Olfactory Function in SCA10.

Although the main clinical manifestations of spinocerebellar ataxias (SCAs) result from damage of the cerebellum, other systems may also be involved. Olfactory deficits have been reported in other types of ataxias, especially in SCA3; however, there are no studies on olfactory deficits in SCA type 10 (SCA10). To analyze olfactory function of SCA10 patients compared with that of SCA3, Parkinson's, and healthy controls. Olfactory identification was tested in three groups of 30 patients (SCA10, SCA3, and Parkinson's disease (PD)) and 44 healthy controls using the Sniffin' Sticks (SS16) test. Mean SS16 score was 11.9 ± 2.9 for the SCA10 group, 12.3 ± 1.9 for the SCA3 group, 6.6 ± 2.8 for the PD group, and 12.1 ± 2.0 for the control group. Mean SS16 score for the SCA10 group was not significantly different from the scores for the SCA3 and control groups but was significantly higher than the score for the PD group (p < 0.001) when adjusted for age, gender, and history of smoking. There was no association between SS16 scores and disease duration in the SCA10 or SCA3 groups or number of repeat expansions. SS16 and Mini Mental State Examination scores were correlated in the three groups: SCA10 group (r = 0.59, p = 0.001), SCA3 group (r = 0.50, p = 0.005), and control group (r = 0.40, p = 0.007). We found no significant olfactory deficits in SCA10 in this large series.

Phenotypes, genotypes, and the management of paroxysmal movement disorders.

As a consequence of the genomic revolution, a large number of publications describing paroxysmal movement disorders have been published in the last few years, shedding light on their molecular pathology. Routine gene testing is not necessary to guide treatment for typical forms of paroxysmal kinesigenic dyskinesia (PKD), paroxysmal nonkinesigenic dyskinesia (PNKD), and episodic ataxia type 1 or 2. It can, however, be helpful in the management of atypical or complex cases, especially for genetic counselling, treatment strategies, and the offer of preimplantation genetic diagnosis. Antiepileptic drugs remain the treatment of choice for PKD and episodic ataxia type 1, benzodiazepines are often useful for PNKD, and episodic ataxia type 2 benefits from acetazolamide regardless of the genetic etiology. WHAT THE PAPER ADDS: A growing number of genes have been associated with classic and newly described paroxysmal movement disorders. Paroxysmal movement disorders share common mechanisms and clinical features with other neurological paroxysmal phenomena including epilepsy and migraine.

Nonmotor Symptoms in Patients with Spinocerebellar Ataxia Type 10.

Nonmotor symptoms (NMS) have been described in several neurodegenerative diseases but have not been systematically evaluated in spinocerebellar ataxia type 10 (SCA10). The objective of the study is to compare the frequency of NMS in patients with SCA10, Machado-Joseph disease (MJD), and healthy controls. Twenty-eight SCA10, 28 MJD, and 28 healthy subjects were prospectively assessed using validated screening tools for chronic pain, autonomic symptoms, fatigue, sleep disturbances, psychiatric disorders, and cognitive function. Chronic pain was present with similar prevalence among SCA10 patients and healthy controls but was more frequent in MJD. Similarly, autonomic symptoms were found in SCA10 in the same proportion of healthy individuals, while the MJD group had higher frequencies. Restless legs syndrome and REM sleep behavior disorder were uncommon in SCA10. The mean scores of excessive daytime sleepiness were worse in the SCA10 group. Scores of fatigue were higher in the SCA10 sample compared to healthy individuals, but better than in the MJD. Psychiatric disorders were generally more prevalent in both spinocerebellar ataxias than among healthy controls. The cognitive performance of healthy controls was better compared with SCA10 patients and MJD, which showed the worst scores. Although NMS were present among SCA10 patients in a higher proportion compared to healthy controls, they were more frequent and severe in MJD. In spite of these comparisons, we were able to identify NMS with significant functional impact in patients with SCA10, indicating the need for their systematic screening aiming at optimal treatment and improvement in quality of life.

Parkinson's disease without nigral degeneration: a pathological correlate of scans without evidence of dopaminergic deficit (SWEDD)?

