people with epilepsy (PWE) are from low-income and middle-income countries (LMICs). Taenia solium neurocysticercosis (NCC) is estimated to cause 30% of preventable epilepsy in PWE in areas of T. solium endemicity. This study was conducted to assess the prevalence of NCC in PWE, evaluate the presence of cognitive impairment in PWE, and assess potential contributing factors. MethodsPWE were recruited within a mental health clinic-based cross-sectional study in rural Southern Tanzania. PWE underwent a detailed neurological examination, and a blood sample was collected for T. solium cysticercosis (CC) serology testing. Patients who were serologically positive for CC and those detected to have prominent neurological deficits apart from epilepsy were invited to receive a cerebral computed tomography (CT) examination. ResultsOut of the 223 people with epilepsy (PWE) recruited, 221 underwent clinical examination. Among these, 26 (11.8 %) had cognitive impairment, and 2 had additional neurological signs or symptoms. Twenty-five of the 223 PWE (11.2 %) tested positive for CC. A total of 36 participants underwent CT scans, with 18 testing positives for CC and 18 negatives. Of the 36 who had CT scans, 8 (22.2 %) were diagnosed with NCC; 7 were CC positive, and 1 was CC negative. Multivariate logistic regression confirmed that cognitive impairment in PWE was 8.62 times higher for Kongwa participants compared to Chunya, with a statistically significant association (95 % CI: 1.75–156; P<0.037). Additionally, having an education was associated with a 91 % reduction in the odds of NCC (OR=0.09) compared to no education, which was also statistically significant (95 % CI: 0.01 to 0.33; P<0.002). ConclusionOur study found a 22.2% prevalence of neurocysticercosis (NCC) among PWE. Cognitive impairment was present in 11.8% of PWE but was not significantly associated with NCC. Socioeconomic and educational factors may play a larger role in cognitive impairment among PWE.

Deoxyguanosine kinase deficiency: natural history and liver transplant outcome.

Autosomal recessive pathogenetic variants in the DGUOK gene cause deficiency of deoxyguanosine kinase activity and mitochondrial deoxynucleotides pool imbalance, consequently, leading to quantitative and/or qualitative impairment of mitochondrial DNA synthesis. Typically, patients present early-onset liver failure with or without neurological involvement and a clinical course rapidly progressing to death. This is an international multicentre study aiming to provide a retrospective natural history of deoxyguanosine kinase deficient patients. A systematic literature review from January 2001 to June 2023 was conducted. Physicians of research centres or clinicians all around the world caring for previously reported patients were contacted to provide followup information or additional clinical, biochemical, histological/histochemical, and molecular genetics data for unreported cases with a confirmed molecular diagnosis of deoxyguanosine kinase deficiency. A cohort of 202 genetically confirmed patients, 36 unreported, and 166 from a systematic literature review, were analyzed. Patients had a neonatal onset (≤ 1 month) in 55.7% of cases, infantile (>1 month and ≤ 1 year) in 32.3%, pediatric (>1 year and ≤18 years) in 2.5% and adult (>18 years) in 9.5%. Kaplan-Meier analysis showed statistically different survival rates (P < 0.0001) among the four age groups with the highest mortality for neonatal onset. Based on the clinical phenotype, we defined four different clinical subtypes: hepatocerebral (58.8%), isolated hepatopathy (21.9%), hepatomyoencephalopathy (9.6%), and isolated myopathy (9.6%). Muscle involvement was predominant in adult-onset cases whereas liver dysfunction causes morbidity and mortality in early-onset patients with a median survival of less than 1 year. No genotype-phenotype correlation was identified. Liver transplant significantly modified the survival rate in 26 treated patients when compared with untreated. Only six patients had additional mild neurological signs after liver transplant. In conclusion, deoxyguanosine kinase deficiency is a disease spectrum with a prevalent liver and brain tissue specificity in neonatal and infantile-onset patients and muscle tissue specificity in adult-onset cases. Our study provides clinical, molecular genetics and biochemical data for early diagnosis, clinical trial planning and immediate intervention with liver transplant and/or nucleoside supplementation.

Neurological disease in xeroderma pigmentosum: prospective cohort study of its features and progression.

