Dr.Demet Demircioğlu

The term extrapyramidal system, coined by British neurologist Kinnier Wilson, refers to the basal ganglia and an array of brain stem nuclei (red nucleus, reticular formation etc.) to which they are connected.

Components of the extrapyramidal system include the red nuclei, vestibular nuclei, superior colliculus and reticular formation in the brain stem, all of which project via discrete pathways to influence spinal cord motor neurons. Cerebellar projections are also included since they influence not only these brainstem motor pathways, but also the motor cortex itself via the dentatothalamic projection.

Basal gangliaSubcortical nucleiCaudate,

putamen & globus pallidus: corpus straitum

Caudate & putamen : straitum

Globus pallidus & putamen : lentiform nuclei

Globus pallidus :pallidum

Perhaps the most important structures to retain an extrapyramidal definition are the basal ganglia, Subcortical cell stations for the extra pyramidal motor pathway

The neostriatum (caudate and putamen) receives widespread cortical afferents, including those from high order sensory association and motor areas, and projects mainly to the globus pallidus. The latter nucleus is the major outflow for the basal ganglia and, via the ventral anterior thalamus, exerts its major influence on premotor and hence the motor cortices.

This pattern of connections suggests that the basal ganglia are involved in complex aspects of motor control, including motor planning and the initiation of movement.

pyramidal system extrapyramidal system

function Skilful volitional

movements

Modulate volitional motor

movements

Finalizes an act Initiate an act

connection Direct linkage to

spinal cord

Multi neuronal and multi

synaptic via descending tracts

Cortico bulbar and

cortical spinal tract

reticulo-spinal, rubro-spinal,

olivo-spinal and vestibulo-spinal

tract.

Clinical features spasticity Rigidity( lead pipe/ cog wheel)

Reflexes brisk normal

Power diminished Usually not affected

Planters extensor flexor

Involuntary movements absent present

Phylogenetically, corpus striatum is primarilyresponsible for stereotyped motor activities tomaintain tone, posture, locomotion and automaticassociated movement.

Regulation of voluntary motor activity

Control of the muscle tone

Maintenance of emotional and associative movements

It is now clear that in many extrapyramidal disorders there are specific changes in neurotransmitter profile rather than discrete anatomical lesions

1. Disturbance in the control of voluntary motor activity resultingin involuntary movements which may be of two main types:

Rhythmic and regular as in parkinsonism Dysrhythmic and irregular as in chorea, athetosis and dystonia2. Disturbance in the normal muscle tone resulting in hypertonia

(rigidity)3. Disturbance in the maintenance of emotional and associated

movements resulting in bradykinesia (mask face, infrequentblinking and loss of swinging during walking)

Extrapyramidal disorders are classified

broadly on clinical grounds into:

1. The akinetic-rigid syndromes in which

poverty of movements predominates

2. The dyskinesisas in which there are a

variety of excessive involuntary

movements

Akinetic-rigid syndromes

Idiopathic Parkinson's disease

Drug-induced parkinsonism (e.g. phenothiazines)

MPTP-induced parkinsonism [methylphenyltetrahydropyridine]

Postencephalitic parkinsonism

Parkinsonism-plus

Childhood akinetic-rigid syndrome

Dyskinesias

Essential tremor

Chorea

Hemiballismus

Myoclonus

Tic or 'habit spasms'

Torsion dystonias

Paroxysmal dyskinesias

Rhythmical

Tremor

Irregular

Slow or sustained

(Athetosis / dystonia)Rapid

Controllable

(Tics)Uncontrollable

Distal

(Chorea)

Proximal

(Ballismus)

Multifocal

(Myoclonus)

Only Cogwheel

rigidity or rest

tremor

(Parkinsonism)

Cognitive, language,

upper motor neuron

or sensory sign

(Degenerative

disease with

parkinsonism)

Age- age of disease onset is very important tourettesyndrome, typically begins in the first decade, parkinsons disease usually occurs in late age

Past history –About infection (rheumatic fever), jaundice(wilsons disease) • Medical history & Toxin exposure

Drug history- of current, previous & recreational use should be taken details : parkinsonism & dystoniamay be produced by dopamine receptor blocking agent

Family history – should be taken and make a pedigree chart if necessary (huntington disease)

Associated neuropsychiatric features –Wilson disease, Huntington disease

Autonomic symptoms- dizziness, bladder complaints, impotence etc may be prominent & early in MSA, neurodegenerative disease

Alcohol responsiveness, essential tremor is characteristically response to alcohol