OBJECTIVE: To describe 5 cases of Parkinson's disease lacking any detectable histopathology. BACKGROUND: The diagnosis of Parkinson's disease is supported histologically by the findings of α-synuclein immunopositive Lewy bodies and neurites and severe substantia nigra cell loss. Bradykinesia as defined by slowness of initiation of movement and a progressive reduction in speed and amplitude on finger tapping is a clinical correlate of pars compacta nigral degeneration. There are very few published cases of Parkinson's disease in which no pathological abnormality was found, and some of these cases were in hindsight thought to have probably been cases of indeterminate senile tremor or dystonic tremor. METHODS: Retrospective case notes review of the Queen Square Brain Bank archival collection and detailed neuropathological analysis of the selected cases. RESULTS: 5 cases considered to have Parkinson's disease by neurologists throughout the entirety of their illness that lacked any histopathological findings known to be associated with Parkinson's syndromes were identified out of a total number of 773 brains with a final clinical diagnosis of Parkinson's disease in the Queen Square Brain Bank. Retrospective case note analysis did not suggest dystonic tremor or indeterminate tremor in any of them. There was a reduction in tyrosine hydroxylase (TH) density in the striatum in these cases when compared with healthy controls, but not in the substantia nigra. CONCLUSIONS: Striatal dopamine deficiency without nigral cell loss is the most likely explanation for the clinical findings; other possible explanations include slowness due to comorbidities misinterpreted as bradykinesia, a tardive syndrome related to undisclosed previous neuroleptic exposure, or 'soft age-related' parkinsonian signs. These cases emphasise the need to regularly review the diagnosis in cases of suspected Parkinson's disease and highlight the need for precision in the neurological examination particularly of elderly patients. These cases may represent a distinct entity of diagnostic exclusion and may be considered one explanation for the radiological phenomenon of SWEDD (scans without evidence of dopaminergic deficit).

A field guide to current advances in paediatric movement disorders.

PURPOSE OF REVIEW: Recent advances in neurogenetics, neuroimmunology and nonpharmacological treatments have reshaped the field of paediatric movement disorders. In this review, we put recent findings into context providing a framework to enable navigation of the expanding literature in this field. RECENT FINDINGS: Anti-NMDA receptor encephalitis has proven to be a significant cause of treatable movement disorder in children and to present a multifaceted link with herpes simplex encephalitis. The growing use of next-generation sequencing in both research and clinical practice has unravelled an expanding number of genes related to paediatric movement disorders as well as expanding spectrums of variable expressivity and phenotypic pleiotropy for various genes. Behavioural therapies have been proven efficacious in Tourette's syndrome and are likely to be helpful in complex motor stereotypies. Management of dystonia remains a clinical priority and challenge. SUMMARY: The rapid advance of translational medicine has had major impacts on the field of paediatric movement disorders including diagnosis and treatment of these conditions.

PREDICT-PD: identifying risk of Parkinson's disease in the community: methods and baseline results.

OBJECTIVES: To present methods and baseline results for an online screening tool to identify increased risk for Parkinson's disease (PD) in the UK population. METHODS: Risk estimates for future PD were derived from the results of a systematic review of risk factors and early features of PD. Participants aged 60-80 years without PD were recruited by self-referral. They completed an online survey (including family history, non-motor symptoms and lifestyle factors), a keyboard-tapping task and the University of Pennsylvania Smell Identification Test. Risk scores were calculated based on survey answers. Preliminary support for the validity of this algorithm was assessed by comparing those estimated to be higher risk for PD with those at lower risk using proxies, including smell loss, REM-sleep behaviour disorder and reduced tapping speed, and by assessing associations in the whole group. RESULTS: 1324 eligible participants completed the survey and 1146 undertook the keyboard-tapping task. Smell tests were sent to 1065 participants. Comparing the 100 highest-risk participants and 100 lowest-risk participants, median University of Pennsylvania Smell Identification Test scores were 30/40 versus 33/40 (p<0.001), mean number of key taps in 30 s were 55 versus 58 (p=0.045), and 24% versus 10% scored above cut-off for REM-sleep behaviour disorder (p=0.008). Regression analyses showed increasing risk scores were associated with worse scores in the three proxies across the whole group (p≤0.001). CONCLUSIONS: PREDICT-PD is the first study to systematically combine risk factors for PD in the general population. Validity to predict risk of PD will be tested through longitudinal follow-up of incident PD diagnosis.

Pain and quality of life in athletes vs non-athletes with spinal cord injury: Observational study.