Xeroderma pigmentosum (XP) results from biallelic mutations in any of eight genes involved in DNA repair systems, thus defining eight different genotypes (XPA, XPB, XPC, XPD, XPE, XPF, XPG and XP variant or XPV). In addition to cutaneous and ophthalmological features, some patients present with XP neurological disease. It is unknown whether the different neurological signs and their progression differ among groups. Therefore, we aim to characterize the XP neurological disease and its evolution in the heterogeneous UK XP cohort. Patients with XP were followed in the UK National XP Service, from 2009 to 2021. Age of onset for different events was recorded. Cerebellar ataxia and additional neurological signs and symptoms were rated with the Scale for the Assessment and Rating of Ataxia (SARA), the Inventory of Non-Ataxia Signs (INAS) and the Activities of Daily Living questionnaire (ADL). Patients' mutations received scores based on their predicted effects. Data from available ancillary tests were collected. Ninety-three XP patients were recruited. Thirty-six (38.7%) reported neurological symptoms, especially in the XPA, XPD and XPG groups, with early-onset and late-onset forms, and typically appearing after cutaneous and ophthalmological symptoms. XPA, XPD and XPG patients showed higher SARA scores compared to XPC, XPE and XPV. SARA total scores significantly increased over time in XPD (0.91 points/year, 95% confidence interval: 0.61, 1.21) and XPA (0.63 points/year, 95% confidence interval: 0.38, 0.89). Hyporeflexia, hypopallesthaesia, upper motor neuron signs, chorea, dystonia, oculomotor signs and cognitive impairment were frequent findings in XPA, XPD and XPG. Cerebellar and global brain atrophy, axonal sensory and sensorimotor neuropathies, and sensorineural hearing loss were common findings in patients. Some XPC, XPE and XPV cases presented with abnormalities on examination and/or ancillary tests, suggesting underlying neurological involvement. More severe mutations were associated with a faster progression in SARA total score in XPA (0.40 points/year per 1-unit increase in severity score) and XPD (0.60 points/year per 1-unit increase), and in ADL total score in XPA (0.35 points/year per 1-unit increase). Symptomatic and asymptomatic forms of neurological disease are frequent in XP patients, and neurological symptoms can be an important cause of disability. Typically, the neurological disease will be preceded by cutaneous and ophthalmological features, and these should be actively searched in patients with idiopathic late-onset neurological syndromes. Scales assessing cerebellar function, especially walking and speech, and disability can show progression in some of the groups. Mutation severity can be used as a prognostic biomarker for stratification purposes in clinical trials.

Idiopathic and structural episodic nonintentional head tremor in dogs: 100 cases (2004-2022).

Although idiopathic episodic head tremor (IEHT) in dogs is well-known, little is known about structural brain lesions causing structural episodic head tremor (SEHT). Describe semiology, magnetic resonance imaging (MRI) findings and outcome of dogs with IEHT or SEHT. We hypothesized that structural lesions affecting the middle cranial fossa or mesencephalic aqueduct could lead to SEHT. One hundred dogs with IEHT (n = 71) or SEHT (n = 29). Retrospective, multicenter, study of dogs with episodic (nonintentional) head tremor and brain MRI between 2004 and 2022. Lesions on MRI in SEHT dogs were localized to the middle cranial fossa (15/29), cerebrocortex (3/29), brainstem (2/29), fourth ventricle (1/29) or multifocal (8/29) with thalamus involvement (6/8). Secondary compression of the mesencephalic aqueduct (19/29), third ventricle or interthalamic adhesion or both (14/29) was common. The most common underlying condition in dogs with SEHT was a pituitary mass. Dogs with SEHT were older, had additional neurological signs and were more likely to be euthanized after diagnosis (P < .001 for all) compared to IEHT dogs. Two SEHT dogs had only tremor. In IEHT dogs, 8/10 owners reported that the tremor decreased or abated over time (range, 106-2315 days) without treatment. Tremor remission occurred in SEHT dogs treated for underlying meningoencephalitis. Presence of additional neurological signs and older age may indicate an underlying structural cause for episodic (nonintentional) head tremor involving the mesencephalic aqueduct, third ventricle, interthalamic adhesion or some combination of these. An intracranial structural abnormality cannot be excluded in dogs with normal neurological examination.

