Movement disorders

• upper motor neuron --pyramidal--cell bodies in cortex
• lower motor neuron--cell bodies in brain stem (face, eyes) / spinal (arms and legs) project out to muscles muscle--part of NS
• extrapyramidal (basal ganglia)--affect basal ganglia
• cerebellar--also part of motor system

a lesion anywhere along upper motor neuron pathway produces same clinical symptoms/syndrome

upper motor= homunculous, surface of cortex

• UPN lesions cause:
• - weakness in the extensors of the upperlimbs and flexors of lower limbs,
• - spasticty--increase in muscle, tells you where lesion is, not cause
• - increased stretch reflex
• - Babinski sign--flexors (toes) usually go down when sole of tood is stroked, in UMN lesion, toes go up

• - resting tremor in hands, feet and jaw, tremor goes away when using the part
• - can be asymetric, most often
• - short shuffling steps, gait changes with visual input e.g. if he has to step over lines

Treatments--> levodopa, can't just give dopamine, doesn't cross BBB, levodopa can cross and then is converted into dopamine

neuronal loss in the substatia nigra--projects from midbrain to striatum, loss of these neurons= decreased dopamine

nigrostriatal projects

• neurotransmitter= dopamine
• - tyrosine converted to DOPA converted dopamine, released at the nerve ending in the substantia nigra. - This part is deficient in Parkinsons

- unknown

environmental influences--in silacon valley, IV drug users exposed to MPTP, selectively toxic to domapinergic neurons, development all the features of Parkinsons--led to the animal model

genetic influences -- most likely due to a genetic suceptibility and environment exposure

• - weakness- in a specific peripheral nerve/muscle
• - reduced muscle bulk--in specific areas
• - fasciculations--muscle twitches
• - reduced stretche reflexes in muscle affected

• BG--cautade nucleus + putamen= striatum
• putamen + gobus pallidum = lentiform

• hypokinetic (too little movement, decreased voluntary movement)
• - syndromes characterized by impoverished voluntary movement

• hyperkinetic (too much movement, increased involuntary movement)
• - syndromes characterized by abnormal involuntary movements

• bradykinesia
• akinesia
• rigidity
• “akinetic‐rigid syndromes”
• “parkinsonism”

• rest tremor
• bradykinesia
• rigidity
• postural instability

• can occur in :
• Parkinson’s disease
• drug induced parkinsonism --> dopamine‐blocking drugs
• other neurodegenerative syndromes
• - progressive supranuclear palsy
• - multiple system atrophy
• - Lewy body disease

in early disease, sustain motor response even though concentration of levadop in the blood decreases after a while after taking it.

after a period of time on the drugs, the effect wears off as the dose deteriorates, causes diskinesias, abmornal twitches, not rhythmic, flowing movements between body parts, usually at the peak of the drug dose

increased activity that is responsible for clinical abnormalities, in the STN

correcting activity in STN or GP can correct problems

lesions--surgical lesions in GP, decreases PD features on the opposite side, right by the internal capsule which contains the corticospinal pathways, and if these are affected you can get a UMP lesion which is irreversible

stimulatin the structure has the same effect as a lesion, STN electordes emplanted while awake.

• involuntary, rhythmic, sinusoidal
• classified by :
• - relation to activity : rest, postural (only in certain positions), kinetic (during voluntary movements)

• etiology-->
• physiological (everyone has it, accentuated in certain situations like stress)
• essential (common, postural/kinetic tremor, aggravated by stress, anxiety etc, alcohol responsive),
• - significant functional disability, difficult to treat but can be by stimulating electrodes in thalamus
• parkinsonian
• cerebellar

irregular, unpredictable, purposeless, rapid movements that flow randomly from one body part to another

e.g. Huntingtons

• inherited neurodegenerative disorder
• - autosomal dominant
• - 100% penetrance
• - age of onset: 35 ‐ 45 yr

• motor, cognitive, and behavioural dysfunction
• - inexorably progressive
• - death 15 ‐ 20 yr after symptom onset

• motor dysfunction (usually comes first)
• - chorea is usually the earliest sign : initially fingers, toes, face, progressive
• - dystonia and parkinsonian features later
• - progressive incoordination, unsteadiness, immobility, dysarthria, dysphagia

• cognitive impairment
• - some degree is inevitable but occasionally minimal

• behavioural disorders
• - gradual change in personality --> reported by family
• - affective disorders in 30‐40%
• - schizophrenia and other psychoses in 10%
• - high suicide risk

• pathology
• - striatal atrophy
• - neuronal loss and gliosis
• - most striking in, but not limited to striatum
• - diffuse cortical changes, primarily frontal
• - degree of pathology is related to the duration of symptomatic HD

• autosomal dominant
• chromosome 4
• very low spontaneous mutation rate

everyone has the gene (human IT15 gene), but normally have less of it

• huntingtin--protein needed for brain development, plays a critical role in neurogenesis
• in a transgenic mous, reduced levels of huntingtin associated with aberrant brain development and perinatal lethality

no known treatment effective at altering progression, can treat symptoms

• large amplitude, violent, flinging movements in proximal muscle groups, typically unilateral
• - hemiballismus --> subthalamic nucleus stroke

• sustained muscle contraction, often giving rise to twisting, repetitive movements, or to sustained postures
• - idiopathic (genetic ?)
• - inherited disorders of metabolism
• - focal basal ganglia lesions

• dystonia--meige syndrome--> frequent eyeblinks, forced eyelid closure, involuntary facial movements
• --normal brain, abnormality in function not structure

dystonia--task specific--sustained rasing of middle finger, affects actions important to person

dystonia--generalized-- genetic from DYT1 mutation, sustained muscle contraction but intellecturally fine

• Hemispheral lesions
• - limb ataxia, intention tremor, hypotonia (low muscle tone)

Vermal lesions--gait ataxia