General Neurology
Metal neurotoxicity
Nov. 05, 2024
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Progressive supranuclear palsy (PSP) …
- Updated 06.19.2024
- Released 04.10.1993
- Expires For CME 06.19.2027
Progressive supranuclear palsy
Introduction
Overview
Progressive supranuclear palsy is a late-onset degenerative disease of the central nervous system characterized by balance difficulties, vertical gaze palsy, dysarthria, dysphagia, and axial dystonia. Pathologic findings include neurofibrillary degeneration of extrapyramidal neurons. It remains an intractable and underrecognized neurodegenerative illness with a median survival of only seven years. However, patients will benefit from accurate, early diagnosis that allows them to understand the prognosis, to avoid unnecessary tests and useless treatments, and to avail themselves of disease-specific support services. Advances in understanding the tau protein aggregation and mitochondrial dysfunction of progressive supranuclear palsy and the toxic and genetic insults underlying them are accruing swiftly. In this article, the author describes the subtypes of progressive supranuclear palsy as well as advances in pathology, imaging, and genetics of the disorder.
Key points
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• Ophthalmoparesis, especially downgaze impairment, is a classic clinical feature of progressive supranuclear palsy that may appear later in the course of the disorder. | |
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• Slowing of downward saccades appears earlier in the clinical course of progressive supranuclear palsy. | |
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• Multiple subtypes of progressive supranuclear palsy have been identified, including the classic Richardson syndrome, progressive supranuclear palsy-parkinsonism (PSP-P), or pure-akinesia-with-gait-freezing (PAGF). |
Historical note and terminology
The first complete clinicopathologic description of progressive supranuclear palsy was published in 1964 (146). However, there were 13 earlier clinical cases in the literature, six with autopsy (19). Some of these antedate the 1920s epidemic of postencephalitic parkinsonism, suggesting that progressive supranuclear palsy is not a variant of that condition despite their pathological similarity (20). The meticulously described motor disorder of a character in an 1857 Dickens novel is a convincing picture of progressive supranuclear palsy (88). Since the early 1960s when many astute movement disorder specialists were unable to recall having seen progressive supranuclear palsy, this disorder has become commonly recognized at movement disorder referral centers, comprising 4% to 5% of their cases of parkinsonism (46).
Monographs (93; 19) and a layperson's guide (44) are available. Lay organizations were founded in the United States in 1990 (The Society for Progressive Supranuclear Palsy) and in Europe in 1994 (The Progressive Supranuclear Palsy (PSP-Europe) Association).
Clinical manifestations
Presentation and course
Progressive supranuclear palsy is often initially misdiagnosed as Parkinson disease for at least the first 3 or 4 years after onset. Like Parkinson disease, it results in rigidity, bradykinesia, postural instability, dysarthria, dysphagia, and, in many cases, dementia. Unlike Parkinson disease, however, there rarely is tremor; postural instability is an early rather than later symptom; rigidity is worse at the neck than in the limbs; dysarthria is spastic, ataxic, and hypophonic rather than purely hypophonic (101; 77); dysphagia may be more symptomatic than in Parkinson disease because of its prominent oral component (143). Ling and colleagues showed micrographia without decrementing amplitude and lack of decrementing amplitude on finger taps progressive supranuclear palsy patients compared to Parkinson disease patients (92). Disease progression causes reduction of horizontal and vertical saccade amplitudes in progressive supranuclear palsy, but not Parkinson disease patients (148).
The most frequent initial symptom is postural instability, often taking the form of unheralded falls that prompt a workup for vestibulopathy, syncope, basilar ischemia, or epilepsy. This symptom usually remains the most disabling feature of progressive supranuclear palsy. The next most frequent presenting feature is mental disturbance in the form of personality change, emotional incontinence, or depression. Consequently, the first medical contact is sometimes a psychiatrist (46). The dementia is usually frontal in quality (49). One sign of frontal lobe dysfunction typically present in progressive supranuclear palsy is the “applause sign” (“signe de l’applaudissment”). This probably represents perseveration of automatic behavior (37). Patients with higher degrees of frontal lobe dysfunction exhibit the “jumping the gun” sign, which is defined as premature initiation of clapping before the start signal from the examiner (04). Purposeless groaning has also been reported in progressive supranuclear palsy (99). Sleep disturbances are disabling for some patients (05).
The best-known feature of progressive supranuclear palsy, but one that may be late or not obvious, is impairment of ocular gaze, particularly in the downward direction.
A highly common early finding is slowing of downward saccades, which remain normal in amplitude until later in the course. Frequent associated ocular findings are horizontal square-wave jerks, slow and hypometric saccades, and paresis of upward gaze (122; 149). Impairment of downward opticokinetic nystagmus can help distinguish progressive supranuclear palsy from Parkinson disease (42). Lateral gaze paresis may occur late. Zwergal and colleagues show slower progression of horizontal gaze paresis compared to vertical and range of ocular motility in smooth pursuit decrease of 1.5 mm/year on upgaze, 1.6 mm/year on downgaze, and 1.4 mm/year on horizontal gaze (171).
"Apraxia" of lid movement and blepharospasm are common and the blink rate averages three to five per minute (normal 20 to 30 per minute) (45).
Approximately one third of patients with pathologically proven progressive supranuclear palsy present with relative asymmetry, tremor, and a useful, if transient, levodopa response that often prompts a diagnosis of Parkinson disease. Williams and colleagues named this variant “progressive supranuclear palsy-parkinsonism” (PSP-P) and the classic syndrome that comprises about half of all progressive supranuclear palsy patients, “Richardson syndrome” (PSP-RS) (163). The Richardson disease variant displays greater intensity of tau pathology than the progressive supranuclear palsy-parkinsonism (PSP-P) or pure-akinesia-with-gait-freezing (PAGF) variants (166). PAGF presents with early gait disturbance, micrographia, hypophonia, and eventual gait freezing (165). In studies of PAGF patients, severe atrophy has been found only in the globus pallidus, substantia nigra, and subthalamic nucleus (165). Progressive supranuclear palsy with corticobasal syndrome and progressive supranuclear palsy with speech apraxia have also been reported (89). PSP-pallido-nigro-luysian atrophy (PSP-PNLA) cases typically present younger and with earlier gait impairment, but later dysphagia than PSP-RS (03). A syndrome with falls, cerebellar ataxia, and supranuclear gaze palsy without dysautonomia has been proposed as progressive supranuclear palsy with predominant cerebellar ataxia (PSP-C) (72). Additional nonmotor symptoms are present in progressive supranuclear palsy. Sleep and mood issues, urinary frequency, nocturia, and constipation were reported in a study of 50 consecutive progressive supranuclear palsy patients (124). Cognitive dysfunction is also present and is associated with severity of progressive supranuclear palsy-related tau pathology (79). Apraxia of speech may be an early sign of progressive supranuclear palsy, but it can also be present in other disorders, such as corticobasal syndrome (121). Protracted coursed progressive supranuclear palsy (PC-PSP) has been described with an 11-year-old clinical course (40).
The diagnosis is typically first suspected by a physician noticing poor levodopa response and vertical gaze restriction in a parkinsonian patient. Clues that may aid earlier diagnosis are spastic or ataxic speech, contracted facies, slow downward saccades (albeit with normal amplitude at first), erect or hypererect posture, and a disorganized, ataxic-appearing gait with falls early in the disease course. In a study of 339 not demented progressive supranuclear palsy patients meeting the NINDS-SPSP, 221 of whom were considered “frequent fallers”, symptom duration, clinical measures of disease severity, and several motoric and oculomotor clinical parameters were associated with frequent falls (12).
Clinical presentation of corticobasal syndrome may be due to progressive supranuclear palsy pathology, and is termed PSP-CBS. More cortical tau burden in PSP-CBS corresponds with clinical findings of corticobasal syndrome such as apraxia (91). In addition, corticobasal degeneration pathology may present as a PSP clinical diagnosis (CBD-PSPS). Clinical progressive supranuclear palsy syndrome (PSPS) correlates with midbrain atrophy. Patients with progressive supranuclear palsy pathology but without PSPS did not have appreciable midbrain atrophy (160). Diffusion tensor imaging of nine CBS subjects (unknown pathology) compared to 18 probable or definite PSP cases, nine of whom were pathologically confirmed, showed more symmetric degeneration in PSP with more degeneration of the superior cerebellar peduncle and midbrain (162). The phenotypic spectrum of progressive supranuclear palsy is enlarging, with individual case reports of cerebellar ataxia and orthostatic hypotension in pathologically confirmed progressive supranuclear palsy.
MDS-PSP diagnostic criteria published by Hoglinger and colleagues include four domains (oculomotor dysfunction, postural instability, akinesia, and cognitive dysfunction), with levels of certainty based on clinical findings in each domain, for example, vertical supranuclear gaze palsy being more certain than slowing of vertical saccade velocity (62).
Prognosis and complications
The median interval from onset of the initial symptom, regardless of its nature, to onset of gait difficulty is 0.3 years; to the need for gait assistance, 3.1 years; dysarthria, 3.4 years; visual symptoms, 3.9 years; dysphagia 4.4 years; and death 7.3 years (46; 47). The problems that most frequently cause complications or death are falls and dysphagia with aspiration.