Specific distribution-• Chorea/ athetosis - mainly in the distal groups

• Hemiballismus- mainly proximally

• Parkinsons disease- mainly unilateral & asymmetric

• Blepherospasm- affect both eye

Specific action & relationship to voluntary movement-• task specific tremor (intention tremor) during pick up a

glass of water

• Task specific dystonia eg: Writers cramp, musiciancramp

Speed of movement-

Rhythm-Continuous – tremor Intermittent – astrexis

Relationship to sleep- Palatal myoclonus, segmental myoclonus, fasciculation & myokymia, persist during sleep , Dystoniadiminished on sleep

Supresibility- tics may be voluntary suppressed

Slow Intermediate Fast

Parkinsonism Chorea Myoclonus

Dystonia Tremor Tics

Athetosis

Aggravating or precipitating factor- stress and anxiety worsen all movement disorder • Myoclonus may be triggered by specific stimuli-

sudden loud noise or touch

• Carbohydrate heavy meal, fatigue may precipitateparoxysmal dystonia

Associated sensory symptom- RLS associated with pain or discomfort, tics may be associated with vague discomfort or abnormal sensation

Ameliorating factor- alcohol dramatically improved essential tremor and myoclonic dystonia

2nd commonest neurodegenerative disease of neurons in the nigrostrialdopamine system

Clinical Features of Parkinson's Disease

Cardinal Features Other Motor Features Nonmotor Features

Bradykinesia

Rest tremor

Rigidity

Gait disturbance/postural

instability

Micrographia

Masked facies

(hypomimia)equalize

Reduced eye blink

Soft voice (hypophonia)

Dysphagia

Freezing

Anosmia

Sensory disturbances

(e.g., pain)

Mood disorders (e.g.,

depression)

Sleep disturbances

Autonomic disturbances

Orthostatic hypotension

Gastrointestinal

disturbances

Genitourinal disturbances

Sexual dysfunction

Cognitive

impairment/Dementia

1- Static tremors

Rhythmic occuring at a rate of 4-8 / second

May start in one hand and spread to other

parts of the body

Characteristically pill-rolling movements

between the thumb and the forefinger are

seen

Tremors increase with emotional, anxiety and

fatigue and disappear during sleep and during

active voluntary movements

2- Rigidity of the musclesMore proximal than distalFlexors are affected more than extensorOn clinical examination the resistance may be

continuous throughout the act to the samedegree (lead pipe rigidity) or interrupted bythe tremors (cog wheel rigidity)

Stiffness of the limbs develops causingdifficulty in starting movements and walking(slow, shuffling gait)

3- Akinesia: Loss of emotional and associative movements resulting in:

Immobile face with infrequent blinking (mask face)

Monotonous speech

Loss of swinging of the arms during walking

Pathologically, the hallmark features of PD are degeneration of dopaminergicneurons in the substantia nigra pars compacta (SNc), reduced striatal dopamine,and intracytoplasmic proteinaceous inclusions known as Lewy bodies.

neuronal degeneration with inclusion body formation can also affect cholinergicneurons of the nucleus basalis of Meynert (NBM), norepinephrine neurons of thelocus coeruleus (LC), serotonin neurons in the raphe nuclei of the brainstem, andneurons of the olfactory system, cerebral hemispheres, spinal cord, andperipheral autonomic nervous system.

Indeed, there is evidence that pathology begins in the peripheral autonomicnervous system, olfactory system, and dorsal motor nucleus of the vagus nerve inthe lower brainstem, and then spreads in a sequential manner to affect the upperbrainstem and cerebral hemispheres. These studies suggest that dopamineneurons are affected in midstage disease.

Several studies suggest that symptoms reflecting nondopaminergic degenerationsuch as constipation, anosmia, rapid eye movement (REM) behavior sleepdisorder, and cardiac denervation precede the onset of the classic motor featuresof the illness.