Dizziness Evaluation and Characterisation of Patients with Posterior Circulation Stroke in the Emergency Department; a Case Series Study.

Dizziness is a common scenario in the Emergency Departments (EDs). Among dizziness underlying causes, the posterior circulation stroke is especially relevant due to its mobimortality and concerning misdiagnosis rates. Therefore, we conducted this study to assess dizziness evaluation and baseline characteristics of patients with PS in the ED. We conducted a 3-year retrospective observational study on PS cases confirmed by magnetic resonance imaging (MRI). Concretely, we analysed the demographic profile of these patients, the initial PS clinical presentation, and diagnostic workup (with emphasis on dizziness evaluation) performed at the ED. During the study period, 85 cases were registered. Risk factors for cardiovascular disease were present in 85.5% and previous visits to the ED due to dizziness were recorded in 16.5%. The main clinical presentation was dizziness, concretely as an acute vestibular syndrome (38.8%) with additional neurological signs or symptoms (80%). Evaluation by the otolaryngologist on call was requested in less than 10% of the cases and included the HINTS protocol use with a sensitivity of 100% for central nervous system underlying causality. A brain CT study was always performed with a sensitivity of 27%. However, 96.47% of patients were primarily admitted to the Neurology hospitalization ward and MRI was always performed in a mean time of 3.21 days confirming the diagnosis. Dizziness is the most frequent symptom of PS. Patients usually present an AVS (associated with additional N-SS or not) and HINTS bedside examination is the most adequate protocol to differentiate a PS from other AVS causes until the diagnostic confirmation via MRI. Interestingly, mainly otolaryngologists seem to use HINTS. However, the use of CT is widespread despite its poor value.

Tremor, Gait, and Balance Disorders in Essential Tremor and the Efficacy of Atenolol

ABSTRACT Background: To assess gait and balance in patients with essential tremor (ET), which is the most common tremor disorder characterized by bilateral action tremor of the hands with possible involvement of further tremor locations and to test the efficacy of atenolol on tremor and gait and balance. Methods: In this prospective study, gait and balance were evaluated by static posturography in addition to International Cooperative Ataxia Rating Scale (ICARS) in 22 ET patients without any additional neurologic signs on examination. Tremor severity was assessed by The Essential Tremor Rating Assessment Scale (TETRAS). The efficacy of atenolol 100 mg/day both on tremor and gait and balance was investigated. Posturographic recordings were performed in gender, age-, and height-matched healthy volunteers who constituted the control group. Results: The mean center of gravity sway velocity of the ET patients recorded on firm and foam surfaces with eyes open and closed was not significantly different from the healthy controls but sway velocity on tandem stance was significantly increased (P = 0.032). Gait speed (P = 0.015) was decreased and step width was increased (P = 0.001). An improvement in TETRAS scores was recorded with atenolol treatment (P = 0.046). An improvement not reaching statistical significance was present in ICARS scores (P = 0.059). However, posturographic parameters did not change significantly (P &gt; 0.05). Conclusion: Increased sway velocity on tandem stance, decreased gait speed and increased step width are consistent with midline cerebellar dysfunction in ET patients with no obvious gait and balance deficits on clinical examination. Atenolol seems to be effective on tremor but does not cause a significant improvement in gait and balance deficits.

Vascular vertigo and dizziness: Diagnostic criteria.

This paper presents diagnostic criteria for vascular vertigo and dizziness as formulated by the Committee for the Classification of Vestibular Disorders of the Bárány Society. The classification includes vertigo/dizziness due to stroke or transient ischemic attack as well as isolated labyrinthine infarction/hemorrhage, and vertebral artery compression syndrome. Vertigo and dizziness are among the most common symptoms of posterior circulation strokes. Vascular vertigo/dizziness may be acute and prolonged (≥24 hours) or transient (minutes to < 24 hours). Vascular vertigo/dizziness should be considered in patients who present with acute vestibular symptoms and additional central neurological symptoms and signs, including central HINTS signs (normal head-impulse test, direction-changing gaze-evoked nystagmus, or pronounced skew deviation), particularly in the presence of vascular risk factors. Isolated labyrinthine infarction does not have a confirmatory test, but should be considered in individuals at increased risk of stroke and can be presumed in cases of acute unilateral vestibular loss if accompanied or followed within 30 days by an ischemic stroke in the anterior inferior cerebellar artery territory. For diagnosis of vertebral artery compression syndrome, typical symptoms and signs in combination with imaging or sonographic documentation of vascular compromise are required.