Clinical vignette
A 66-year-old woman began to experience diplopia and suffered one fall while running on uneven ground. Within the next few months, she acquired a staring expression, nonfluency of speech, a sustention tremor of both hands, and she suffered two more falls. One year after onset, she consulted a neurologist, who found square-wave jerks, slow and hypometric saccades with slowing worse in the downward direction, limitation of upgaze but not downgaze, mild rigidity at the wrists, wide-based gait, and a tendency to retropulse. MRI was normal. The diplopia responded modestly to prisms. Treatment with carbidopa and levodopa 25/100 four times daily gave no benefit, caused mouth dryness, and was subsequently reduced to three times daily. Amantadine 100 mg twice a day and sertraline at an unknown dosage gave no benefit or adverse effects.
Three years after onset, the patient was suffering from moderate social withdrawal, mild dysphagia for both fluids and solids (which had to be cut into small pieces), slowness in all manual activities, at least one fall per day if she walked unassisted, consistent urinary incontinence, and both primary and secondary insomnia. Examination revealed normal orientation and memory, mild bradyphrenia, a moderate degree of frontal behavioral disturbance, contracted facies, reduction of saccadic amplitudes (up, 5 degrees; down, 20 degrees; right, 35 degrees; left, 40 degrees) (normal is 50 degrees in each direction), frequent, large-amplitude square-wave jerks, inhibition of lid closing, mild spastic dysarthria, slowed swallowing of water with no aspiration, moderate neck rigidity, symmetric limb rigidity, slowing of distal rapid alternating movements, mild sustention tremor of the right hand, wide-based irregular gait requiring occasional reliance on walls or furniture, and an inability to recover from the pull test. The score on the PSP Rating Scale (0=normal, 100=worst possible) was 46.
Titration of carbidopa and levodopa to 1500 mg (of levodopa) per day gave no benefit and caused fatigue. Oxybutynin 5 mg twice daily helped the incontinence transiently. Amitriptyline titrated to 50 mg twice daily helped the balance and speech markedly for 4 or 5 weeks, when those symptoms returned to baseline. Confusion occurred two months later and the amitriptyline was tapered and discontinued with return of mentation to baseline and no worsening of gait.
Over the following year, the PSP Rating Scale score progressed gradually to 65, with progression of the frontal behavior, loss of all command eye movement, immobility of the neck to active and passive movement, and a need for major assistance in gait. There was only mild progression of dysphagia and no worsening of limb rigidity. Three months later, six years after symptom onset, the patient developed pneumonia and sepsis and died.
Brain autopsy showed neurofibrillary tangles 4+ in the subthalamic nucleus; 3+ in the striatum, globus pallidus, substantia nigra, locus ceruleus, and pontine base; 2+ in premotor and motor cortex, nucleus basalis, ventral thalamus, oculomotor nucleus, periaqueductal gray, medullary tegmentum, inferior olive, and cerebellar dentate; and 1+ in temporal cortex, red nucleus, and raphe nuclei. Neuronal loss was most marked in the subthalamic nucleus and in the ventral and lateral tier of the substantia nigra; it was moderate in the ventral and lateral thalamus. These changes are typical of progressive supranuclear palsy.
Biological basis
Etiology and pathogenesis
One case-control study failed to find any premorbid correlates of progressive supranuclear palsy among the many risk factors that have been associated with, or suspected of association with, other neurodegenerative disease (34), but another study found an association with lower educational attainment (48). The island of Guam in the Pacific and Guadeloupe in the Caribbean each harbors a cluster of patients with a different progressive supranuclear palsy-like disorder (24; 145). There have been no clear occupational or temporal clusters of progressive supranuclear palsy, but seven autopsy-proven familial clusters from five countries have been reported (128). Relatives of patients with progressive supranuclear palsy are more likely than controls to have parkinsonian signs or symptoms (34).
Further evidence for a genetic etiologic component is a well confirmed but weak association of the disease with the H1 haplotype of the gene for tau (30; 09; 57), a protein that forms abnormal intracellular aggregates in progressive supranuclear palsy.
Progressive supranuclear palsy is one of the tauopathies. The pathologic hallmarks are neuronal loss, gliosis, and flame-shaped and globose neurofibrillary tangles (NFT) composed of paired helical filaments and straight filaments of tau protein (68; 55). The tangles are similar to those in Alzheimer disease, but the tau protein consists almost solely of an isoform with four repeating copies of the microtubule-binding domain (4R-tau), rather than the 1:1 ratio of 3-repeat (3R-tau) and 4-repeat isoforms occurring in Alzheimer disease and in normals (25). Intronic variant rs564309 minor allele A in tripartite motif containing 11 (TRIM11) has been found to be associated with neurofibrillary tangles and is less common in PSP-RS than other phenotypic variants (151). In addition to NFT pathology, increased levels of phosphorylated and unphosphorylated tau oligomers have been demonstrated by Gerson and colleagues (43). Alternative splicing of the MAPT gene leads to expression of different tau isoforms. 4R-tau results from inclusion of exon 10 (100). Smith reports that microRNA-132 loss is associated with abnormal splicing of exon 10 (140). microRNA-132 appears to affect the neuronal splicing factor PTBP2 leading to imbalance in the 4R-tau to 3R-tau ratio. Six Japanese patients with early-onset progressive supranuclear palsy were found to have MAPT p.S285R mutations (115).
Progressive supranuclear palsy exhibits no amyloid deposition or apolipoprotein E allelic association (07). There is evidence that mitochondrial genetic defects (147), abnormal oxidation (29), and inappropriate transglutamination (75) contribute to the tau aggregation and cellular loss.
In a genome-wide association study, Jabbari and colleagues found a possible survival benefit with rs2242367, which affects levels of LRRK2 expression (65). Further research in model systems is needed to confirm the clinical relevance of this finding (28).
Phosphorylation is important for regulation of tau binding to microtubules and affects the association of tau with plasma membranes and nuclei. Glycogen synthase kinase-3 (GSK-3) mediated tau phosphorylation may play a role in pathogenesis of tauopathies. For example, axonal damage and motor impairment resulting from 4R tau overexpression in a mouse model is ameliorated with GSK-3beta expression (54).
The damage is greatest and most consistent in the substantia nigra, subthalamic nucleus, globus pallidus, superior colliculus, pretectal area, and substantia innominata (01). Cortical neuronal involvement has been documented (55), and thalamic relays to cortex have been found to be involved (56). Red nucleus, medulla, and dentate nucleus involvement has also been reported (165). In both PSP-P and Richardson syndrome, damage to subthalamic nucleus and substantia nigra are greatest. Less severe damage to parts of the midbrain other than substantia nigra in PSP-P may contribute to presence of tremor and moderate levodopa responsiveness in this variant (165). Temporal lobe structures with connections to the superior colliculus are involved with generation of the classic side-to-side movement seen with fixation termed “square wave jerks” (02). Kovacs and colleagues propose a sequential model of neuronal tau pathology spread in progressive supranuclear palsy (84). According to their model, neuronal tau pathology starts in the subthalamic nucleaus, substantia nigra, and globus pallidus and spreads to the midbrain and pons. The next step would be to the cerebellum and amygdala, followed by the frontal lobe, the parietal and temporal lobes, and, finally, the occipital lobe.
Dopaminergic, cholinergic, GABAergic, and adrenergic neurotransmitter systems are affected. The poor levodopa responsiveness may be the result of loss of cholinergic interneurons in the striatum, onto which synapse the dopaminergic terminals of the nigrostriatal tract, or of the internal segment of the globus pallidus, the major outflow from the basal ganglia. However, this explanatory model has been called into question (157). Mean cortical acetylcholinesterase activity was shown to be significantly reduced in progressive supranuclear palsy as compared to controls (59). Dementia Rating Scale impairment was seen in 57% of a group of 311 progressive supranuclear palsy patients, indicating a high level of cognitive dysfunction in this disorder (18). Mild deficits in autobiographical memory without temporal gradient were found in progressive supranuclear palsy patients, indicating a likely frontal retrieval deficit (169).
The first transgenic animal model of progressive supranuclear palsy has appeared (90). A toxin model using intravenous annonacin, a component of the tropical fruits associated with the progressive supranuclear palsy-like illness on Guadeloupe, has been reported (26).
Genetics. The H1 haplotype of the tau gene on chromosome 17q21 (93.7% vs. 78.4%) and the H1/H1 genotype (87.5% vs. 62.8%) are overrepresented to a modest but statistically significant degree in patients with progressive supranuclear palsy compared to controls (09). Both H1 and H1/H1 are also overrepresented in corticobasal degeneration (63) and, to a slightly lesser degree, in Parkinson disease. Patients with progressive supranuclear palsy who are H1/H2 heterozygotes may display a lesser tau burden at autopsy than H1/H1 homozygotes (164). However, the Richardson disease and progressive supranuclear palsy-parkinsonism phenotypes do not differ with regard to H1 haplotype frequency (166). The H1c haplotype, which is more specifically associated with progressive supranuclear palsy than other H1 subhaplotypes, increases expression of tau, especially of the 4-repeat variant, which includes the product of exon 10, the location of one of the microtubule-binding repeat domains (23; 108). Patients homozygous for the H1 haplotype may have earlier onset age, according to one study, but apolipoprotein E status has no effect on the disease course despite its effect on Alzheimer disease (08).