Spinal Cord Injuries (SCI) may cause non-motor symptoms, such as chronic pain, which impair quality of life (QoL)Objective: To investigate the relationship between adapted competitive sports, pain, and QoL in people with SCI in a limited resources setting population.Methods: This prospective cross-sectional observational study involved 16 athletes and 24 non-athletes with SCI and collected data on demographic and clinical variables including scores for pain and pain interference in daily life (Brief Pain Inventory, BPI), neuropathic pain severity (Neuropathic Pain Symptoms Inventory, NPSI) and Quality of life (Word Health Organization Quality of Life Assessment, WHOQOL-BREF). Non-parametric testing was used to compare the groups, and due to athletes being younger, multiple linear regression analyses were used to adjust for the effect of sports practice on the outcome variables when adjusting for age.Results: Athletes were younger (median age 36y) than non-athletes (median age 41.5y; Mann-Whitney U test P = 0.011), and QoL was superior in athletes for the Physical, Psychological, Social Relationships, Self-Evaluation domains, and Total Score when adjusted for age (P < 0.01). Despite having no significant differences in pain intensity scores (NPSI, P = 0.742 and BPI, P = 0.261) athletes had less pain interference on "Relationship with Others", "Enjoyment of Life", and Total score (P < 0.05). Participation in competitive adapted sports (P = 0.004) and Total Pain Interference (P = 0.043) were significantly associated with QoL scores in the multiple linear regression analyses.Conclusion: Athletes with SCI have better QoL and less pain interference in some aspects of life when compared to non-athletes.

The clinical diagnosis of Parkinson's disease.

After more than 200 years since its initial description, the clinical diagnosis of Parkinson's disease (PD) remains an often-challenging endeavor, with broad implications that are fundamental for clinical management. Despite major developments in understanding it's pathogenesis, pathological landmarks, non-motor features and potential paraclinical clues, the most accepted diagnostic criteria remain solidly based on a combination of clinical signs. Here, we review this process, discussing its history, clinical criteria, differential diagnoses, ancillary diagnostic testing, and the role of non-motor and pre-motor signs and symptoms.

Passados mais de 200 anos desde a sua descrição inicial, o diagnóstico clínico da doença de Parkinson (DP) continua a ser um processo muitas vezes desafiante, com amplas implicações que são fundamentais para o manejo clínico. Apesar dos grandes desenvolvimentos na compreensão da sua patogénese, marcadores patológicos, características não motoras e potenciais pistas paraclínicas, os critérios diagnósticos mais aceitos permanecem solidamente baseados numa combinação de sinais clínicos motores. Aqui, revisamos esse processo, discutindo sua história, critérios clínicos, diagnósticos diferenciais, testes diagnósticos complementares e o papel dos sinais e sintomas não motores e pré-motores.

Meta-analysis of early nonmotor features and risk factors for Parkinson disease.

OBJECTIVE: To evaluate the association between diagnosis of Parkinson disease (PD) and risk factors or early symptoms amenable to population-based screening. METHODS: A systematic review and meta-analysis of risk factors for PD. RESULTS: The strongest associations with later diagnosis of PD were found for having a first-degree or any relative with PD (odds ratio [OR], 3.23; 95% confidence interval [CI], 2.65-3.93 and OR, 4.45; 95% CI, 3.39-5.83) or any relative with tremor (OR, 2.74; 95% CI, 2.10-3.57), constipation (relative risk [RR], 2.34; 95% CI, 1.55-3.53), or lack of smoking history (current vs never: RR, 0.44; 95% CI, 0.39-0.50), each at least doubling the risk of PD. Further positive significant associations were found for history of anxiety or depression, pesticide exposure, head injury, rural living, beta-blockers, farming occupation, and well-water drinking, and negative significant associations were found for coffee drinking, hypertension, nonsteroidal anti-inflammatory drugs, calcium channel blockers, and alcohol, but not for diabetes mellitus, cancer, oral contraceptive pill use, surgical menopause, hormone replacement therapy, statins, acetaminophen/paracetamol, aspirin, tea drinking, history of general anesthesia, or gastric ulcers. In the systematic review, additional associations included negative associations with raised serum urate, and single studies or studies with conflicting results. INTERPRETATION: The strongest risk factors associated with later PD diagnosis are having a family history of PD or tremor, a history of constipation, and lack of smoking history. Further factors also but less strongly contribute to risk of PD diagnosis or, as some premotor symptoms, require further standardized studies to demonstrate the magnitude of risk associated with them.