Differential Diagnosis of Parkinsonism

Parkinson's Disease

Genetic

Sporadic

Dementia with Lewy

bodies

Atypical

Parkinsonisms

Multiple-system

atrophy

Cerebellar type

(MSA-c)

Parkinson type

(MSA-p)

Progressive

supranuclear palsy

Corticobasal

ganglionic

degeneration

Frontotemporal

dementia

Secondary

Parkinsonism

Drug-induced

Tumor

Infection

Vascular

Normal-pressure

hydrocephalus

Trauma

Liver failure

Toxins (e.g.,

carbon monoxide,

manganese,

MPTP, cyanide,

hexane, methanol,

carbon disulfide)

Other Neurodegenerative

Disorders

Wilson's disease

Huntington's disease

Neurodegeneration with

brain iron accumulation

SCA 3 (spinocerebellar

ataxia)

Fragile X–associated

ataxia-tremor-

parkinsonism

Prion disease

Dystonia-parkinsonism

(DYT3)

Alzheimer's disease with

parkinsonism

Modern immunocytochemical techniques and genetic findings suggest that Parkinson-plus syndromes can be broadly grouped into 2 types: synucleinopathies and tauopathies. Clinically, however, 5 separate Parkinson-plus syndromes have been identified, as follows:

1. Multiple system atrophy2. Progressive supranuclear palsy3. Parkinsonism-dementia-amyotrophic lateral sclerosis complex4. Corticobasal ganglionic degeneration5. Diffuse Lewy body diseaseParkinson-plus syndromes respond poorly to the standard

treatments for Parkinson disease (PD).

In addition to lack of response to levodopa/carbidopa(Sinemet) or dopamine agonists in the early stages of the disease, other clinical clues suggestive of Parkinson-plus syndromes include the following:

History and Examination Features Suggesting Diagnoses Other Than Parkinson's

Disease

Symptoms/Signs Alternative Diagnosis to Consider

History

Falls as the first symptom PSP

Exposure to neuroleptics Drug-induced parkinsonism

Onset prior to age 40 If PD, think genetic causes

Associated unexplained liver disease Wilson's disease

Early hallucinations Lewy body dementia

Sudden onset of parkinsonian symptoms Vascular parkinsonism

Physical Exam

Dementia as first symptom Dementia with Lewy bodies

Prominent orthostasis MSA-p

Early dysarthria MSA-c

Lack of tremor Various Parkinson's-plus syndromes

High frequency (8–10 Hz) symmetric tremor Essential tremor

Diagnosis of PD

clinical examination

No disease-specific biological marker

available

Positron Emission Tomography (PET)

or Single-photon Emission Computed

Tomography (SPECT) with

dopaminergic radioligands

Exclusion of several causes of

secondary Parkinsonism

(A) Dopamine Carbidopa/l-dopa Dopamine agonists: Apomorphine(off phenomenon), s/c, i.v.

CabergolineRopinirole, Pramipexole

COMT inhibitors: Entacapone MAO Inhibitors: e.g. Selegiline (B-type) Inhibitors of dopamine re-uptake: Amantadine

(2) Acetylcholine Anticholinergic

Antihistaminics

Drugs commonly used in the treatment of Parkinson disease

MEDICATION

STARTING

DOSE

TARGET

DOSE MAIN BENEFIT SIDE EFFECTS

Carbidopa-L-dopa

(Sinemet)

25/100 tid

empty

stomach

Up to 50/250

q 3 h

Reduction of tremor and

bradykinesia; less effect on

postural difficulties

Nausea, dyskinesias, orthostatic

hypotension, hallucinations,

confusion, arrhythmia

Controlled release

carbidopa-L-dopa

25/100 tid Up to 50/200

q 4 h

Dopamine agonists

Ropinirole(D3) 0.125 mg

tid

0.5 to 1.5

mg/day

Moderate effects on all

aspects; reduced motor

fluctuations of L-dopa,

neuroprotective, neurotrophic

Orthostatic hypotension,

excessive and abrupt

sleepiness, confusion,

hallucinations, impulse control

disorders

Pramipexole(D2) 0.25 mg tid 8 to 24

mg/day

Glutamate agonist

Amantadine

(Symmetrel)

100

mg/day

100 mg bid-tidSmoothing of motor

fluctuations

Leg swelling, congestive heart

failure, prostatic outlet

obstruction, confusion,

hallucinations, insomnia

Anticholinergics

Benztropine

(Cogentin)

0.5 mg per

day

Up to 4 mg

per day

Tremor reduction, less effect

on other features, drug

induced parkinsonism

Atropinic effects: dry mouth,

urinary outlet obstruction,

confusion and psychosisTrihexyphenidyl

(Artane)

0.5 mg bid Up to 2 mg tid

MAO-B inhibitor

selegiline, 5mg/day bd Neuroprotection, adjuntive

therapy

Insomnia

Rasagiline 1mg/day

COMT inhibitors

Entacapone 200 mg with L-dopa Urine discoloration, diarrhea,

increased dyskinesias

Stereotactic neurosurgery: pallidotomy, thalamotomy ,sub thalamotomy

Indications1.idiopathic parkinsons2.levodopa unhelpful3.intractable PD4.drug dyskinesias

Deep brain stimulation: dyskinesia Tissue transplantation: Experimental transplantation of fetal

or autologous dopamine-containing adrenal medulla or stemcell research has produced no promising results in PD to date.