Although the tau mutations in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) affect microtubule binding domains of the C-terminus of the tau protein, the progressive supranuclear palsy variants affect domains that interact with the neural plasma membrane. FTDP-17 is a primary tauopathy with overlap of pathological features with progressive supranuclear palsy, Alzheimer disease, corticobasal degeneration, and Pick disease (165). Clinically typical progressive supranuclear palsy is most likely associated with the tau progressive supranuclear palsy susceptibility genotype (H1/H1) and doublet tau protein pattern (64 and 69kDa) (107). The pathogenic effect of the H1 haplotype may be a simple overexpression of tau protein via a variant in the tau promoter that is part of the haplotype (87). Or the pathogenic locus may exist at a distance from the tau gene itself, as the H1 haplotype includes multiple flanking genes in 5’ and 3’ directions (117). One promising lead is that a single base substitution in a regulatory region of the tau gene has been found to be the statistically most critical variant in the H1 haplotype (123). Although progressive supranuclear palsy is almost always sporadic, rare families with the phenotype have been reported, a few of which have point mutations in the tau gene, similar to families with frontotemporal dementia linked to chromosome 17. Zhao and colleagues propose that apoptosin-mediated caspase cleavage of tau plays a role in the pathogenesis of progressive supranuclear palsy (170). Imaging studies with 18F-AV-1451 radioligand for tau do not reflect the tau pathology of progressive supranuclear palsy in cortex and white matter, perhaps due to decreased tau burden relative to Alzheimer disease and less binding to 4R filaments. There is increased basal ganglia binding of this radioligand, but it is unclear if this is true tau pathology or off target binding (120; 142). In later studies, 18F-AV-1451 (also named 18F-T807 or 18F-Flortaucipir) was able to differentiate between progressive supranuclear palsy and Alzheimer disease pathology (141).
A genome-wide association study found increased risk of progressive supranuclear palsy associated with eukaryotic translation initiation factor 2-alpha kinase 3 (EIF2AK3), myelin-associated oligodendrocyte basic protein (MOBP), and syntaxin-6 (STX6) as well as variants of the gene coding for tau protein (61). A genome-wide association study by Chen and colleagues confirmed association with chromosome 17 at or near the MAPT gene (27). A metaanalysis by the same authors confirmed association of rs1768208 polymorphism of the MOBP gene with progressive supranuclear palsy (27). This polymorphism was associated with white matter variance in the midbrain and superior longitudinal fasciculus in sporadic frontotemporal lobar degeneration cases (106). In another genome-wide association study involving 152 corticobasal degeneration cases and 3311 controls, and 67 corticobasal degeneration cases and 439 controls in a replication stage, an association was found with MAPT at 17q21 (which codes for tau protein) and with MOBP at 3p22 (which codes for MOBP) (82). The authors concluded that corticobasal degeneration and progressive supranuclear palsy share a genetic risk factor at these two loci.
Linkage to 1q31.1 has been demonstrated in one large Spanish family (129). Another locus, at chromosome 11p11-p12, has been incriminated by pooled genome-wide analysis. The two leading candidate genes in that interval participate in DNA repair and in lysosomal function (103). Increased risk of progressive supranuclear palsy and corticobasal degeneration has been reported with VEGF mutations (14).
STX6, EIF2AK3, and MOBP genes on chromosomes 1, 2, and 3, respectively, have been implicated by genome wide association studies, but direct coding changes in these genes could not be identified (39). Sanchez-Contreras and colleagues confirmed these GWAS associations and included SLCO1A2 (rs11568563) and DUSP10 (rs6687758) (131).
An unusual case of familial PSP-P phenotype was identified with sequence variants in the FBXO7 and VPS35 genes and neuropathology consistent with Braak stage VI Parkinson disease as opposed to the classic tau pathology (105). The patient had poor response to levodopa. However, the authors also describe that the patient had hallucinations requiring quetiapine, which is not classic for PSP (10). Given that hallucinations were found by a different group in a VPS35 carrier (139), clinically and pathologically this case may perhaps be viewed as PARK17 parkinsonism with hallucinations as opposed to PSP-P.
A single case of simultaneous presentation of progressive supranuclear palsy and behavior variant of frontotemporal dementia was reported due to a sporadic mutation in the progranulin (GRN) gene (c.1498G> A, p.V500I) (35).
Epidemiology
Two separate surveys in the United Kingdom found the age-adjusted prevalence of progressive supranuclear palsy to be approximately 5 per 100,000 population, about 3% to 5% of the prevalence of Parkinson disease (136; 109). Men appear to be slightly more frequently affected than women. Approximately half of the patients with progressive supranuclear palsy experience the initial symptoms during their 60s, with one fourth each in their 50s and 70s (101; 46). However, the age-specific incidence is highest in the oldest measurable decades (15).
Differential diagnosis
Parkinson disease is the condition most frequently confused with progressive supranuclear palsy. Its variant, dementia with Lewy bodies, can resemble progressive supranuclear palsy, but with more dementia. The combination of frequent square-wave jerks and low blink rate may provide a clinically convenient distinction of progressive supranuclear palsy from Parkinson disease (06). Multiple system atrophy, parkinsonian type (formerly known as “striatonigral degeneration”), usually has less vertical gaze palsy and more dysautonomia than progressive supranuclear palsy (76), but a case report of pathologically confirmed progressive supranuclear palsy with dysautonomia has been presented (104). A multi-infarct state (167) would feature vascular abnormalities on MRI and usually pyramidal signs or focal cortical deficits. Corticobasal degeneration is far more asymmetric than progressive supranuclear palsy and exhibits more apraxia and cortical sensory loss. Patients with progressive supranuclear palsy pathology at autopsy have been described to have clinically manifest corticobasal syndrome (PSP-CBS) (91).
Less important considerations that can mimic progressive supranuclear palsy, particularly by virtue of producing vertical gaze palsy, are multiple system atrophy, the parkinsonism-dementia-amyotrophic complex of Guam, Whipple disease, neuroacanthocytosis, progressive external ophthalmoplegia, and hydrocephalus. For patients with only bulbar signs, myasthenia gravis or motor neuron disease should be considered. Dorsal midbrain mass lesion from cysticercosis may approximate some features of progressive supranuclear palsy including gaze palsy and falls (138). A progressive supranuclear palsy-like phenotype has also been reported with hypoxia (74). In addition to the choreic phenotype, Niemann Pick disease type C may have a phenotype consisting of ataxia and supranuclear gaze palsy, which may be confused with progressive supranuclear palsy (85).
One progressive supranuclear palsy–like phenotype that is increasingly recognized is anti-IgLON5 disease (41; 50). This autoimmune disorder associated with anti-IgLON5 antibodies is characterized by a complex sleep disorder, rapid periodic leg movements during wakefulness that may briefly continue following sleep onset, cognitive decline, severe gait instability, chorea predominantly affecting the limbs (also orofacial dyskinesia), and oculomotor dysfunction similar to that observed in patients with progressive supranuclear palsy. At autopsy these patients may have characteristic aggregates of tau protein in the tegmentum and brainstem. Patients with this disorder respond poorly to immunosuppressive therapy and may die of sudden death during sleep or wakefulness. It appears that the IgLON5 autoantibodies are directed predominantly against brainstem and hypothalamic neurons.
Diagnostic workup
Clinical diagnostic criteria have been formulated using a large autopsy series (94). Beyond a careful physical examination, MR imaging is the only workup required for most people suspected to have progressive supranuclear palsy. MRI’s principal goal is to rule out a multi-infarct state or hydrocephalus. Midbrain atrophy disproportionate to that of the pons or cerebellum is a specific but not a highly sensitive sign of supranuclear palsy (134; 132; 31). According to Massey and colleagues, sagittal midbrain measurement of <9.35 mm and midbrain to pontine base ratio of 0.52 provided 100% specificity for progressive supranuclear palsy, as opposed to multiple system atrophy, Parkinson disease, or normal controls (102). A study of 23 PSP-RS patients and 42 Parkinson disease patients found 99% diagnostic accuracy when differentiating these disorders via midbrain area (168). The marked midbrain atrophy when viewed on sagittal MRI suggests the image of a “penguin” or of a “hummingbird” (114; 97; 161). Clinical decline is correlated with frontal lobe and midbrain atrophy (71). Primary progressive apraxia of speech was noted to have midbrain atrophy, but milder than in progressive supranuclear palsy, suggesting a possible relationship between the disorders (159).
Disproportionate atrophy of the superior cerebellar peduncle on MRI can also help distinguish progressive supranuclear palsy from its close mimics, including multiple system atrophy (118). In addition, there are differences in superior cerebellar peduncle imaging between PSP-RS and PSP-PD. An automated system to analyze the superior cerebellar peduncle has been proposed (110). An “eye-of-the-tiger” sign, high T2 signal in a V formed by the lateral and medial putamen with normal signal between them, occurs in a minority of patients (132). Diffusion tensor imaging (DTI) evaluation of progressive supranuclear palsy versus controls reveals sensitive (0.92) and specific (1.0) differences in radial diffusivity in the superior cerebellar peduncle (78). This is in contrast to middle cerebellar peduncle and pontine crossing tract DTI changes in moderate to advanced MSA (113). Interestingly, the apparent diffusion coefficient MRI sequence has been reported to show increased signal in the middle cerebellar peduncle of progressive supranuclear palsy that is absent in MSA of the parkinsonian type and in other progressive supranuclear palsy mimics (119). However, another study shows that Richardson syndrome has been found to have statistically significant differences in average apparent diffusion coefficient (ADCave) values in the superior cerebellar peduncle on magnetic resonance imaging as compared to Parkinson disease and healthy volunteers (126). Whitwell and colleagues demonstrated disruption of thalamic connectivity with superior cerebellar peduncle degeneration in progressive supranuclear palsy, likely due to dentatorubrothalamic tract degeneration (158). Mean diffusivity in the vermis is higher in patients with PSP-RS, as opposed to patients with Parkinson disease or healthy subjects. Evaluation of mean diffusivity in the entire cerebellar hemisphere via median values allows for differentiation between multiple system atrophy and PSP-RS (111).