Pisa syndrome in Parkinson's disease: a mobile or fixed deformity?

BACKGROUND: Although Pisa syndrome and scoliosis are sometimes used interchangeably to describe a laterally flexed postural deviation in Parkinson's disease (PD), the imaging findings of Pisa syndrome in PD have not been previously studied in detail. METHODS: Patients with PD and Pisa syndrome (lateral flexion >10° in the standing position) were examined clinically and underwent radiological assessment using standing radiograph and supine CT scan of the whole spine. RESULTS: Fifteen patients were included in this observational study. All patients had scoliosis on standing radiographs, and 12 had scoliosis persisting in the supine position. Scoliotic curves improved by a mean of 44% when patients moved from standing to supine. Only a quarter of patients with structural scoliosis had evidence of bony fusion on the side of their lateral deviation rendering their deformity fixed. CONCLUSIONS: Pisa syndrome describes a patient who lists to the side whereas scoliosis is defined by spinal curvature and rotation and may not be associated with lateral flexion. The finding of 'structural scoliosis' in Pisa syndrome should not preclude intervening to improve posture as most patients had little or no evidence of structural bony changes even when the deformity had been present for a number of years.

Demographic and motor features associated with the occurrence of neuropsychiatric and sleep complications of Parkinson's disease.

OBJECTIVE: To determine whether four key neuropsychiatric and sleep related features associated with Parkinson's disease (PD) are associated with the motor handicap and demographic data. BACKGROUND: The growing number of recognised non-motor features of PD makes routine screening of all these symptoms impractical. Here, we investigated the hypothesis that standard demographic data and the routine assessment of motor signs is associated with the presence of dementia, psychosis, clinically probable rapid eye movement (REM) sleep behavior disorder (cpRBD) and restless legs syndrome (RLS). METHODS: 775 patients with PD underwent standardised assessment of motor features and the presence of dementia, psychosis, cpRBD and RLS. A stepwise feature elimination procedure with fitted logistic regression models was applied to identify which/if any combination of demographic and motor factors is associated with each of the four studied non-motor features. A within-study out-of-sample estimate of the power of the predicted values of the models was calculated using standard evaluation procedures. RESULTS: Age and Hoehn&Yahr (H&Y) stage were strongly associated with the presence of dementia (p value<0.001 for both factors in the final selected model) while a combination of age, disease duration, H&Y stage, dopamine agonists and catechol-O-methyltransferase (COMT) inhibitors was associated with the presence of psychosis. Disease duration and H&Y stage were the significant indicators of cpRBD, and the lack of significant motor asymmetry was the only significant feature associated with RLS-type symptoms but the evidence of association was weak. CONCLUSIONS: Demographic and motor features routinely collected in patients with PD can estimate the occurrence of neuropsychiatric and sleep-related features of PD.

Clinical features of childhood-onset paroxysmal kinesigenic dyskinesia with PRRT2 gene mutations.

AIM: To define better the phenotype and genotype of familial and sporadic cases of paroxysmal kinesigenic dyskinesia (PKD) caused by mutations in the PRRT2 gene presenting in the paediatric age group. METHOD: We report the detailed clinical and molecular genetic features of 11 patients (six females, five males) with childhood-onset PRRT2-mutation-positive PKD. RESULTS: Mean age at disease onset was 8 years 7.5 months (range 5-11y), and clinical presentation was characterized by daily short paroxysmal episodes of dystonia/dyskinesia. Most patients also had non-kinesigenic attacks in addition to the classical movement-induced paroxysmal episodes. One family demonstrated great phenotypic variability with PKD, infantile convulsions, and/or hemiplegic migraine affecting different family members with the same mutation. All patients in whom antiepileptics (carbamazepine/phenytoin) were tried showed a dramatic improvement with complete abolition of dyskinetic episodes. INTERPRETATION: Our case series provides a detailed clinical description of patients with PRRT2-PKD, and reports a spectrum of disease-causing mutations, thereby expanding both the clinical phenotype and mutation spectrum of disease.

Pearls & Oy-sters: Paroxysmal Exercise-Induced Dyskinesias Due to Pyruvate Dehydrogenase Deficiency.