Parkinson Disease

Parkinson Disease Jaime Moore (bio) and Jessica Kandl (bio) CARE OF THE PROFESSIONAL VOICE Parkinson disease (PD) is a progressive neurological disorder that affects approximately two million Americans.1 Typically, this disease presents in either sex after the age of 60; however, it can present in individuals as young as 30. It is the second most common neurodegenerative disorder facing the elderly.2 In addition to affecting movement, 70–90% of patients also experience Parkinson-related voice and speech disturbance, and up to 1/3 of these patients identify the voice and speech symptoms as the most debilitating deficits related to the disease.3 Parkinson disease can be challenging in singers and it is imperative that singing teachers and professional voice users recognize the effects of PD on the voice and speech and be familiar with treatment options. WHAT IS PARKINSON DISEASE? Parkinson disease is a neurologic disease caused by death of neurons in the substantia nigra, a dopamine-producing region of the brain.4 Subsequently, there is a decrease in production of dopamine, an important neurotransmitter. The substantia nigra is part of the basal ganglia, a region of the brain crucial in movement; therefore, changes in the neurotransmitters in this region lead to motor impairment, including difficulty walking resting, speech and voice impairment, tremor, rigidity (stiffness), and bradykinesia (slow movements). In addition to motor symptoms, the disease can cause depression, sleep disturbance, voice changes, and possibly cognitive impairments. Voice changes can be the first sign of PD, and recognizing these changes is important in ensuring that the patient receives the necessary care.5 Parkinson disease should be distinguished from the Parkinson Plus Syndromes such as multisystem atrophy.6 This group of syndromes is defined by Parkinson symptoms, but with additional clinic features such as rapid progression, early dementia, vision changes, and frequent falls. Vocal and speech disturbances in PD include hypokinetic dysarthrias marked by monopitch and slowed speech, reduced stress, imprecise consonants, breathiness, and reduced loudness.7 Patients with PD also have abnormal vocal processing and auditory feedback, which leads to the patient perceiving the voice as normal when it is not.8 Singers might note loss of range, decreased loudness, prolonged warm-up, and increased vocal instability. These speech and voice changes can limit patients’ ability to convey emotions as well as decrease speech intelligibility.9 Decreased intelligibility can lead patients with Parkinson disease to limit social interaction, which may result in isolation and decreased quality of life. [End Page 609] EVALUATION Patients diagnosed with Parkinson dysphonia and/or dysarthria require a multidisciplinary team approach including evaluations by a neurologist, otolaryngologist, speech language pathologist, and other professionals. A complete head and neck exam should be conducted, and additional neurologic signs such as resting tremor, “pill rolling” finger movements, and decreased facial expression should be noted.10 As part of the evaluation, the larynx is visualized typically using videostrobolaryngoscopy. Vocal fold bowing and atrophy are seen commonly, and the vocal fold bowing is associated with glottal incompetence and compensatory muscle tension dysphonia.11 Vocal tremor and vocal paresis and paralysis also have been reported in these patients. Objective voice testing can demonstrate increased shimmer and jitter and decreased harmonic-to-noise ratio. In addition to voice complaints, patients often have difficulty swallowing and reduced sense of smell, and these symptoms may require additional evaluation.12 TREATMENT Typically, medical therapy to increase dopamine is the initial treatment for PD.13 This is done through a combination of medications that prevent degradation of dopamine and increase the supply of dopamine. The regimen requires adjustment as the disease progresses. These medications have been shown to improve motor symptoms of the disease like rigidity, bradykinesia, and resting tremor; however, there are mixed data about the vocal impact.14 Deep brain stimulation (DBS) is another treatment option that involves implanting electrodes into specific areas of the brain. These electrodes send electrical impulses that help regulate pathway activity in a more normal pattern. This treatment has been shown to dramatically improve overall motor function of the patient; however, the vocal results are variable, with some studies demonstrate a negative impact on vocal quality.15 As neither option specifically addresses Parkinson dysphonia, additional treatment typically...

