Extra Pyramidal Side Effects

8/7/2019 Extra Pyramidal Side Effects

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Neurologic syndromes in which abnormalmovement occur due to a disturbance offluency and speed of voluntary movement or

the presence of unintended extra movements


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Results from dysfunction of the extrapyramidalsystem

Basal ganglioncaudate, putamen, globus

pallidus, subthalamic nucleus, and substantianigra

motor area of cortex--> basalgangalion(organizing movement commands) -->

motor area of cortex# affects the size and speed of movements

# selection of components of movements or the sequencingof multi-step movements


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Direct pathway

Dopamine D1 type medium spiny neuron internal portion of globuspallidus ventral anterior/ventral lateral region of thalamus c

ortexIndirect pathway

Dopamine D2 type medium spiny neuron external portion of globuspallidus subthalamic nucleus internal portion of globus pallidus

ventral anterior/ventral lateral region of thalamus cortex


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EPS secondary to pharmacologic agents are themost common.

The risk of developing a drug-induced EPS begins

at the onset of treatment with an offending agent. Acutely: within hours or a few days

Subacutely: over several weeks

Late or delayed onset: six months or longer afterexposure(tardive)

short-term therapy of minimal therapeutic dosagesshould be the strategy employed


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Five classes of drugs are known to affect centraldopaminergic systems

Central stimulantsact as indirect dopamine agonist ex.

Amphetamine Levodopaa precursor of dopamine

Direct dopamine agonistex. Bromocriptine

Presynaptic dopamine antagonists ex. Reserpine

Antagonize or block central dopamine receptors

neuroleptics, metoclopramideprimperam


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Acute dystonia

Parkinsonism

Akathisia

Tardive dyskinesia


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Dystonia (from Greek, meaning altered muscletone) refers to a syndrome of involuntarysustained or spasmodic muscle contractions

involving co-contraction of the agonist and theantagonist. The movements are usually slowand sustained, and they often occur in arepetitive and patterned manner; however,

they can be unpredictable and fluctuate. Thefrequent abnormal posturing and twisting canbe painful and functionally disabling.


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focal dystonia

30 per 100,000

generalized dystonia

3 per 100,000

5 10 times greater in Ashkenazi Jewish


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1. Primary dystonia

no structural abnormality in the CNS(oftengenetic)

Childhood onset idiopathic torsion dystonia(DYT-1)

Adult onset idiopathic dystonia (focal,

segmental)


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Secondary (Acquired)

structural lesion (basal ganglia putamen, globus

pallidus, subthalamic nucleus or thalamus)

S

troke, tumor, AVM, injury perinatal hypoxia (associated with cerebral palsy)

CNS infections, inflammatory disorders

toxins cyanide (P), carbon monoxide, methylalcohol(GP)

drug induced (tardive dystonia) neuroleptics,

antiemetics, antiepileptics

acute dystonia reaction - neuroleptics


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Drug-induced supersensitivity of striataldopamine receptors or abnormality of gammaaminobutyric acid (GABA) ergic neurons are

proposed mechanisms for some drug-induceddystonias.


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Symptoms vary according to the kind ofdystonia involved. In most cases, dystoniatends to lead to abnormal posturing,

particularly on movement. Many sufferershave continuous pain, cramping and relentlessmuscle spasms due to involuntary musclemovements. Other motor symptoms are

possible including lip smacking.[


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Parkinson's disease

essential tremor

carpal tunnel syndrome

TMD

Tourette's syndrome or other neuromuscularmovement disorders.


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Electrical sensors (EMG) inserted into affectedmuscle groups, while painful, can provide adefinitive diagnosis by showing pulsating

nerve signals being transmitted to the muscleseven when they are at rest.


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The functional impact of dystonia varies from barelynoticeable to severely disabling. Dystonias can have aprofound effect on a patient's personal, vocational, andemotional life and can impact his/her ability to liveindependently. Psychologic counseling and participation in

support groups are vital adjuncts to medical and physicalapproaches in the multidisciplinary management ofdystonia.

The options to medically manage dystonic movements havetraditionally been 4-fold; they consist of the following:

Rehabilitative therapies Oral medications Neurochemolytic interventions Surgery


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As with most movement disorders, dystonia maybe influenced by fatigue, anxiety, relaxation, orsleep. Thus, attention to overall health,environment, and stressors can make dystoniamore manageable.[10, 11]

Dystonic movements are often exacerbated ortriggered by voluntary or intentional movementsof the same or other body parts. Involuntary

movements can be transiently suppressed by acontact stimulus, such as placing a hand on theipsilateral or contralateral side of the face or neckof a patient with spasmodic torticollis.


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Physical therapy techniques (eg, massage),slow stretching, and physical modalities (eg,ultrasonography, biofeedback) are sometimes

helpful in persons with focal or regionaldystonias. Patients with generalized dystoniaoften benefit from gait and mobility training, aswell as from instruction in the use of assistive

devices.


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Successful drug therapy often requirescombinations of several medications, withchoices generally guided by empirical trials

and adverse effect profiles.Doses should beslowly increased over the course of weeks ormonths until the therapeutic benefit isoptimized or until adverse effects occur. In

most patients, discontinuation of the drugsrequires tapering to prevent withdrawalsymptoms.


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Baclofen, given intrathecally by an implantedpump, can be very effective in certain types ofdystonia, especially if spasticity co-exists.[9]Due

to the low prevalence of side effects when themedicine is delivered into the cerebrospinalfluid, the ability to deliver the medicinecontinuously, and the ability to test the

therapeutic effect prior to proceeding withsurgery, this option may provide effectivetreatment for many patients.


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Neurochemolysis of dystonic muscles isanother important therapeutic option.Botulinum toxins or phenol/alcohol injections

have become powerful tools in improving thesymptomatic treatment of focaldystonias.These injections temporarily reducethe ability of the muscles to contract and may

be the treatment of choice for blepharospasm,cervical dystonia, and hemifacial spasm.


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Botulinum toxins are produced by the gram-negative bacterium Clostridium botulinum andact by inhibiting the presynaptic release of

acetylcholine at the neuromuscular junction. Ofthe 7 immunologically distinct botulinum toxinserotypes, only types A and B are approved forclinical use. Onset of effect takes several days

after injection.


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Surgical options for intractable dystoniasinclude altering the location or length ofproblematic muscles, but this is rarely

successful. Other techniques includetransection of the spinal accessory nerve forcervical dystonia, stereotactic thalamotomy orpallidotomy for generalized dystonia, and deep

brain stimulation (DBS)


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Thorough neurologic, physiatric,neuropsychologic, and physical therapyevaluations are important prior to

consideration for surgery. Because of the risk of significant comorbidity,

these approaches are reserved for patients withdisabling dystonia in whom other treatment

modalities have been exhausted.

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Extra Pyramidal Side Effects