Table 1.
Chameleons of PSP and CBS.
| Disease entity | Phenotypic presentations (Chameleons) | Clinical clues |
|---|---|---|
| Progressive supranuclear palsy (PSP) (13, 16, 25) | PSP-Richardson's syndrome (PSP-RS) | Vertical supranuclear gaze palsy (VSGP), slowing of vertical saccades, early postural instability within 3 years, axial rigidity, retrocollis, hyperactivity of frontalis and procerus muscle (“Reptilian stare,” “Procerus sign”) |
| PSP-parkinsonism (PSP-P) | Initially mimics Parkinson's disease (PD), prominent axial symptoms, attenuated response to levodopa, along with VSGP or slow vertical saccade, hypokinesia without decrement, micrographia without decrement in script size (26), freezing of swallowing (27) are helpful clinical clues | |
| PSP-Progressive gait freezing (PSP-PGF) | Gait ignition failure, start hesitation, progressive freezing of gait (FOG) within 3 years, along with VSGP or slow vertical saccade, stuttering or stammering speech, axial rigidity without appendicular rigidity, fast micrographia, rapid hypophonia, or tachyphemia | |
| PSP-Corticobasal syndrome (PSP-CBS) | VSGP/slow vertical saccade with features of CBS like delayed initiation of horizontal saccade, limb apraxia, dystonia, myoclonus, cortical sensory loss | |
| PSP-speech/language disorder (PSP-SL) or PSP-PNFA | VSGP or slow vertical saccade with features of PNFA like progressive apraxia of speech (AOS), agrammatism, phonemic errors | |
| PSP-frontal variant (PSP-F) | VSGP/slow vertical saccade with frontal cognitive/behavioral presentation like apathy, dysexecutive syndrome, reduced phonemic verbal fluency, impulsivity, disinhibition, perseveration | |
| PSP-postural instability (PSP-PI) | Isolated postural instability within 3 years (repeated unprovoked falls or fall during pull test) | |
| PSP-ocular motor (PSP-OM) | Isolated VSGP/slow vertical saccade/macro square wave jerk or eyelid opening apraxia | |
| PSP-primary lateral sclerosis (PSP-PLS) (28) | PSP phenotype with marked upper motor neuron (UMN) signs (may be a clinical clue for underlying GGT pathology) | |
| PSP-cerebellar ataxia (PSP-C) (29) | Progressive truncal and limb ataxia | |
| Can mimic multisystem atrophy (MSA-C) or idiopathic late onset cerebellar ataxia (ILOA); early falls, VSGP, no dysautonomia, cognitive dysfunction are helpful clinical clues for PSP-C | ||
| Corticobasal syndrome (CBS) | Classic CBS phenotype (CBD-CBS) (30) | Asymmetric parkinsonism, limb dystonia, myoclonus, saccadic apraxia, ideomotor apraxia, cortical sensory deficits, alien limb phenomena |
| Non fluent/agrammatic variant Primary progressive aphasia phenotype (CBD-PNFA) (30) | Apraxia of speech (AOS), agrammatism | |
| Frontal behavioral-spatial syndrome (FBS/ CBD-bvFTD) (30) | Executive dysfunction, disinhibited behavior, personality changes | |
| Mimics bvFTD, but with additional visuospatial and visuoconstructive deficits | ||
| PSP-RS-like phenotype (PSPS/CBD-RS/CBD-PSP) (30) | VSGP or slowing of vertical saccade, axial rigidity, postural instability, early falls | |
| Amnestic phenotype (31) | Mimics AD like dementia at onset, additional asymmetric motor/sensory signs, hyperreflexia, gait impairment, parkinsonism, dystonia are clinical clues | |
| Posterior variants clinically presenting with Posterior cortical atrophy (CBD-PCA), Gerstmann-variant or Balint syndrome (32) | Symmetric bi-parietal syndromic presentation with asymmetric progression, progressive visuospatial impairments, fluent aphasia, posterior alien hand, apraxia, agraphia, acalculia, optic ataxia, oculomotor apraxia, simultagnosia with parkinsonism, myoclonus | |
| Progressive dysarthria and orofacial apraxia variant (33) | Presents with progressive loss of speech output, orofacial apraxia (OFA) for lower facial and tongue movements, later development of myoclonus, limb apraxia, akinetic-rigid parkinsonism | |
| Prominent pseudobulbar effect and dysarthria, emotional lability variant (34) | Presents with spastic dysarthria, pathological laughter/crying, later development of asymmetric rigidity, dystonic posturing | |
| Progressive conduction aphasia (35) | Presents with progressive language problem with preserved fluency and comprehension but with paraphasia and marked impairment in repetitions of words or phrases | |
| Frontal-type gait impairment (36) | Presents with difficulty to initiate gait, imbalance during walking, marked anxiety for falling, upper limb dyspraxia, paratonia, frontal release signs |