Reclassification of patients with tremor syndrome and comparisons of essential tremor and essential tremor-plus patients.

The new essential tremor (ET)-plus nomenclature was proposed by the 2018 Tremor Consensus Criteria. However, few studies have adopted this usage and the clinical differences between ET and ET-plus remains unclear. To address this issue, we reclassified and compared the characteristics of ET and ET-plus patients in a large Chinese tremor cohort. In this cross-sectional observational study, 766 patients originally diagnosed with ET underwent neurological examination. Scale ratings were used to evaluate motor and non-motor symptoms, and quality of life (QoL). We then reclassified the ET cohort and compared demographic and clinical characteristics between ET and ET-plus patients. A logistic regression analysis was used to explore whether the presence of neurological soft signs in ET-plus was associated with tremor severity or QoL. Among 665 clinically confirmed ET syndrome patients, 274 were ET and 391 were ET-plus. The most prevalent neurological soft sign was resting tremor. ET-plus patients were older, had older age at onset and longer disease duration. ET-plus patients recorded higher scores in tremor severity evaluations and lower in cognitive evaluations, whereas a higher proportion of patients presented with depression or anxiety symptoms. Resting tremor and questionable cerebellar signs were associated with tremor severity. Cognitive impairment was associated with worse QoL. ET-plus patients were older, had longer disease durations, worse tremor manifestations, and more distinct non-motor symptoms. Certain additional soft signs of ET-plus were associated with tremor severity or worse QoL. ET-plus patients may include advanced ET patients with additional neurological soft signs presenting along with disease progression.

Bayesian Interpretation of Essential Tremor Plus.

Essential tremor (ET) plus is a new tremor classification that was introduced in 2018 by a task force of the International Parkinson and Movement Disorder Society. Patients with ET plus meet the criteria for ET but have one or more additional systemic or neurologic signs of uncertain significance or relevance to tremor (“soft signs”). Soft signs are not sufficient to diagnose another tremor syndrome or movement disorder, and soft signs in ET plus are known to have poor interrater reliability and low diagnostic sensitivity and specificity. Therefore, the clinical significance of ET plus must be interpreted probabilistically when judging whether a patient is more likely to have ET or a combined tremor syndrome, such as dystonic tremor. Such a probabilistic interpretation is possible with Bayesian analysis. This review presents a Bayesian analysis of ET plus in patients suspected of having ET versus a dystonic tremor syndrome, which is the most common differential diagnosis in patients referred for ET. Bayesian analysis of soft signs provides an estimate of the probability that a patient with possible ET is more likely to have an alternative diagnosis. ET plus is a distinct tremor classification and should not be viewed as a subtype of ET. ET plus covers a more-comprehensive phenotyping of people with possible ET, and the clinical interpretation of ET plus is enhanced with Bayesian analysis of associated soft signs.

Response to Thalamic Ventralis Intermedius Nucleus Deep Brain Stimulation in Essential Tremor vs. Essential Tremor-Plus.

Introduction: Essential tremor (ET) is a tremor syndrome characterized by bilateral, upper limb action tremor. Essential tremor-plus (ET-plus) describes ET patients with additional neurologic signs. It is unknown whether there is a difference in response to treatment with ventralis intermedius nucleus deep brain stimulation (VIM DBS) in patients with ET and ET-plus. Due to potential variability in underlying etiology in ET-plus, there is a concern that ET-plus patients may have worse outcomes. The aim of this study was to identify whether patients with ET-plus have worse tremor outcomes after VIM DBS than patients with ET.Methods: This is a retrospective chart and video review evaluating VIM DBS outcomes by comparing changes from baseline in the Fahn-Tolosa-Marin Tremor Rating Scale Part B (FTM-B) for the treated limb between patients with ET and ET-plus at follow-up examinations. Patients were re-classified as having ET or ET-plus using pre-operative examination videos by two independent movement disorders neurologists blinded to patient characteristics. As a secondary outcome, we evaluated for correlations and potential predictors of treatment response.Results: Twenty-six patients were included: 13 with ET, 13 with ET-plus. There were no significant differences in the change in FTM-B scores between the ET and ET-plus patients at each follow-up examination. None of the included patients developed new symptoms compatible with dystonia, parkinsonism or gait disturbances.Conclusions: Patients with ET-plus had tremor improvement from VIM DBS, with no differences when compared to those with ET, without emergence of postoperative neurological issues. Patients with ET-plus should still be considered good candidates for VIM DBS for treatment of tremor.