Physiotherapy and physical aids Neuropsychiatric aspects: Cognitive impairment and

depression are common as PD progresses. SSRIs are thedrugs of choice for depression.

Sudden, brief, rapid, jerky, purposeless, non-

repetitive, involuntary movement

Most characteristically in distal parts of upper

extremity but may also involved proximal part,

lower extremity, trunk, face & tongue

PATHOLOGY

Damage to caudate nucleus

Disease characterized by chorea: Inherited disorder: Huntington disease, wilson

disease, benign hereditry chorea,neuroacanthocytosis

Infectious causes: Rheumatic chorea(sydenham chorea), HIV disease

Structural lesion of the basal ganglia- infarct,neoplasm, trauma

Chorea of systemic disease: SLE, thyrotoxicosis, polycythemia vera, hyperosmolar non-ketotic hyperglycemia

Pregnancy (chorea gravidarum)Drugs: Neuroleptics, OCP, excessive dose of

levodopa or dopamine agonist, phenytoincocaine

Hypotonia Pronator sign Milkmaid’s grip Spooning sign Pendular knee jerk “hung up reflex” Lizard tongueIncreased by excitement, diminished by sleepSydenham chorea (Saint vitus dance) more common in

female and childhood (5-15yrs), associated with prior exposer to group a streptococcal infection, late manifestation

Huntington's disease progressive fatal autosomaldominant disorder characterized by motor, behavioral & cognitive dysfunction, in early stages chorea is focal or segmental but it progress over time to involve multiple body region

Etiology HD is caused by an increase in the

number of polyglutamine (CAG)repeats (>40) in the coding sequenceof the huntingtin gene located on theshort arm of chromosome 4. The largerthe number of repeats, the earlier thedisease is manifest.

Treatment multidisciplinary approach Dopamine-blocking agents may control

the chorea. Tetrabenazine depression and anxiety can be greater

problems, and patients should betreated with appropriate antidepressantand antianxiety drugs and monitored formania and suicidal ideations.

Psychosis can be treated with atypicalneuroleptics such as clozapine,quetiapine, and risperidone

There is no adequate treatment for thecognitive or motor decline

Slow, distal, purposeless, writhing involuntarymovement

They are more sustained and larger in amplitudethan those in chorea

The mainly involved the extremities (distalportion, fingers & hands) face, neck & trunk

Movement are characterized by any combinationflexion, extension, abduction, pronation, &supination often alternating and in varyingdegree

Predominant pathologic changes are in theputamen

Causes: cerebral palsy, perinatal injury to basal ganglia, wilson disease

Choreoathetosis: the movement live between chorea & athetosis in rate and rhythmicity eg: cerebral palsy ( Neonatal jaundice)

Pseudoathetosis: (sensory athetosis) undulating & writhing movement of extremities due to loss of position sense as a result of parietal lobe lesion, tabesdorsalis, peripheral nerve disease

A wild, flinging, large amplitude movements on one side of the body

Proximal upper limb muscles predominantly affected

Ballastic movement of hemiballismus resemble that of chorea but are more pronounced, rapid & forceful

Movement ceaseless during the walking state and disappear only with the deep sleep

Usually self limiting and tends to resolve spontaneously after weeks to months

Due to infarction or hemorrhage in the regions of contralateral subthalamic nucleus, results in disinhibition of the motor thalamus and cortex resulting in contralateralhyperkinetic movement.

Treatment: Dopa blocking agentPallidotomy can be done.

Sustained or repetitive involuntary muscle contraction leading to twisting

movements and abnormal posture

Can involve individual muscle or multiple muscle groups.

Often affect the extremities neck, trunk, eyelids, face & vocal cords

Dystonic movements are patterned tending to recur in same location

When duration is very brief less than one second- dystonic spasm, when

for several seconds, dystonic movement & when prolonged minutes to

hours- dystonic posture

Pathophysiology of Dystonia

not known.

co-contracting synchronous bursts of agonist and antagonist muscle groups

due to loss of inhibition at multiple levels of the nervous system as well as

increased cortical excitability and reorganization.

