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Atypical Parkinsonism

What is Drug-Induced Parkinsonism?

  • Parkinsonism is defined as stiffness (rigidity), slowness (bradykinesia) and occasionally tremor (usually resting tremor.)  Many things can cause parkinsonism (not just Parkinson disease).  Medications that interfere with or block dopamine can lead to a clinical picture that looks like Parkinson Disease but in reality is much different in prognosis and treatment.

  • Medications that can block dopamine and lead to parkinsonism include (in no particular order): 

    • valproic acid​ (Depakote)

    • metaclopramide (Reglan)

    • anti-psychotics (risperidol, haldol, olanzapine, ziprasadone, chlorpromazine)

    • tetrabenazine

    • some anti-depressants such as aripiprazole (Abilify)

    • some anti-arrhythmic agents like amiodorone

  • stiffness and slowness​ is usually symmetric but someones can be on only one side making it hard to distinguish from Parkinson Disease

  • The diagnosis is made based on history and sometimes by obtaining a DAT (dopamine transporter) scan which is normal in the case of drug-induced parkinsonism.

  • Treatment includes removing the offending agent keeping in mind it may take weeks or months for symptoms to improve.  

What is Progressive Supranuclear Palsy (PSP)?

  • PSP is a cousin of Parkinson Disease that is caused by a different protein (Tau protein.)  This protein is similar to the abnormal protein in Fronto-temporal Dementia (FTD) and corticobasal degeneration (CBD).  

  • PSP is marked by early gait and balance difficulty with early falls and postural instability (loss of the reflex to catch oneself when falling.)  Neck and trunk rigidity is also common much more so than stiffness in arms or legs.  

  • There is also more of rapid progression than regular Parkinson Disease

  • Patients often complain of double vision (diplopia) as the abnormal protein will often affect the eye movements in the vertical (up and down) plane.  

  • The voice is monotonous at times and swallowing can be impaired (dysphagia)

  • The diagnosis is made on the physical exam and by obtaining an MRI looking for shrinking (atrophy) of the midbrain.  

  • carbidopa/levodopa is often given but usually of only modest benefit.  Other treatments are supportive and include medications for memory and cognition, botulinum toxin injections for the involuntary closing of the eyes (apraxia of eyelid opening) and for pain and stiffness in the neck region.  Medication is often given for the involuntary crying or laughing (pseudobulbar affect or PBA.)  

  • Newer treatments are underway.

What is Multiple System Atrophy (MSA)?

  • MSA is caused by the same abnormal protein as in Parkinson Disease (alpha-synuclein)  

  • Patients can have parkinsonism (stiffness and slowness) but also tend to have a jerky and mixed tremor (both resting and action tremor)

  • There is another subtype (called the cerebellar subtype) that is characterized by lack of coordination in the arms and walking (ataxia)

  • One of the major hallmarks of MSA is the dysfunction of the autonomic nervous system.  This includes symtpoms such as:​​

    • neurogenic orthostatic hypotension (NOH) - drop in blood pressure beyond what the brain can handle leading to dizziness and sometimes passing out (syncope)​

    • constipation

    • urinary urgency

    • getting full early (early satiety)

    • lack of sweating

    • dry mouth and dry eyes

  • The diagnosis is made by the physical exam, history, and sometimes is supported by certain findings on an MRI.​

  • Treatment is usually aimed at treating the symptoms although carbidopa/levodopa is still often tried but usually has only a modest benefit.

  • This condition tends to progress more rapidly than Parkinson Disease​

What is Corticobasal Degeneration (CBD)?

  • CBD is caused by the same protein (Tau) involved with fronto-temporal dementia (FTD) and progressive supranuclear palsy (PSP)

  • Signs on exam include asymmetrical parkinsonism (stiffness and slowness), jerky tremor at rest and with action, twitching (myoclonus), abnormal posturing usually of the hand (dystonia), and alien-limb syndrome (floating of the arm or leg with a "mind of its own."

  • Also early on, there is cognitive decline with difficulty with judgement, planning, and apraxia (forgetting once-learned movements and subjects).  

  • Treatment is often supportive and may include botulinum toxin, medications for cognitive decline and may even include carbidopa/levodop (although the benefit is usually only modest.)  

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