Essential Tremors: A Detailed Review

Essential tremor (ET) is the most prevalent movement disorder globally and is ten times more prevalent than Parkinson's. It is considered one of the most common movement disorders with various treatment options reported in clinical practice but uncertainty about the most robust one. The International Parkinson and Movement Disorder Society recently reviewed the clinical studies of essential tremors and updated the treatment guidelines. Mild to moderate tremor severity can sometimes be managed with occupational treatment such as speech therapy or adaptation. In contrast, the first-line pharmacological treatments include symptomatic treatment with propranolol, primidone, and topiramate. Botulinum toxin is preferred for selected cases, whereas invasive treatments should be considered a severe essential tremor treatment option. Focused ultrasound thalamotomy is attracting a lot of attention as a new therapy for essential tremors. Misdiagnosis among tremor syndromes is another point of concern and impacts both clinical care and research. A new neurophysiological measure, known as the tremor stability index, is introduced recently to attain diagnostic accuracy between Parkinson's disease tremor and essential tremor. Also, ET-Plus is a newly suggested term for the classification of tremor in the recent Consensus statement, which acknowledges the presence of additional neurological signs in patients with ET. This review includes in detail defining ET, hypothesis about ET, clinical features along with points to consider while differentiating between ET and Parkinson's Disease (PD), evaluation of ET based on laboratory findings, treatment procedures, measures to reduce misdiagnosis between ET and PD, and reality about the new term ET-Plus syndrome.

X-Linked Parkinsonism: Phenotypic and Genetic Heterogeneity.

X-linked parkinsonism encompasses rare heterogeneous disorders mainly inherited as a recessive trait, therefore being more prevalent in males. Recent developments have revealed a complex underlying panorama, including a spectrum of disorders in which parkinsonism is variably associated with additional neurological and non-neurological signs. In particular, a childhood-onset encephalopathy with epilepsy and/or cognitive disability is the most common feature. Their genetic basis is also heterogeneous, with many causative genes and different mutation types ranging from "classical" coding variants to intronic repeat expansions. In this review, we provide an updated overview of the phenotypic and genetic spectrum of the most relevant X-linked parkinsonian syndromes, namely X-linked dystonia-parkinsonism (XDP, Lubag disease), fragile X-associated tremor/ataxia syndrome (FXTAS), beta-propeller protein-associated neurodegeneration (BPAN, NBIA/PARK-WDR45), Fabry disease, Waisman syndrome, methyl CpG-binding protein 2 (MeCP2) spectrum disorder, phosphoglycerate kinase-1 deficiency syndrome (PGK1) and X-linked parkinsonism and spasticity (XPDS). All clinical and radiological features reported in the literature have been reviewed. Epilepsy occasionally represents the symptom of onset, predating parkinsonism even by a few years; action tremor is another common feature along with akinetic-rigid parkinsonism. A focus on the genetic background and its pathophysiological implications is provided. The pathogenesis of these disorders ranges from well-defined metabolic alterations (PGK1) to non-specific lysosomal dysfunctions (XPDS) and vesicular trafficking alterations (Waisman syndrome). However, in other cases it still remains poorly defined. Recognition of the phenotypic and genetic heterogeneity of X-linked parkinsonism has important implications for diagnosis, management, and genetic counseling. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Exploring Interrater Disagreement on Essential Tremor Using a Standardized Tremor Elements Assessment.