Attention has focused on the basal ganglia as the site of origin of at least

some types of dystonia as there are alterations in blood flow and metabolism

in basal ganglia structures. Further, ablation or stimulation of the globus

pallidus can both induce and ameliorate dystonia.

Dystonia can be generalized or focal: primary orsecondary

Generalized dystonia is mainly primarydystonia involving larger portion of body oftenproducing distorted posture of limbs & trunk(Torsion dystonia)

Idiopathic torsion dystonia (dystonia musculormdeformance) is predominantly childhood onsetform of dystonia with autosomal dominantpattern of inheritance

May starts distally usually in the foot in theplanter flexation & inversion & speed to oppositeside, upper extremity trunk & face

There is peculiar axial involvement of spine(twisting)

Dopa responsive dystonia ( Segawa variant) dominantly inherited form of dystonia in early childhood 1-12yrs typically present with foot dystonia resulting in gait disturbance and there is excellent response to small doses of levodopa.

Diurnal variation, worsen with day progresses

Focal dystonia is a most common, 4th to 6th

decade and more common in female:• Blephero spasm• Oromandibular dystonia• Spasmodic dysphonia• Cervical dystonia• Limb dystonia (writer’s cramp)

Secondary dystonia:Due to drugs: Neuroleptics,

(Phenothiazine, Butyrophenone), chroniclevodopa treatment in parkinsons disease

Discrete lesion in the stratum, palladum,thalamus, cortex & brain stem

Dystonia plus syndrome:May occur in the neurodegenerative

condition (Huntington disease, Wilsondisease, parkinson disease, corticobasaldegeneration & progressive supranuclearpalsy)

symptomatic Levodopa should be tried in all cases of childhood-onset dystonia to

rule out DRD. High-dose anticholinergics (e.g., trihexyphenidyl 20–120 mg/d) may

be beneficial in children, but adults can rarely tolerate high doses because of cognitive impairment with hallucinations.

Oral baclofen (20–120 mg), Tetrabenazine (the usual starting dose is 12.5 mg/d and the average treating dose is 25–75 mg/d) may be helpful in some patients, but use may be limited by sedation and the development of parkinsonism.

Botulinum toxin has become the preferred treatment for patients with focal dystonia, particularly where involvement is limited to small muscle groups such as in blepharospasm, torticollis, and spasmodic dysphonia.

Surgical therapy is an alternative for patients with severe dystoniawho are not responsive to other treatments. Peripheral procedures such as rhizotomy and myotomy were used in the past to treat cervical dystonia, but are now rarely employed. DBS of the pallidumcan provide dramatic benefits for patients with primary DYT1 dystonia

Supportive treatments such as physical therapy and education are important and should be a part of the treatment regimen.

Sudden, brief (<100ms) shock like, jerkyinvoluntary movement consisting of single orrepetitive muscle discharges

Myoclonus is seen principally in the muscles ofextremities and trunk but the involvement is oftenmultifocal, diffuse or wide spread

Can often spontaneously, association withvoluntary movement (action myoclonus) or inresponse to external stimulus (reflex or startlemyoclonus)

Myoclonic jerks defer from tics in that theyinterfere with normal movement and notsuppressible

Symptomatic causes of myoclonus: Metabolic endogenous- Hypoxia, uraemia,

hepatic failure, hypoglycemia, hyponatraemia,non-ketotic hyperglycemia

Degenerative: Alzheimer’s disease, Huntingtondisease, multisystem atrophy, corticobasaldegeneration

Infectious: Creutzfeldt –Jakob disease, EBV etc Autoimmune: Multiple sclerosis Neoplastic: Neuroblastoma, paraneoplastic

disorders (ovarian, lung & breast) Frequently associated with epilepsy, electric

shock, heat stroke Drugs: Amantadine, lithium, metoclopramide,

levodopa & dopamine agonist, cocaine,strychnine

Opsoclonus- Myoclonus (Kinsbournesyndrome)- Dancing eye & dancing feet

Due to the post infectious encephalopathy or as aparaneoplastic syndrome due to neuroblastoma

Palatal myoclonus- involuntary rhythmic movementof soft palate and pharynx the movements aregenerally not influenced by drugs or sleep palatalmyoclonus occur with lesions involving theconnections between the inferior olivary, dentate &red nuclei

Astrexis: particularly in hepatic encephalopathy,negative myoclonus inability to sustained normalmuscle tone presenting with slow & irregularflapping motion

Acute- Dystonia is most common acute drugreaction can develop within minutes of exposuretypically generalized in children and focal in adults

Treatment: parenteral administration ofanticholinergics (benztropine or diphenhydramine)or benzodiazepines (lorazepam or diazepam).

