Atypical Parkinsonism

Question 1

PSP

Answer 1

Pathology: atrophy of midbrain, subthalamic nucleus, dentate nucleus, SCP, frontal cortex

• symmetric akinetic rigid syndrome
• lack of resting tremor
• no response to levodopa
• axial rigidity
• supranuclear gaze palsy, typically limited downgaze
• reduced vertical optokinetic nystagmus
• diplopia, blurred vision
• reduction in blink rate and lid retraction–> staring appearance
• square wave jerks–> involuntary horizontal saccades that go to right, then to left with brief pauses before changing direction
• loss of postural reflexes–> falls
• dementia–> frontal-subcortical, classic PSP, bradyphrenia (difficulty shifting tasks and paying attention, subcortical dementia); other PSP subtypes, dementia may differ;
• furrowed brow (angry or puzzled look)
• hypophonia
• dysphagia early in course of the disease
• gunslinger gait
• gait freezing
• blephrospasm
• apraxia of eyelid opening (unable to open eyes, even after inactivation of orbitcularis oculi)
• frontal release signs: glabellar, snout, and grasp
• pseudobulbar palsy (emotional incontinence)

***supranuclear gaze palsy, early loss of postural stability, growling voice, furrowed brow, apraxia of eyelid opening, early dysphagia…clues to diagnosis

MRI: hummingbird/mickey mouse sign

Question 2

Corticobasal degeneration

Answer 2

Probable CBS
1.)asymmetric presentation of 2 of the following:

• limb rigidity of akinesia
• limb dystonia
• limb myoclonus

PLUS 2 of the following:

• apraxia (orobuccal/limb)
• cortical sensory deficit
• alien limb phenomenon

Other signs as well…

• no tremor
• loss of balance occurs earlier
• does not respond to dopamine replacement therapy

Cortical signs:

• hesitant and dysarthric speech
• aphasia and apraxia of speech
• apraxia
• cortical sensory loss–> 2 point discrimination, agraphesthesia, astereognosis
• cortical myoclonus
• alien limb phenomenon
• hemiparesis
• **summary, cortical deficits are myoclonus, apraxia, and aphasia

Pathology: asymmetric cortical atrophy (frontoparietal)

• vaculoated neurons in atrophic cortical areas
• ballooned neurons contain phosphorylated neurofilaments and sometimes tau and ubiquitin
• neuronal loss and gliosis in GP, putamen, red nucleus, thalamus, subthalamic nucleus, SN, locus coeruleus, dentate nucleus

Treatment: supportive

1. ) myoclonus: clonazepam, keppra
2. ) rigidity/dystonia: botox

Question 3

MSA

Answer 3

Pathology: misfolded alpha-synuclein

• atrophy in striatonigral, cerebellar, autonomic, and cortiospinal pathways
• involve the SN, GP, cerebellum, MCP, inferior olives, intermediolateral cell columns, corticospinal tracts, anterior horn cels, etc.
• central preganglionic sympathetic neurons are affected (plasma epinephrine is normal when patient in supine, fails to rise when patient stands)….differentiates from Lewy body disease (autonomic impairment affects peripheral postganglionic neurons)

Middle-aged patients

• Parkinsonism (MSA-P, bradykinesia and rigidity, no resting tremor, symmetric)
• autonomic insufficiency
• cerebellar abnormalities (MSA-C)

Other symptoms:

• axial dystonia (anterocollis)
• stridor
• REM behavior
• dementia: frontotemporal lobar degeneration-synuclein

Risk of anoxic damage from stridor and cardiopulmonary arrest due to autonomic dysfunction

DDx: PSP, CBD, Spinocerebellar ataxias (type 1,2,3,6,7), fragile X tremor-ataxia syndrome,

MRI: putaminal slit sign (hyperintensity in the putamen), hot cross bun sign (cruciform increased signal in pons)