BackgroundPatients with upper limb action tremor frequently exhibit additional neurological signs of uncertain significance. Clinicians vary in their interpretation, and interrater agreement on the final diagnosis is poor.ObjectivesA new clinical tool for assessing the presence or absence of clinical signs that are important in axis‐1 classification of tremor patients is introduced: the Standardized Tremor Elements Assessment (STEA). Interrater agreement is determined, and signs leading to disagreement in the final diagnosis are identified.MethodsThree tremor‐focussed and one dystonia‐focussed movement disorder specialists rated 59 videos of patients with upper limb action tremor syndromes using STEA. Interrater agreements for final diagnosis and STEA items were calculated.ResultsInterrater agreement regarding the final diagnosis was higher within the group of tremor specialists and poor between dystonia and tremor specialists. Greater agreement was found for items characterizing tremor than for signs of dystonia.ConclusionsClinical signs leading to diagnostic disagreement were identified with STEA, and STEA should therefore be useful in future studies of diagnostic disagreement. The thresholds for considering neurological signs as soft versus significant for ataxia, parkinsonism, dystonia, etc. are critically important in tremor classification and must be studied across movement disorder subspecialties, not simply within a pool of tremor specialists.

Thalamic Deep Brain Stimulation in Essential Tremor Plus Is as Effective as in Essential Tremor.

The new essential tremor (ET) classification defined ET-plus (ET-p) as an ET subgroup with additional neurological signs besides action tremor. While deep brain stimulation (DBS) is effective in ET, there are no studies specifically addressing DBS effects in ET-p. 44 patients with medication-refractory ET and thalamic/subthalamic DBS implanted at our center were postoperatively classified into ET and ET-p according to preoperative documentation. Tremor suppression with DBS (stimulation ON vs. preoperative baseline and vs. stimulation OFF), measured via the Fahn–Tolosa–Marin tremor rating scale (TRS), stimulation parameters, and the location of active contacts were compared between patients classified as ET and ET-p. TRS scores at baseline were higher in ET-p. ET-p patients showed comparable tremor reduction as patients with ET, albeit higher stimulation parameters were needed in ET-p. Active electrode contacts were located more dorsally in ET-p of uncertain reason. Our data show that DBS is similarly effective in ET-p compared to ET. TRS scores were higher in ET-p preoperatively, and higher stimulation parameters were needed for tremor reduction compared to ET. The latter may be related to a more dorsal location of active electrode contacts in the ET-p group of this cohort. Prospective studies are warranted to investigate DBS in ET-p further.

Beyond aphasia: Natural history of the aphasia onset dementia syndromes

AbstractBackgroundAphasic syndromes caused by neurodegenerative disease are known as Primary Progressive Aphasias (PPA). The most recent consensus criteria have classified PPA into the non‐fluent variant (nfPPA), semantic variant (svPPA) and the logopenic variant (lvPPA). Few longitudinal studies have explored the prognosis of patients with PPA. This study aims to give an overview of the clinical profile divided into different domains, the progression into other diagnoses and mortality of the different subtypes of PPA.MethodTwenty‐two patients diagnosed with nfPPA, 24 with svPPA and 18 with lvPPA between 2011 and 2019 were retrospectively collected and followed‐up for a maximum of over 6 years. Biomarkers and neuroimaging were acquired at baseline. Reported additional symptoms, neurological signs and outcomes on different neuropsychological tests during follow‐up period were collected and compared for baseline and longitudinal results. Kaplan‐ Meier survival analysis was performed for mortality rate.ResultAs expected, a language disorder was the main problem of all PPA patients at the first assessment. However, over the disease course, the subtypes exhibited a different progression pattern. Behavioural problems were prominent in svPPA whereas patients with lvPPA exhibited a greater executive and visuospatial dysfunction and episodic memory impairment (p&lt;0.05). Unlike svPPA and lvPPA, nfPPA subjects presented a relatively pure aphasia profile initially. However, 50% of the subjects developed extrapyramidal and pyramidal signs within 4 years and progressed into other diagnoses such as corticobasal degeneration, progressive supranuclear palsy, motor neuron disease, behavioural variant frontotemporal dementia and Alzheimer’s disease. Furthermore, in this group the mortality rate was significantly higher in comparison to the other subtypes (median years 3.04 [1.06 – 5.62], p=0.001). By contrast, none of the svPPA patients progressed into another diagnosis whereas 78% of the lvPPA patients progressed to Alzheimer’s disease within 3 years (Figure 1).ConclusionTo our knowledge, this is the first study to determine the progression profiles and the entire course of the disease from the diagnosis to the death. Our results show that prognosis differs widely per PPA subgroup. Disclosing the risk of developing motor symptoms should be considered in the case of nfPPA.

