Extrapyramidal Motor System

      Descending extrapyramidal paths receive input from other parts of motor system:

    From the cerebellum

    From the basal ganglia or “corpus striatum”


Basal Ganglia or “Striatum”

      Caudate & putamen get input from cortex, thalamus & substantia nigra, a midbrain motor area

      They send commands to globus pallidus which sends them on to the motor portions of thalamus & brainstem

      Very interconnected system with lots of feedback loops


Basal Ganglia or Striatum

      Interconnected set of nuclei (gray matter) buried within the cerebral hemispheres that have primarily motor functions

      Best known components:

    Caudate nuclei (“tail shaped nuclei”)

    Putamen (“seashell”)

    Globus pallidus (“pale globe”)


      The basal ganglia are important for:

    Initiating or starting motor programs   often multiple programs at once

    Inhibiting undesired movements; terminating voluntary movements




Parkinson’s Disease
(paralysis agitans or shaking palsy)

      About 1% of those over 50 have PD (~ 1,000,000 total in US; 55,000 new cases/yr; 90% cases occur after age 60)

      Progressive deterioration of major DA input to basal ganglia- the “nigrostriatal pathway” from substantia nigra to the “striatum”

      We lose about 4% of those DA neurons/decade, but those with PD have accelerated loss (70% or more gone)

      Results in difficulty initiating movements & tremor


      The nigrostriatal path sends DA messages from the substantia nigra to the basal ganglia.

Classic PD Symptoms

      Worsening bradykinesia & akinesia

      Rigidity; clumsiness, decreased postural stability so tends to fall

      “Pill-rolling” tremor-at-rest

      Reduction in movement is also seen in lack of facial expression & blinking; shuffling walk without assoc. arm movements; soft, halting, monotone voice; slow blinks; small writing; feeling stuck or frozen

Possible Causes

      Environmental toxin of some sort (industrial heavy metals, pesticides, “free radicals” currently under study)

      Genetics (especially in those who get PD at an early age)

      Brain trauma may increase your risk


      Increase DA production with l-dopa/carbidopa (Sinemet)

      Problems: l-dopa induced dyskinesias and loss of effectiveness over time

      Others: DA agonist (bromocriptine/Parlodel or pergolide/Permax, or newer, better Mirapex, Requip) or DA releasor (amantadine/Symmetrel)

      Eldepryl/Deprenyl (selegiline) to decrease DA breakdown and slow loss of neurons

      Anti-ACh drugs (Artane, Cogentin) can help restore chemical “balance” of basal ganglia


When Drug Therapy Fails

      When drug effectiveness declines, exp. options include:

    Pallidotomy; thalamotomy (Michael J. Fox)

    Deep brain (thalamic) stimulation

    Transplant of DA producing cells



Parkinson’s Disease Update

      Although PD is thought of as a motor disorder, the decline in DA also produces cognitive and emotional changes in some

     bradyphrenia” (cognitive slowing); decreased attention

     frontal lobe” symptoms (disinhibition of behavior, poor judgment and planning)

     Major depression

     Full-blown dementia in ~50% (associated with neuropathological sign called Lewy bodies)

     PD treatment, on the other hand, can produce hallucinations and other symptoms of psychosis

Impairment of the Inhibitory Functions of the BG

      Dyskinesias – involuntary movements

    Chorea (“dance-like”) – quicker irregular movements

    Athetosis – slower writhing, twisting movements

      Dystonias – abnormalities of excessive muscle tone

Huntington’s Disease

      Transmitted by a dominant gene on chromosome 4 (about 30,000 US cases with 150,000 at risk kids)

      Deterioration of striatum produces involuntary chorea, athetosis & other motor difficulties

      Cortical deterioration causes progressive & debilitating dementia, aggressiveness, mood swings, depression, psychosis

      Death due to health complications in 15-20 yrs

Huntington’s Disease

      Bad gene has excess “CAG repeats” (more than 36-250 instead of usual 29 or fewer) resulting in an abnormal form of protein known as huntingtin.

      The more repeats, the earlier symptoms appear.

      # of repeats can increase across generations, especially in kids inheriting gene from father

      Brain damage may be due to decrease in normal protective huntingtin + adverse effects of abnormal protein on critical growth factors keeping cells alive.

      Also looking at effects on excitotoxins & glucose metabolism.

Treatments for HD

      Genetic testing  to identify presence of the gene

      Involuntary movements may be decreased by DA blockers (antipsychotics)

      New drugs being tried to delay progression:

     Rilutek (riluzole), Neurontin (gabapentin) decrease glutamate transmission

     Rapamycin (transplant drug) speeds elimination of abnormal protein

     Growth factor supplementation being studied

      Experimentation with brain cell transplants/surgeries is underway

Tourette Syndrome

      Another *hereditary BG disorder characterized by involuntary movements

      Multiple motor tics - simple tics of face or limbs and/or more organized complex tics (touching, grimacing, pinching, poking, adjusting, hitting, jumping, kissing, throwing, gestures) plus:

      Phonic or vocal tics - both simple (throat-clearing, coughing, hiccuping, grunting, yelping) and/or complex tics (actual words, coprolalia, echolalia, palilalia, assuming different voices, talking to oneself in different voices)

      Seems to affect frontal lobe- BG connection that is important for our ability to inhibit actions

Tourette Syndrome

      40% report “sensory tics” – uncomfortable  sensations that may be a reason for some of the involuntary movements

      Some degree of suppressibility, but individual experiences increased tension until tic is released

      Pattern of tics changes & waxes & wanes with changes in stress, anxiety, fatigue.

      Treated with DA blockers (antipsychotics). Milder tics may respond to NE agonist clonidine.

      Majority experience decreased tics as adults.

Link with Other Disorders

      ~50-60% also suffer OCD (others estimate that up to 90% experience some involuntary touching compulsions, ritualistic behaviors, intrusive thoughts)

      ~50-90% show evidence of ADHD as well; first signs of GTS are usually impulsive, hyperactive behaviors (before tics appear)

      About 30% have learning disabilities, emotional lability, rage, aggressiveness; 40-50% depressed

      Evidence suggests a single gene with sex-linked, varied forms of expression of disinhibition

      50-73% concordance in identical twins vs 8-22% in fraternal twins