Both SPECT (51) and PET using deoxyglucose (17) show prefrontal hypoactivity in progressive supranuclear palsy. PET imaging of dopaminergic terminals shows severe involvement of the caudate and putamen in progressive supranuclear palsy, but relative sparing the caudate in Parkinson disease (22). Tau-PET tracers (F-FDG and F-THK5351) have been used on a research basis (98). Magnetic resonance spectroscopy of the lentiform nuclei can distinguish progressive supranuclear palsy from normal and from Parkinson disease (33). Transcranial 2-D ultrasound has been reported to discriminate progressive supranuclear palsy, which displays hyperechogenicity of globus pallidus but not substantia nigra, from Parkinson disease, where the opposite pattern occurs (156; 155). However, it has not been established that any of these tests can more accurately distinguish early or equivocal progressive supranuclear palsy from its mimics than can a good history and neurologic examination. Early (first 10 minutes) perfusion dominant imaging with F-FP-CIT PET (pCIT) may provide discrimination between Parkinson disease and progressive supranuclear palsy additional to classic dopamine transporter imaging (69). The PET ligand [18F]-AV-1451 has shown abnormal binding in bilateral pallidum and rostral interstitial nucleus of the medial longitudinal fasciculus in a case report of a single patient with clinical diagnosis of Richardson syndrome (53). 11C-pyridinyl-butadienyl-benzothiazole 3 (C-PBB3) positron emission tomography may help in differentiating between progressive supranuclear palsy and corticobasal syndrome as well as Alzheimer disease (135).
The pontine nuclei, dentate nucleus, and cerebellum are less affected in PAGF as compared to Richardson syndrome. Functional scans reveal normal frontal lobe metabolism in PAGF (165). Diffusion tensor imaging (DTI) shows diffuse involvement of the thalamus in progressive supranuclear palsy, most prevalent in the anterior aspect, including the anterior and medial nuclei. In corticobasal degeneration, there is asymmetric involvement of the motor thalamus (38). DTI also shows inferior fronto-occipital fasciculus changes in progressive supranuclear palsy patients, especially those with severe frontal cognitive symptoms versus controls (86).
A clinical syndrome of corticobasal degeneration may be due to progressive supranuclear palsy pathology (PSP-CBS) (70). Corticobasal degeneration pathology, in turn, may cause a Richardson syndrome phenotype (83). Postural instability occurs later than in Richardson syndrome (154). Progressive non-fluent aphasia may also be due to progressive supranuclear palsy pathology (70).
The Progressive Supranuclear Palsy Rating Scale (PSPRS) can monitor the clinical state and provide prognostic information (47). A copy is available at the following website: http://www.psp.org. A neural network model of PSPRS and Unified Parkinson Disease Rating Scale (UPDRS) data found individual scale items that were associated with frequent fallers and may be amenable to rehabilitation or other interventions. These include PSPRS arising from chair, gait, and sitting down parameters (11).
A clinical scale measuring quality-of-life is also now available (137).
Biomarker research shows lower CSF N-terminal and C-terminal tau protein concentrations in progressive supranuclear palsy compared to normal controls and Alzheimer disease (153). Decreased p-tau levels and CSF neurofilament light chain are being investigated as biomarkers for progressive supranuclear palsy (64). Skin biopsy and evaluation with antibodies for phosphorylated tau are also being investigated (127). Volumetric MRI changes correlate with disease progression (150).
Management
Drug treatment of progressive supranuclear palsy remains unsatisfactory (81). There is no disease-modifying therapy, but one longitudinal study suggested a potential protective role of lifetime estrogen exposure (116). Levodopa ameliorates the bradykinesia and rigidity in about one third of cases but the benefit rarely persists beyond 1 or 2 years (66; 67; 112). Patients with progressive supranuclear palsy are relatively resistant to dopaminergic motor and psychiatric side effects, so large dosages (up to 2000 mg per day, with decarboxylase inhibitor) are usually well tolerated and are worth a trial. Levodopa improved dysphagia in a series of three patients (152).
Amitriptyline and amantadine can ameliorate certain deficits in progressive supranuclear palsy, but anticholinergic side effects often limit their use and adequate controlled trials are lacking (112). Centrally acting cholinergic medication, despite the profound cholinergic deficit in progressive supranuclear palsy, has been disappointing or deleterious (96; 95). Behavioral issues such as apathy and impulsivity can exist in up to two thirds of patients (80). Behavioral symptoms and impaired activities of daily living were the main drivers of caregiver burden in progressive supranuclear palsy (73).
A speech pathologist can help manage the dysphagia and perhaps institute a communication method for dysarthric patients. Feeding gastrostomy should be considered after the first confirmed episode of frank aspiration or of aspiration pneumonitis, if the patient requires more time to finish a meal than the household can practically provide, if there is significant weight loss because of reduced intake, or if a minor degree of aspiration occurs with every mouthful.
Rehabilitation strategies for progressive supranuclear palsy have been proposed, but no outcome data are available on more than one or two patients in any protocol, and no crossover or parallel control data are available. It is important to modify the home environment to reduce the potential injury from falls. Electroconvulsive therapy, adrenal striatal implantation, and pallidotomy are of no benefit. Blepharospasm responds well to botulinum toxin injection, and dry eyes from infrequent blink can be treated with topical lubricants. Botulinum toxin injections into neck flexor muscles for torticollis dystonia are inadvisable because of the risk of exacerbating the dysphagia, but injection into the extensor muscles for disabling retrocollis is often successful. Deep brain stimulation surgery of the pedunculopontine nucleus has been tried with some success in small, open-label case series (36), but unilateral surgery did not improve balance or falls in a prospective trial with patients randomly assigned to 1-week blocks of stimulation ON or OFF settings in a double-blind fashion (133).
Clinical trials of disease-modifying therapy included the glycogen synthase kinase 3 beta (GSK3b) inhibitor and tideglusib (NP-12) (13). Tideglusib failed to meet the Tauros clinical trial primary end point of improvement in overall clinical status, but there is reduction of global brain atrophy on this treatment (60). Lithium was not tolerated, but sodium valproate continues to be investigated in progressive supranuclear palsy for its GSK-3 inhibition. Unfortunately, trials of riluzole and rasagiline were unsuccessful (125). Tau aggregation inhibitor davunetide, an 8 amino acid peptide, failed to show neuroprotection in progressive supranuclear palsy. There was no improvement in progressive supranuclear palsy rating scale or Schwab and England Activities of Daily Living (SEADL) scale over placebo in the davunetide study (16). A subgroup analysis of patients in the davunetide study looking at amantadine showed a potential benefit on SEADL, which became statistically nonsignificant after correcting for age, baseline PSPRS, and coenzyme Q10 use (58). The authors suggested a study to specifically analyze amantadine in progressive supranuclear palsy. Pyruvate, creatine, and niacinamide are being studied to address mitochondrial dysfunction (144). Research therapies aimed at tau have not been successful (32).
Open label cerebellar transcranial magnetic stimulation with intermittent theta burst improved cerebellar functional connectivity as measured by resting state fMRI (21). A standardized progressive supranuclear palsy rating scale (PSPRS) has been developed to increase consistency in clinical studies (52).
Special considerations
Pregnancy
No cases of progressive supranuclear palsy during pregnancy have been reported.
Anesthesia
Patients with any form of parkinsonism should avoid neuroleptic tranquilizers. The dysphagia of progressive supranuclear palsy dictates special precautions against aspiration. The retrocollis of progressive supranuclear palsy may narrow the airway, requiring tracheostomy for intubation (130).
Media
References
- 01
- Agid Y, Javoy-Agid F, Ruberg M, et al. Progressive supranuclear palsy: anatomo-clinical and biochemical considerations. Adv Neurol 1987;45:191-206. PMID 2881445
- 02
- Anagnostou E, Karavasilis E, Potiri I, et al. A cortical substrate for square-wave jerks in progressive supranuclear palsy. J Clin Neurol 2020;16(1):37-45. PMID 31942756
- 03
- Ahmed Z, Josephs KA, Gonzalez J, DelleDonne A, Dickson DW. Clinical and neuropathologic features of progressive supranuclear palsy with severe pallido-nigro-luysial degeneration and axonal dystrophy. Brain 2008;131(Pt 2):460-72. PMID 18158316
- 04
- Ahn JH, Kwon J, Won JH, et al. Waiting impulsivity in progressive supranuclear palsy-Richardson's syndrome. Front Neurosci 2023;17:1240709. PMID 37817800
- 05
- Aldrich MS, Foster NL, White RF, Bluemlein L, Prokopowicz G. Sleep abnormalities in progressive supranuclear palsy. Ann Neurol 1989;25:577-81. PMID 2742360
- 06
- Altiparmak UE, Eggenberger E, Coleman A, Condon K. The ratio of square wave jerk rates to blink rates distinguishes progressive supranuclear palsy from Parkinson disease. J Neuroophthalmol 2006;26:257-9. PMID 17204917
- 07
- Anouti A, Schmidt K, Lyons KE, et al. Normal distribution of apolipoprotein E alleles in progressive supranuclear palsy. Neurology 1996;46:1156-7. PMID 8780111
- 08
- Baba Y, Putzke JD, Tsuboi Y, et al. Effect of MAPT and APOE on prognosis of progressive supranuclear palsy. Neurosci Lett 2006;405:116-9. PMID 16839689
- 09
- Baker M, Litvan I, Houlden H, et al. Association of an extended haplotype in the tau gene with progressive supranuclear palsy. Hum Mol Genet 1999;8(4):711-5. PMID 10072441
- 10
- Bartonikova T, Mensikova K, Mikulicova L, et al. Familial atypical parkinsonism with rare variant in VPS35 and FBXO7 genes: a case report. Medicine (Baltimore) 2016;95(46):e5398. PMID 27861377
- 11
- Bluett B, Litvan I, Cheng S, et al. Understanding falls in progressive supranuclear palsy. Parkinsonism Relat Disord 2017;35:75-81. PMID 28007518
- 12
- Bluett B, Litvan I, Cheng S, et al. Understanding, predicting, and preventing falls in progressive supranuclear palsy [abstract]. Mov Disord 2016;31(suppl 2).