Paroxysmal exercise-induced movement disorders may be caused by energy metabolism disorders, such as Glut 1 deficiency, pyruvate dehydrogenase deficiency, or mitochondrial respiratory chain disorders. A 4-year-old boy with a history of febrile seizures presented with paroxysmal dystonia, triggered by exercise, or occurring at rest. Additional investigations demonstrated pallidal hyperintensities on brain MRI and low CSF glucose. Pyruvate and lactate were elevated. The clinical presentation combined with neuroimaging abnormalities and biochemical profile (the lactate/pyruvate ratio) were clues to pyruvate dehydrogenase deficiency, a treatable metabolic disorder with neurologic presentations.

Scoping Review on ADCY5-Related Movement Disorders.

Background: Adenylyl cyclase 5 (ADCY5)-related movement disorder (ADCY5-RMD) is a rare, childhood-onset disease resulting from pathogenic variants in the ADCY5 gene. The clinical features, diagnostic options, natural history, and treatments for this disease are poorly characterized and have never been established through a structured approach. Objective: This scoping review attempts to summarize all available clinical literature on ADCY5-RMD. Methods: Eighty-seven articles were selected for inclusion in this scoping review. The majority of articles identified were case reports or case series. Results: These articles demonstrate that patients with ADCY5-RMD suffer from permanent and/ or paroxysmal hyperkinetic movements. The paroxysmal episodes can be worsened by environmental triggers, in particular the sleep-wake transition phase in the early morning. Occurrence of nocturnal paroxysmal dyskinesias and perioral twitches are highly suggestive of the diagnosis when present. In the majority of patients intellectual capacity is preserved. ADCY5-RMD is considered a non-progressive disorder, with inter-individual variations in evolution with aging. Somatic mosaicism, mode of inheritance and the location of the mutation within the protein can influence phenotype. Conclusions: The current evidence for therapeutic options for ADCY5-RMD is limited: caffeine, benzodiazepines and deep brain stimulation have been consistently reported to be useful in case reports and case series.

Transitional Care for Young People with Movement Disorders: Consensus-Based Recommendations from the MDS Task Force on Pediatrics.

Background: The International Parkinson and Movement Disorders Society (MDS) set up a working group on pediatric movement disorders (MDS Task Force on Pediatrics) to generate recommendations to guide the transition process from pediatrics to adult health care systems in patients with childhood-onset movement disorders. Methods: To develop recommendations for transitional care for childhood onset movement disorders, we used a formal consensus development process, using a multi-round, web-based Delphi survey. The Delphi survey was based on the results of the scoping review of the literature and the results of a survey of MDS members on transition practices. Through iterative discussions, we generated the recommendations included in the survey. The MDS Task Force on Pediatrics were the voting members for the Delphi survey. The task force members comprise 23 child and adult neurologists with expertise in the field of movement disorders and from all regions of the world. Results: Fifteen recommendations divided across four different areas were made pertaining to: (1) team composition and structure, (2) planning and readiness, (3) goals of care, and (4) administration and research. All recommendations achieved consensus with a median score of 7 or greater. Conclusion: Recommendations on providing transitional care for patients with childhood onset movement disorders are provided. Nevertheless several challenges remain in the implementation of these recommendations, related to health infrastructure and the distribution of health resources, and the availability of knowledgeable and interested practitioners. Research on the influence of transitional care programs on outcomes in childhood onset movement disorders is much needed.

The clinical features of pathologically confirmed vascular parkinsonism.

OBJECTIVE: To evaluate in detail the clinical features in a large series of pathologically confirmed cases of vascular Parkinsonism (VP). BACKGROUND: In the absence of widely accepted diagnostic criteria for VP pathological confirmation of diagnosis is necessary to ensure diagnostic reliability, and has only been reported in a few small series. DESIGN/METHODS: The archival records of the Queen Square Brain Bank (QSBB) have been used to identify cases of Parkinsonism where cerebrovascular disease was the only pathological finding. Clinical notes were scrutinised and milestones of disease progression were compared with other atypical Parkinsonian syndromes from previous QSBB studies. RESULTS: Twenty-eight cases were included. Mean age of onset and disease duration were 70.6 (SD± 6.42) and 10.5 (SD± 66.1) years respectively. Bradykinesia was present in all cases, rigidity in 96%, falls in 76%, pyramidal signs in 54%, urinary incontinence in 50% and dementia in 39%.Visual hallucinations in 0%. Two-thirds had an insidious onset and a relentless rather than stepwise progression of disability. When compared with other Parkinsonian syndromes, VP had an older age of onset. CONCLUSIONS: In comparison with other Parkinsonian syndromes the patients were older and had an extremely low frequency of visual hallucinations compared with Parkinson's disease.