Essential tremor plus syndromes in clinical practice

On the 2018 consensus statement of the Movement Disorder Society on tremor introduced a new term “essential tremor plus” (ET-plus). This term means that the patient can have a clinical picture of ET and additional neurological signs such as dystonia or rigidity, or impaired tandem gait, or cognitive impairment, etc. These extra symptoms cast doubt on the reliability of the ET diagnosis, sometimes even exclude it. It is hard to clarify if it is ET-plus or for example dystonic tremor or ataxia with tremor.

The Problem of Questionable Dystonia in the Diagnosis of 'Essential Tremor-Plus'.

In a recent consensus statement on tremor, the task force of the International Parkinson and Movement Disorder Society proposed a new term, ‘essential tremor-plus (ET-plus)’ which includes patients with the characteristics of essential tremor (ET) and additional soft neurological signs of uncertain significance such as questionable dystonic posturing. The clinical interpretation of questionable dystonia has been left to the investigator. The consensus statement also stated that the ET-plus syndrome does not include other clearly defined syndromes like dystonic tremor. However, the boundary between questionable dystonia and definite dystonia is not distinct leading to diagnostic uncertainty in a clinical setting. A similar case may be classified as ET-plus by one observer and dystonic tremor by another. Following the new definition, many studies have reclassified their ET cohort, and they have highlighted the problem of defining questionable dystonia in the diagnosis of ET plus. ET-plus is likely to be a mixture of patients that actually have dystonia and those that don’t, and clinically all we can do is to be suspicious that there might be dystonia. For example, it is not clear whether we should consider spooning and index finger pointing as a sign of questionable or definite dystonia. There are major research and possible therapeutic implications of questionable dystonia in the diagnosis of ET-plus. The concept of ET-plus is extremely difficult to implement without definite guidelines. The resolution will need a biomarker such as physiology or imaging.

Movement Disorders in Genetic Pediatric Ataxias.

Genetic pediatric ataxias are heterogeneous rare disorders, mainly inherited as autosomal-recessive traits. Most forms are progressive and lack effective treatment, with relevant socioeconomical impact. Albeit ataxia represents the main clinical feature, the phenotype can be more complex, with additional neurological and nonneurological signs being described in several forms. In this review, we provide an overview of the occurrence and spectrum of movement disorders in the most relevant forms of childhood-onset genetic ataxias. All types of hypokinetic and hyperkinetic movement disorders of variable severity have been reported. Movement disorders occasionally represent the symptom of onset, predating ataxia even of a few years and therefore challenging an early diagnosis. Their pathogenesis still remains poorly defined, as it is not yet clear whether movement disorders may directly relate to the cerebellar pathology or result from an extracerebellar dysfunction, including the basal ganglia. Recognition of the complete movement disorder phenotype in genetic pediatric ataxias has important implications for diagnosis, management, and genetic counseling.

Essential tremor-plus: a controversial new concept.

In addition to redefining essential tremor (ET), the 2018 consensus statement of the Movement Disorder Society on tremor coined a new term: essential tremor-plus (ET-plus). This term is uncertainly defined as tremor with the characteristics of ET, with additional neurological signs of uncertain clinical significance. If ET-plus had been defined on the basis of a difference in underlying pathology or an appreciable difference in prognosis, it would have a valid, scientific rationale, as does the term Parkinson-plus. However, there is no such evidence, so the basis for the term is questionable. In fact, ET-plus might only represent a state condition (ie, patients with ET might develop these additional clinical features when the disease is at a more advanced stage). We caution against coining new terms that are not supported by a firm scientific basis and encourage research into the creation of essential tremor subsets that are defined with respect to differences in underlying causes or pathophysiology.