- 13
- Boeve BF. Progressive supranuclear palsy. Parkinsonism Relat Disord 2012;18 Suppl 1):S192-4. PMID 22166432
- 14
- Borroni B, Del Bo R, Goldwurm S, et al. VEGF haplotypes are associated with increased risk to progressive supranuclear palsy and corticobasal syndrome. J Alzheimers Dis 2010;21:87-94. PMID 20413880
- 15
- Bower JH, Maraganore DM, McDonnell SK, Rocca WA. Incidence of progressive supranuclear palsy and multiple system atrophy in Olmsted County, Minnesota, 1976 to 1990. Neurology 1997;49:1284-8. PMID 9371909
- 16
- Boxer AL, Lang AE, Grossman M, et al. Davunetide in patients with progressive supranuclear palsy: a randomised, double-blind, placebo-controlled phase 2/3 trial. Lancet Neurol 2014;13(7):676-85. PMID 24873720
- 17
- Brooks DJ. Positron emission tomographic studies of the subcortical degenerations and dystonia. Semin Neurol 1989;9:351-9. PMID 2701780
- 18
- Brown RG, Lacomblez L, Landwehrmeyer BG, et al. Cognitive impairment in patients with multiple system atrophy and progressive supranuclear palsy. Brain 2010;133(Pt 8):2382-93. PMID 20576697
- 19
- Brusa A, Peloso PF. An introduction to progressive supranuclear palsy. Rome: John Libby, 1993.
- 20
- Brusa A, Stoehr R, Pramstaller PP. Progressive supranuclear palsy: new disease or variant of postencephalitic parkinsonism. Mov Disord 2004;19:247-52. PMID 15022178
- 21
- Brusa L, Ponzo V, Mastropasqua C, et al. Theta burst stimulation modulates cerebellar-cortical connectivity in patients with progressive supranuclear palsy. Brain Stimul 2014;7(1):29-35. PMID 23928103
- 22
- Burn DJ, Sawle GV, Brooks DJ. Differential diagnosis of Parkinson disease, multiple system atrophy, and Steele-Richardson-Olszewski syndrome: discriminant analysis of striatal 18F-dopa PET data. J Neurol Neurosurg Psychiatry 1994;57:278-84. PMID 8158173
- 23
- Caffrey TM, Joachim C, Paracchini S, Esiri MM, Wade-Martins R. Haplotype-specific expression of exon 10 at the human MAPT locus. Hum Mol Genet 2006;15:3529-37. PMID 17085483
- 24
- Caparros-Lefevbre D, Elbaz A. Possible relation of atypical parkinsonism in the French West Indies with consumption of tropical plants: a case-control study. Lancet 1999;354:281-6. PMID 10440304
- 25
- Chambers CB, Lee JM, Troncoso JC, Reich S, Muma NA. Overexpression of four-repeat tau mRNA isoforms in progressive supranuclear palsy but not in Alzheimer's disease. Ann Neurol 1999;46:325-32. PMID 10482263
- 26
- Champy P, Höglinger GU, Feger J, et al. Annonacin, a lipophilic inhibitor of mitochondrial complex I, induces nigral and striatal neurodegeneration in rats: possible relevance for atypical parkinsonism in Guadeloupe. J Neurochem 2004;88:63-9. PMID 14675150
- 27
- Chen Z, Shatunov A, Bensimon G, et al. A genome-wide association study in progressive supranuclear palsy. J Neurol Neurosurg Psychiatry 2015;86:e4.
- 28
- Chen-Plotkin AS. LRRK2 and survival in progressive supranuclear palsy. Lancet Neurol 2021;20(2):83-4. PMID 33341148
- 29
- Chirichigno JW, Manfredi G, Beal MF, Albers DS. Stress-induced mitochondrial depolarization and oxidative damage in PSP cybrids. Brain Res 2002;951(1):31-5. PMID 12231453
- 30
- Conrad E, Andreadis A, Trojanowski JQ, et al. Genetic evidence for the involvement of tau in progressive supranuclear palsy. Ann Neurol 1997;41:277-81. PMID 9029080
- 31
- Cosottini M, Ceravolo R, Faggioni L, et al. Assessment of midbrain atrophy in patients with progressive supranuclear palsy with routine magnetic resonance imaging. Acta Neurol Scand 2007;116:37-42. PMID 17587253
- 32
- Coughlin DG, Litvan I. Investigational therapeutics for the treatment of progressive supranuclear palsy. Expert Opin Investig Drugs 2022;31(8):813-23. PMID 35695010
- 33
- Davie CA, Barker, GJ, Machado C, Miller DH, Lees AJ. Proton magnetic resonance spectroscopy in Steele-Richardson-Olszewski syndrome. Mov Disord 1997;12:767-71. PMID 9380064
- 34
- Davis PH, Golbe LI, Duvoisin RC, Schoenberg BS. Risk factors for progressive supranuclear palsy. Neurology 1988;38:1546-52. PMID 3419596
- 35
- Deng B, Zheng Z, Zheng J, et al. FTD-PSP is an unusual clinical phenotype in a frontotemporal dementia patient with a novel progranulin mutation. Aging Dis 2021;12(7):1741-52. PMID 34631218
- 36
- Doshi PK, Desai JD, Karkera B, Wadia PM. Bilateral pedunculopontine nucleus stimulation for progressive supranuclear palsy. Stereotact Funct Neurosurg 2015;93(1):59-65. PMID 25662728
- 37
- Dubois B, Slachevsky A, Pillon B, Beato R, Villalponda JM, Litvan I. “Applause sign” helps to discriminate PSP from FTD and PD. Neurology 2005;64(12):2132-3. PMID 15985587
- 38
- Erbetta A, Mandelli ML, Savoiardo M, et al. Diffusion tensor imaging shows different topographic involvement of the thalamus in progressive supranuclear palsy and corticobasal degeneration. Am J Neuroradiol 2009;30:1482-7. PMID 19589886
- 39
- Ferrari R, Ryten M, Simone R, et al. Assessment of common variability and expression quantitative trait loci for genome-wide associations for progressive supranuclear palsy. Neurobiol Aging 2014;35(6):1514.e1-12. PMID 24503276
- 40
- Forrest SL, Tartaglia MC, Kim A, Alcaide-Leon P, Rogaeva E, Lang A, Kovacs GG. Progressive supranuclear palsy syndrome associated with a novel tauopathy: case study. Neurology 2022;99(24):1094-8. PMID 36192179
- 41
- Gaig C, Graus F, Compta Y, et al. Clinical manifestations of the anti-IgLON5 disease. Neurology 2017;88(18):1736-43. PMID 28381508
- 42
- Garbutt S, Riley DE, Kumar AN, Han Y, Harwood MR, Leigh RJ. Abnormalities of optokinetic nystagmus in progressive supranuclear palsy. J Neurol Neurosurg Psychiatry 2004;75:1386-94. PMID 15377682
- 43
- Gerson JE, Sengupta U, Lasagna-Reeves CA, Guerrero-Munoz MJ, Troncoso J, Kayed R. Characterization of tau oligomeric seeds in progressive supranuclear palsy. Acta Neuropathol Commun 2014;2:73. PMID 24927818
- 44
- Golbe LI. Progressive supranuclear palsy--some answers: a guide for patient and family. 7th ed. Baltimore: Society for Progressive Supranuclear Palsy, 2006.