Olfactory impairment in familial ataxias.

The main clinical manifestations of the spinocerebellar ataxias (SCAs) result from the involvement of the cerebellum and its connections. Cerebellar activity has been consistently observed in functional imaging studies of olfaction, but the anatomical pathways responsible for this connection have not yet been elucidated. Previous studies have demonstrated olfactory deficit in SCA2, Friedreich's ataxia and in small groups of ataxia of diverse aetiology. The authors used a validated version of the 16-item smell identification test from Sniffin' Sticks (SS-16) was used to evaluate 37 patients with genetically determined autosomal dominant ataxia, and 31 with familial ataxia of unknown genetic basis. This data was also compared with results in 106 Parkinson's disease patients and 218 healthy controls. The SS-16 score was significantly lower in ataxia than in the control group (p<0.001, 95% CI for ß=0.55 to 1.90) and significantly higher in ataxia than in Parkinson's disease (p<0.001, 95% CI for ß=-4.58 to -3.00) when adjusted for age (p=0.001, 95% CI for ß=-0.05 to -0.01), gender (p=0.19) and history of tobacco use (p=0.41). When adjusted for general cognitive function, no significant difference was found between the ataxia and control groups. This study confirms previous findings of mild hyposmia in ataxia, and further suggests this may be due to general cognitive deficits rather than specific olfactory problems.

Is transcranial sonography useful to distinguish scans without evidence of dopaminergic deficit patients from Parkinson's disease?

BACKGROUND: Approximately 10% of patients clinically diagnosed with early Parkinson's disease (PD) subsequently have normal dopaminergic functional imaging. Transcranial sonography (TCS) has been shown to detect midbrain hyperechogenicity in approximately 90% of Parkinson's disease (PD) patients and 10% of the healthy population. The aim of this study was to investigate the prevalence of midbrain hyperechogenicity in patients with suspected parkinsonism and scans without evidence of dopaminergic deficit (SWEDD), in comparison to PD patients. METHODS: TCS was performed in 14 patients with SWEDD and 19 PD patients. RESULTS: There was a significantly increased area of echogenicity in the PD group (0.24 ± 0.06 cm(2) ), compared to the group of patients with SWEDD (0.13 ± 0.06 cm(2) ; P < 0.001). One (9.1%) of these patients, compared to 14 (82.5%) of the PD patients, was found to have hyperechogenicity (P < 0.001). CONCLUSIONS: We conclude that TCS is useful to distinguish PD patients from patients with suspected parkinsonism and SWEDD.

Globular glial tauopathies (GGT) presenting with motor neuron disease or frontotemporal dementia: an emerging group of 4-repeat tauopathies.

A number of recent studies have described cases with tau-positive globular oligodendroglial inclusions (GOIs) and such cases have overlapping pathological features with progressive supranuclear palsy (PSP), but present with clinical features of motor neuron disease (MND) and/or frontotemporal dementia (FTD). These two clinical phenotypes have been published independently and as a result, have come to be considered as distinct disease entities. We describe the clinicopathological and biochemical features of two cases with GOIs: one with clinical symptoms suggestive of MND and the other with FTD. Histological changes in our two cases were consistent with their clinical symptoms; the MND case had severe neurodegeneration in the primary motor cortex and corticospinal tract, whereas the FTD case had severe involvement of the frontotemporal cortices and associated white matter. Immunohistochemistry in both cases revealed significant 4-repeat (4R) tau pathology primarily in the form of GOIs, but also in astrocytes and neurons. Astrocytic tau pathology was morphologically similar to that seen in PSP, but in contrast was consistently negative for Gallyas silver staining. Tau-specific western blotting revealed 68, 64 and 35 kDa bands, showing further overlap with PSP. The underlying neuropathological features of these two cases were similar, with the major difference relating to the regional distribution of pathology and resulting clinical symptoms and signs. The globular nature of glial inclusions and the non-fibrillar properties of tau in astrocytes are characteristic features that allow them to be distinguished from PSP and other tauopathies. We, therefore, propose the term globular glial tauopathy as an encompassing term to classify this emerging class of 4R tauopathy.