- 45
- Golbe LI, Davis PH, Lepore FE. Eyelid movement abnormalities in progressive supranuclear palsy. Mov Disord 1989;4:297-302. PMID 2811889
- 46
- Golbe LI, Davis PH, Schoenberg BS, Duvoisin RC. Prevalence and natural history of progressive supranuclear palsy. Neurology 1988;38:1031-4. PMID 3386818
- 47
- Golbe LI, Ohman-Strickland PA. A clinical rating scale for progressive supranuclear palsy. Brain 2007;130:1552-65. PMID 17405767
- 48
- Golbe LI, Rubin RS, Cody RP, et al. Follow-up study of risk factors in progressive supranuclear palsy. Neurology 1996;47:148-54. PMID 8710069
- 49
- Grafman J, Litvan I, Gomez C, Chase TN. Frontal lobe function in progressive supranuclear palsy. Arch Neurol 1990;47:553-8. PMID 2334303
- 50
- Graus F, Santamaría J. Understanding anti-IgLON5 disease. Neurol Neuroimmunol Neuroinflamm 2017;4(5):e393. PMID 28852690
- 51
- Habert MO, Spampinato U, Mas JL, et al. A comparative technetium 99m hexamethylpropylene amine oxime SPET [sic] study in different types of dementia. Eur J Nucl Med 1991;18:3-11. PMID 2019279
- 52
- Hall DA, Stebbins GT, Litvan I, et al. Clinimetric analysis of the motor section of the progressive supranuclear palsy rating scale: reliability and factor analysis. Movmnt Disords Clncl Practice 2015;3(1):65-7. PMID 30363575
- 53
- Hammes J, Bischof G, Giehl K, et al. Elevated in vivo [18F]-AV-1451 uptake in a patient with progressive supranuclear palsy. Mov Disord 2017;32(1):170-1. PMID 27476874
- 54
- Hanger DP, Noble W. Functional implications of glycogen synthase kinase-3-mediated tau phosphorylation. Int J Alzheimers Dis 2011;2011:352805. PMID 21776376
- 55
- Hauw JJ, Daniel SE, Dickson D, et al. Preliminary NINDS neuropathologic criteria for Steele-Richardson-Olszewski syndrome (progressive supranuclear palsy). Neurology 1994;44:2015-9. PMID 7969952
- 56
- Henderson JM, Carpenter K, Cartwright H, Halliday GM. Loss of thalamic intralaminar nuclei in progressive supranuclear palsy and Parkinson’s disease: clinical and therapeutic implications. Brain 2000;123(Pt 7):1410-21. PMID 10869053
- 57
- Higgins JJ, Adler RL, Loveless JM. Mutational analysis of the tau gene in progressive supranuclear palsy. Neurology 1999;53:421-4. PMID 10534245
- 58
- Hiller A, Murchison C, Nichols J, Quinn J. The effects of amantadine on the progression of Progressive Supranuclear Palsy (PSP) (P6.068). Neurology 2018;90(15 Supplement).
- 59
- Hirano S, Shintotoh H, Shimada H, et al. Cholinergic imaging in corticobasal syndrome, progressive supranuclear palsy and frontotemporal dementia. Brain 2010;133:2058-68. PMID 20558417
- 60
- Hoglinger G, Huppertz H, Wagenpfeil S, et al. Tideglusib, a GSK-3 inhibitor, reduces progression of brain atrophy in progressive supranuclear palsy. Basal Ganglia 2013;3(1):47-8.
- 61
- Hoglinger GU, Melhem NM, Dickson DW, et al. Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy. Nat Genet 2011;43:699-705. PMID 21685912
- 62
- Hoglinger GU, Respondek G, Stamelou M, et al. Clinical diagnosis of progressive supranuclear palsy: the movement disorder society criteria. Mov Disord 2017;32(6):853-64. PMID 28467028
- 63
- Houlden H, Baker M, Morris HR, et al. Corticobasal degeneration and progressive supranuclear palsy share a common tau haplotype. Neurology 2001;56:1702-6. PMID 11425937
- 64
- Ichikawa-Escamilla E, Velasco-Martínez RA, Adalid-Peralta L. Progressive supranuclear palsy syndrome: an overview. IBRO Neurosci Rep 2024;16:598-608. PMID 38800085
- 65
- Jabbari E, Koga S, Valentino R. Genetic determinants of survival in progressive supranuclear palsy: a genome-wide association study. Lancet Neurol 2021;20(2):107-16. PMID 33341150
- 66
- Jackson JA, Jankovic J, Ford J. Progress supranuclear palsy: clinical features and response to treatment in 16 patients. Ann Neurol 1983;13:273-8. PMID 6847139
- 67
- Jankovic J. Progressive supranuclear palsy: clinical and pharmacologic update. Neurol Clin 1984;2:473-86. PMID 6398402
- 68
- Jellinger K, Riederer P, Tomonaga M. Progressive supranuclear palsy: clinico-pathological and biochemical studies. J Neural Transm Suppl 1980;16:111-28. PMID 6107328
- 69
- Jin S, Oh M, Oh SJ, et al. Additional value of early-phase 18F-FP-CIT PET image for differential diagnosis of atypical parkinsonism. Clin Nucl Med 2017;42(2):e80-e87. PMID 27922865
- 70
- Josephs KA, Petersen RC, Knopman DS, et al. Clinicopathologic analysis of frontotemporal and corticobasal degenerations and PSP. Neurology 2006;66:41-8. PMID 16401843
- 71
- Josephs KA, Xia R, Mandrekar J, et al. Modeling trajectories of regional volume loss in progressive supranuclear palsy. Mov Disord 2013;28(8):1117-24. PMID 23568852
- 72
- Kanazawa M, Tada M, Onodera O, Takahashi H, Nishizawa M, Shimohata T. Early clinical features of patients with progressive supranuclear palsy with predominant cerebellar ataxia. Parkinsonism Relat Disord 2013;19(12):1149-51. PMID 23916652
- 73
- Kellermair L, Fuchs A, Eggers C, et al. Caregiver strain in progressive supranuclear palsy and corticobasal syndromes. J Neural Transm (Vienna) 2021;128(10):1611-21. PMID 34296340
- 74
- Kim HT, Shields S, Bhatia KP, Quinn N. Progressive supranuclear palsy-like phenotype associated with bilateral hypoxic-ischemic striopallidal lesions. Mov Disord 2005;20: 55-7. PMID 15782420
- 75
- Kim SY, Jeiter TM, Steinert PM. Transglutaminases in disease. Neurochem Int 2002;40:85-103. PMID 11738475
- 76
- Kimber J, Mathias CJ, Lees AJ, et al. Physiological, pharmacological and neurohormonal assessment of autonomic function in progressive supranuclear palsy. Brain 2000;123:1422-30. PMID 10869054
- 77
- Kluin KJ, Foster NL, Berent S, Gilman S. Perceptual analysis of speech disorders in progressive supranuclear palsy. Neurology 1993;43:563-6. PMID 8451002
- 78
- Knake S, Belke M, Menzler K, et al. In vivo demonstration of microstructural brain pathology in progressive supranuclear palsy: a DTI study using TBSS. Mov Disord 2010;25(9):1232-8. PMID 20222139
- 79
- Koga S, Parks A, Kasanuki K, et al. Cognitive impairment in progressive supranuclear palsy is associated with tau burden. Mov Disord 2017;32(12):1772-79. PMID 29082658
- 80
- Kok ZQ, Murley AG, Rittman T, et al. Co-occurrence of apathy and impulsivity in progressive supranuclear palsy. Mov Disord Clin Pract 2021;8(8):1225-33. PMID 34761056
- 81
- Kompoliti K, Goetz CG, Litvan I, Jellinger K, Verny M. Pharmacological therapy in progressive supranuclear palsy. Arch Neurol 1998;55:1099-102. PMID 9708960
- 82
- Kouri N, Ross OA, Dombroski B, et al. Genome-wide association study of corticobasal degeneration identifies risk variants shared with progressive supranuclear palsy. Nat Commun 2015;6:7247. PMID 26077951
- 83
- Kouri N, Whitwell JL, Josephs KA, Rademakers R, Dickson DW. Corticobasal degeneration: a pathologically distinct 4R tauopathy. Nat Rev Neurol 2011;7(5):263-72. PMID 21487420
- 84
- Kovacs GG, Lukic MJ, Irwin DJ, et al. Distribution patterns of tau pathology in progressive supranuclear palsy. Acta Neuropathol 2020;140(2):99-119. PMID 32383020
- 85
- Kresojevic N, Mandić-Stojmenović G, Dobričić V, et al. Very late-onset Niemann Pick type C disease: example of progressive supranuclear palsy look-alike disorder. Mov Disord Clin Pract 2020;7(2):211-4. PMID 32071943
- 86
- Kvickstrom P, Eriksson B, van Westen D, Latt J, Elfgren C, Nilsson C. Selective frontal neurodegeneration of the inferior fronto-occipital fasciculus in progressive supranuclear palsy (PSP) demonstrated by diffusion tensor tractography. BMC Neurol 2011;11:13. PMID 21269463
- 87
- Kwok JB, Teber ET, Loy C, et al. Tau haplotypes regulate transcription and are associated with Parkinson's disease. Ann Neurol 2004;55(3):329-34. PMID 14991810
- 88
- Larner AJ. Did Charles Dickens describe progressive supranuclear palsy in 1857. Mov Disord 2002;17:832-3. PMID 12210887
- 89
- Levy R. Progressive supranuclear palsy: what’s new. Geriatr Psychol Neuropsychiatr Vieil 2011;9:191-201. PMID 21690028
- 90
- Lewis J, McGowan E, Rockwood J, et al. Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice expressing mutant (P301L) tau protein. Nat Genet 2000;25:402-5. PMID 10932182
- 91
- Ling H, de Silva R, Massey LA, et al. Characteristics of progressive supranuclear palsy presenting with corticobasal syndrome: a cortical variant. Neuropathol Appl Neurobiol 2014;40(2):149-63. PMID 23432126
- 92
- Ling H, Massey LA, Lees AJ, Brown P, Day BL. Hypokinesia without decrement distinguishes progressive supranuclear palsy from Parkinson's disease. Brain 2012;135(Pt 4):1141-53. PMID 22396397
- 93
- Litvan I, Agid Y, editors. Progressive supranuclear palsy. New York: Oxford, 1992.
- 94
- Litvan I, Agid Y, Calne D, et al. Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome): report of the NINDS-SPSP international workshop. Neurology 1996;47:1-9. PMID 8710059
- 95
- Litvan I, Blesa R, Clark K, et al. Pharmacological evaluation of the cholinergic system in progressive supranuclear palsy. Ann Neurol 1994;36:55-61. PMID 8024262
- 96
- Litvan I, Gomez C, Atack JR, et al. Physostigmine treatment of progressive supranuclear palsy. Ann Neurol 1989;26:404-7. PMID 2802540
- 97
- Longoni G, Agosta F, Kostić VS, et al. MRI measurements of brainstem structures in patients with Richardson's syndrome, progressive supranuclear palsy-parkinsonism, and Parkinson's disease. Mov Disord 2011;26(2):247-55. PMID 21412831
- 98
- Lopez-Mora DA, Fernández León A, Lleó A, Blesa R, Camacho V. The added value of Tau-PET in the assessment of progressive supranuclear palsy. Clin Nucl Med 2020;45(5):e239-40. PMID 32149810
- 99
- Low SC, Tan AH, Lim SY. Teaching video neuroimages: purposeless groaning in progressive supranuclear palsy. Neurology 2017;88(1):e9. PMID 28025406
- 100
- Luk C, Vandrovcova J, Malzer E, et al. Brain tau isoform mRNA and protein concentration in PSP brain. Translational Neurosci 2010;1:30-6.
- 101
- Maher ER, Lees AJ. The clinical features and natural history of the Steele-Richardson-Olszewski syndrome (progressive supranuclear palsy). Neurology 1986;36:1005-8. PMID 3714047
- 102
- Massey LA, Jager HR, Paviour DC, et al. The midbrain to pons ratio: a simple and specific MRI sign of progressive supranuclear palsy. Neurology 2013;80(20):1856-61. PMID 23616165
- 103
- Melquist S, Craig DW, Huentelman MJ, et al. Identification of a novel risk locus for progressive supranuclear palsy by a pooled genomewide scan of 500,288 single-nucleotide polymorphisms. Am J Hum Genet 2007;80:769-78. PMID 17357082
- 104
- Mensikova K, Tuckova L, Ehrmann J, Kanovsky P. Unusual phenotype of pathologically confirmed progressive supranuclear palsy with autonomic dysfunction and cerebellar ataxia: case report. Medicine (Baltimore) 2016;95(46):e5237. PMID 27861346
- 105
- Mensikova K, Tuckova L, Kolarikova K, et al. Atypical parkinsonism of progressive supranuclear palsy-parkinsonism (PSP-P) phenotype with rare variants in FBXO7 and VPS35 genes associated with Lewy body pathology. Acta Neuropathol 2019;137(1): 171-3. PMID 30374525
- 106
- McMillan CT, Toledo JB, Avants BB, et al. Genetic and neuronanatomic associations in sporadic frontotemporal lobar degeneration. Neurobiol Aging 2014;35(6):1473-82. PMID 24373676
- 107
- Morris HR, Gibb G, Katzenschlager R, et al. Pathological, clinical and genetic heterogeneity in progressive supranuclear palsy. Brain 2002;125(Pt 5):969-75. PMID 11960887
- 108
- Myers AJ, Pittman AM, Zhao AS, et al. The MAPT H1c risk haplotype is associated with increased expression of tau and especially of 4 repeat containing transcripts. Neurobiol Dis 2007;25:561-70. PMID 17174556
- 109
- Nath U, Ben-Shlomo Y, Thomson RG, et al. The prevalence of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome) in the UK. Brain 2001;124(Pt 7):1438-49. PMID 11408338
- 110
- Nicoletti G, Caligiuri ME, Cherubini A, et al. A fully automated, atlas-based approach for superior cerebellar peduncle evaluation in progressive supranuclear palsy phenotypes. AJNR Am J Neuroradiol 2017;38(3):523-30. PMID 28034996
- 111
- Nicoletti G, Rizzo G, Barbagallo G, et al. Diffusivity of cerebellar hemispheres enables discrimination of cerebellar or parkinsonian multiple system atrophy from progressive supranuclear palsy-Richardson syndrome and Parkinson disease. Radiology 2013;267(3):843-50. PMID 23329659
- 112
- Nieforth KA, Golbe LI. Retrospective study of drug response in 87 patients with progressive supranuclear palsy. Clin Neuropharmacol 1993;16:338-46. PMID 8374914
- 113
- Nilsson C, Markenroth Bloch K, Brockstedt S, Latt J, Widner H, Larsson EM. Tracking the neurodegeneration of parkinsonian disorders – a pilot study. Neuroradiology 2007;49(2):111-9. PMID 17200869
- 114
- Oba H, Yagishita A, Terada H, et al. New and reliable MRI diagnosis for progressive supranuclear palsy. Neurology 2005;64:2050-5. PMID 15985570
- 115
- Ogaki K, Li Y, Takanashi M, et al. Analyses of the MAPT, PGRN, and C9orf72 mutations in Japanese patients with FTLD, PSP, and CBS. Parkinsonism Relat Disord 2013;19(1):15-20. PMID 22818528
- 116
- Park HK, Ilango S, Charriez CM, et al. Lifetime exposure to estrogen and progressive supranuclear palsy: ENGENE-PSP study. Mov Disord 2018;33(3):468-72. PMID 29460982
- 117
- Pastor P, Ezquerra M, Perez JC, et al. Novel haplotypes in 17q21 are associated with progressive supranuclear palsy. Ann Neurol 2004;56(2):249-58. PMID 15293277
- 118
- Paviour DC, Price SL, Stevens JM, Lees AJ, Fox NC. Quantitative MRI measurement of superior cerebellar peduncle in progressive supranuclear palsy. Neurology 2005;64:675-9. PMID 15728291
- 119
- Paviour DC, Thornton JS, Lees AJ, Jager HR. Diffusion-weighted magnetic resonance imaging differentiates Parkinsonian variant of multiple-system atrophy from progressive supranuclear palsy. Mov Disord 2007;22:68-74. PMID 17089396
- 120
- Perez-Soriano A, Stoessl AJ. Tau imaging in progressive supranuclear palsy. Mov Disord 2017;32(1):91-3. PMID 27862260
- 121
- Peterson KA, Patterson K, Rowe JB. Language impairment in progressive supranuclear palsy and corticobasal syndrome. J Neurol 2021;268(3):796-809. PMID 31321513
- 122
- Pfaffenbach DD, Layton DD, Kearns TP. Ocular manifestations in progressive supranuclear palsy. Am J Ophthalmol 1972;74:1179-84. PMID 4646725
- 123
- Rademakers R, Melquist S, Cruts M, et al. High-density SNP haplotyping suggests altered regulation of tau gene expression in progressive supranuclear palsy. Hum Mol Genet 2005;14:3281-92. PMID 16195395
- 124
- Radicati FG, Martinez Martin P, Fossati C, et al. Non motor symptoms in progressive supranuclear palsy: prevalence and severity. NPJ Parkinsons Dis 2017;3:35. PMID 29238748
- 125
- Rittman T, Rowe JB. What’s new in progressive supranuclear palsy. ACNR 2012;11(6):8-10.
- 126
- Rizzo G, Martinelli P, Manners D, et al. Diffusion-weighted brain imaging study of patients with clinical diagnosis of corticobasal degeneration, progressive supranuclear palsy and Parkinson's disease. Brain 2008;131:2690-700. PMID 18819991
- 127
- Rodriguez-Leyva I, Calderon-Garcidueñas A, Santoyo M, Chi E, Medina-Mier V, Jimenez-Capdeville M. Progressive supranuclear palsy (PSP): diagnosis through skin biopsy (P1.014). Neurology 2014;82(10):Suppl P1.014.
- 128
- Rojo A, Pernaute RS, Fontan A, et al. Clinical genetics of familial progressive supranuclear palsy. Brain 1999;122:1233-45. PMID 10388790
- 129
- Ros R, Gomez Garre P, Hirano M, et al. Genetic linkage of autosomal dominant progressive supranuclear palsy to 1q31.1. Ann Neurol 2005;57:634-41. PMID 15852377
- 130
- Sakai K, Sumikawa K. Anesthetic management of a patient with progressive supranuclear palsy. J Anesth 2006;20:312-3. PMID 17072698
- 131
- Sanchez-Contreras MY, Kouri N, Cook CN, et al. Replication of progressive supranuclear palsy genome-wide association study identifies SLCO1A2 and DUSP10 as new susceptibility loci. Mol Neurodegener 2018;13(1):37. PMID 29986742
- 132
- Savoiardo M, Strada L, Girotti F, et al. MR imaging in progressive supranuclear palsy and Shy-Drager syndrome. J Comput Assist Tomogr 1989;13:555-60. PMID 2745772
- 133
- Scelzo E, Lozano AM, Hamani C, et al. Peduncolopontine nucleus stimulation in progressive supranuclear palsy: a randomised trial. J Neurol Neurosurg Psychiatry 2017;88(7):613-6. PMID 28214797
- 134
- Schonfeld SM, Golbe LI, Safer J, Sage JI, Duvoisin RC. Computed tomographic findings in progressive supranuclear palsy: correlation with clinical grade. Mov Disord 1987;2:263-78. PMID 3504554
- 135
- Schroter N, Blazhenets G, Frings L, et al. Tau imaging in the 4-repeat-tauopathies progressive supranuclear palsy and corticobasal syndrome: a 11C-pyridinyl-butadienyl-benzothiazole 3 PET pilot study. Clin Nucl Med 2020;45(4):283-7. PMID 32108694
- 136
- Schrag A, Ben-Shlomo Y, Quinn NP. Prevalence of progressive supranuclear palsy and multiple system atrophy: a cross-sectional study. Lancet 1999;354:1771-5. PMID 10577638
- 137
- Schrag A, Selai C, Quinn N, et al. Measuring quality of life in PSP: the PSP-QoL. Neurology 2006;67:39-44. PMID 16832075
- 138
- Sharma P, Garg RK, Somvanshi DS, Malhotra HS. Progressive supranuclear palsy like syndrome: neurocysticercosis an unusual cause. Neurol India 2011;59:484-5. PMID 21743198
- 139
- Sharma M, Ioannidis JP, Aasly JO, et al. A multi-centre clinico-genetic analysis of the VPS35 gene in Parkinson disease indicates reduced penetrance for disease-associated variants. J Med Genet 2013;49(11):721-6. PMID 23125461
- 140
- Smith PY, Delay C, Girard J, et al. MicroRNA-132 loss is associated with tau exon 10 inclusion in progressive supranuclear palsy. Hum Mol Genet 2011;20(20):4016-24. PMID 21807765
- 141
- Smith R, Pawlik D, Nilsson CF, Englund E, Hansson O. [18F]Flortaucipir distinguishes Alzheimer's disease from progressive supranuclear palsy pathology in a mixed-pathology case. Acta Neuropathol 2020;139(2):411-3. PMID 31903496
- 142
- Smith R, Schöll M, Honer M, Nilsson CF, Englund E, Hansson O. Tau neuropathology correlates with FDG-PET, but not AV-1451-PET, in progressive supranuclear palsy. Acta Neuropathol 2017;133(1):149-51. PMID 27900460
- 143
- Sonies BC. Swallowing and speech disturbances. In: Litvan I, Agid Y, editors. Progressive supranuclear palsy: clinical and research approaches. New York: Oxford Univ Press, 1992.
- 144
- Stamelou M, de Silva R, Arias-Carrion O, et al. Rational therapeutic approaches to progressive supranuclear palsy. Brain 2010;133(Pt 6):1578-90. PMID 20472654
- 145
- Steele JC, Caparros-Lefebvre D, Lees AJ, Sacks OW. Progressive supranuclear palsy and its relation to pacific foci of the parkinson-dementia complex and Guadeloupean parkinsonism. Parkinsonism Relat Disord 2002;9(1):39-54. PMID 12217621
- 146
- Steele JC, Richardson JC, Olszewski J. Progressive supranuclear palsy: a heterogeneous degeneration involving the brain stem, basal ganglia and cerebellum, with vertical gaze and pseudobulbar palsy, nuchal dystonia and dementia. Arch Neurol 1964;10:333-59. PMID 14107684
- 147
- Swerdlow RH, Golbe LI, Parks JK, et al. Mitochondrial dysfunction in cybrid lines expressing mitochondrial genes from patients with progressive supranuclear palsy. J Neurochem 2000;75:1681-4. PMID 10987850
- 148
- Terao Y, Fukuda H, Shirota Y, et al. Deterioration of horizontal saccades in progressive supranuclear palsy. Clin Neurophysiol 2013;124(2):354-63. PMID 22883477
- 149
- Troost BT, Daroff RB. The ocular motor defects in progressive supranuclear palsy. Ann Neurol 1977;2:397-403. PMID 617579
- 150
- Tsai RM, Lobach I, Whitwell JL, et al. Clinical correlates and baseline predictors of progressive brain atrophy in progressive supranuclear palsy: results from the AL-108-231 davunetide trial (P5.006). Neurology 2015;84(14):Supplement P5.006.
- 151
- Valentino RR, Koga S, Heckman MG, et al. Association of tripartite motif containing 11 rs564309 with tau pathology in progressive supranuclear palsy. Mov Disord 2020;35(5):890-4. PMID 32142177
- 152
- Varanese S, Di Ruscio P, M’Barek L, Thomas A, Onofrj M. Responsiveness of dysphagia to acute L-Dopa challenge in progressive supranuclear palsy. J Neurol 2014;261(2):441-2. PMID 24413640
- 153
- Wagshal D, Sankaranarayanan S, Guss V, et al. Divergent CSF τ alterations in two common tauopathies: Alzheimer's disease and progressive supranuclear palsy. J Neurol Neurosurg Psychiatry 2015;86(3):244-50. PMID 24899730
- 154
- Wakabayashi K, Takahashi H. Pathological heterogeneity in progressive supranuclear palsy and corticobasal degeneration. Neuropathology 2004;24:79-86. PMID 15068177
- 155
- Walter U, Behnke S, Eyding J, et al. Transcranial brain parenchyma sonography in movement disorders: state of the art. Ultrasound Med Biol 2007;33:15-25. PMID 17189043
- 156
- Walter U, Dressler D, Wolters A, Probst T, Grossmann A, Benecke R. Sonographic discrimination of corticobasal degeneration vs progressive supranuclear palsy. Neurology 2004;63:504-9. PMID 15304582
- 157
- Warren NM, Piggott MA, Greally E, Lake M, Lees AJ, Burn DJ. Basal ganglia cholinergic and dopaminergic function in progressive supranuclear palsy. Mov Disord 2007;22(11):1594-600. PMID 17534953
- 158
- Whitwell JL, Avula R, Master A, et al. Disrupted thalamocortical connectivity in PSP: a resting-state fMRI, DTI, and VBM study. Parkinsonism Relat Disord 2011b;17(8):599-605. PMID 21665514
- 159
- Whitwell JL, Duffy JR, Strand EA, et al. Neuroimaging comparison of primary progressive apraxia of speech and progressive supranuclear palsy. Eur J Neurol 2013a:20(4):629-37. PMID 23078273
- 160
- Whitwell JL, Jack CR Jr, Parisi JE, et al. Midbrain atrophy is not a biomarker of progressive supranuclear palsy pathology. Eur J Neurol 2013b;20(10):1417-22. PMID 23078273
- 161
- Whitwell JL, Master AV, Avula R, et al. Clinical correlates of white matter tract degeneration in progressive supranuclear palsy. Arch Neurol 2011a;68(6):753-60. PMID 21670399
- 162
- Whitwell JL, Schwarz CG, Reid RI, Kantarci K, Jack CR Jr, Josephs KA. Diffusion tensor imaging comparison of progressive supranuclear palsy and corticobasal syndromes. Parkinsonism Relat Disord 2014;20(5):493-8. PMID 24656943
- 163
- Williams DR, de Silva R, Paviour DC, et al. Characteristics of two distinct clinical phenotypes in pathologically proven progressive supranuclear palsy: Richardson's syndrome and PSP-parkinsonism. Brain 2005;128(Pt 6):1247-58. PMID 15788542
- 164
- Williams DR, Holton JL, Strand C, et al. Pathological tau burden and distribution distinguishes progressive supranuclear palsy-parkinsonism from Richardson's syndrome. Brain 2007a;130:1566-76. PMID 17525140
- 165
- Williams DR, Lees AJ. Progressive supranuclear palsy: clinicopathological concepts and diagnostic challenges. Lancet Neurol 2009;8:270-9. PMID 19233037
- 166
- Williams DR, Pittman AM, Revesz T, Lees AJ, de Silva R. Genetic variation at the tau locus and clinical syndromes associated with progressive supranuclear palsy. Move Disord 2007b;22:895-7. PMID 17274033
- 167
- Winikates J, Jankovic J. Vascular progressive supranuclear palsy. J Neural Transm Suppl 1994;42:189-201. PMID 7964687
- 168
- Zangini S, Calandra-Buonaura G, Manners DN, et al. Accuracy of MR markers for differentiating Progressive Supranuclear Palsy from Parkinson's disease. Neuroimage Clin 2016;11:736-42. PMID 27330973
- 169
- Zarei M, Poretemad HR, Bak T, Hodges JR. Autbiographical memory in progressive supranuclear palsy. Eur J Neurol 2010;17:238-41. PMID 19780809
- 170
- Zhao Y, Tseng IC, Heyser C, et al. Appoptosin-mediated caspase cleavage of tau contributes to progressive supranuclear palsy pathogenesis. Neuron 2015;87(5):963-975. PMID 26335643
- 171
- Zwergal A, Schoberl F, Mohwald K, Hoglinger G, Brandt T, Dieterich M. P22. Long-term course of progression of clinical ocular motor signs in progressive supranuclear palsy. Clin Neurophysiol 2018;129(8):e76. Accessed online via https://doi.org/10.1016/j.clinph.2018.04.664.
Contributors
All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.
Author
-
Robert Fekete MD
Dr. Fekete of New York Medical College received consultation fees from Acadia Pharmaceutical, Acorda, Adamas/Supernus Pharmaceuticals, Amneal/Impax, Kyowa Kirin, Lundbeck Inc., Neurocrine Inc., and Teva Pharmaceutical, Inc.
See Profile
Former Authors
- Lawrence I Golbe MD
Patient Profile
- Age range of presentation
-
- 19 years to 65+ years
- Sex preponderance
-
- male>female, >1:1
- Heredity
-
- A link to the H1 haplotype of the tau gene on chromosome 17 has been confirmed in progressive supranuclear palsy but accounts for only a portion of its etiology.
- Population groups selectively affected
-
- none
- Occupation groups selectively affected
-
- none
ICD & OMIM codes
- ICD-10
-
- Progressive supranuclear palsy: G23.1
- OMIM
-
- Progressive supranuclear palsy 1: #601104
- Progressive supranuclear palsy 2: %609454
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