Subacute- Akathisia is commonest reaction itconsist of motor restlessness within in need to moveand that to elevated by movement.

Treatment: Removing the offending agent.If notpossible, give benzodiazepines, anticholinergics,blockers, or dopamine agonists for symptomaticimprovement.

Chronic- Tardive syndrome after months to years after initiation of treatment A typically comprises choreiform movement involving the mouth lip, tongue, and in severe cases trunk, limbs and respiratory muscles can be affected Is more common in elderly women & with underlying organic cerebral dysfunction (Schrizophrenia)

Brief, repeated, sterotyped muscle contraction that often suppressible

Quick, irregular, seemingly purposeful act but relatively involuntary

Patient have some degree of awareness of movement and in response to urge of some compelling inner forces

Exaggerated by emotional strain and tension and stop during sleep

May involved any portion of body

Eg: Repetitive blinking, facial contortions, shoulder shrugging, also involved vocal tract producing throat clearing

Gilles de la Tourette Syndrome characterized by multiple motor tics and vocalizations

Motor tics can be simple/ complex & vocal tics can be simple (grunting) or complex (echolalia)

Tourette syndrome is a disease of early childhood in the first decade and mainly in Boys an associated with some regressive behaviour

Contrary to dopamine, it can pass into the brainwhere it is decarboxylated into dopamine

Levodopa is combined with a peripheral L-AAdecarboxylase inhibitor e.g. carbidopa orbenserazid to delivery of l-dopa into the brain peripheral adverse effects of dopamine

Carbidopa if peripheral adverse effects areprominent

It has dramatic initial response, decreases withtime (wear off) due to the progressive loss ofneurons

Combined with carbidopa is the most

potent oral therapy for Parkinson’s disease

Symptoms of Parkinson’s disease but

does not stop the progression

(deterioration) of the disease i.e.

Symptomatic treatment

From the third year its efficacy declines

Peripheral:• GIT: Nausea & Vomiting• CVS: Orthostatic hypotension, Dysrhythmias• Blood dyscrasias & Positive reaction to Coombs

test• Mydriasis and Brownish discoloration of urine &

saliva CNS Effects:

• Visual & Auditory hallucinations & vivid dreams• Dyskinesias: opposite of Parkinsonian symptoms• Mood changes, depression & Anxiety

Long-term levodopa Complications:• Wearing off (fluctuations), Dyskinesias

Ergot alkaloid derivatives:

Bromocriptine & Pergolide

Non-ergot alkaloid derivatives:

Pramipexole & Ropinirole

Have longer duration less fluctuationHave less tendency to induce dyskinesia Ineffective in patients not responding to

leveodopaCan be used in early cases to delay use

of levodopa (in levodopa-naïve patients)& in advanced cases to augment

levodopa and to decrease fluctuations to its response

Pergolide is more potent than Bromocriptine Their side effects limit their use and slow rapid

build up of doses (over 2-3 Months)

Side effects include levodopa side effects in addition to spasmogenicity & fibrosis (of serous membranes)

Pramipexole & Ropinirole

Pramipexole: is cleared by renal

excretion

Ropinirole: is cleared by metabolism

Side effects as levodopa with less

dyskinesia and fluctuation and

No spasmogenicity and

fibrosis

Antiviral (influenza) drug

The mode of action is unknown • # NMDA glutamate receptors (the primary action)• # Muscarinic receptors• Increases release of dopamine

It has little effect on tremors &

Tolerance develops rapidly

Augment the effect of dopamine Weak and play an adjuvant role They are the same in efficacy but with some inter-

individual variation in responseSide effects: Mood changes Xerostomia, blurred vision, constipation, urinary

retention Hallucination, confusion

C/I: in glaucoma, SPH, Pyloric stenosis

Parkinson-plus syndromes respond poorly to the standard treatments for Parkinson disease (PD).

In addition to lack of response to levodopa/carbidopa (Sinemet) or dopamine agonists in the early stages of the disease, other clinical clues suggestive of Parkinson-plus syndromes include the following: Early onset of dementia

Early onset of postural instability

Early onset of hallucinations or psychosis with low doses oflevodopa/carbidopa or dopamine agonists

Ocular signs, such as impaired vertical gaze, blinking on saccade,square-wave jerks, nystagmus, blepharospasm, and apraxia of eyelidopening or closure

Pyramidal tract signs not explained by previous stroke or spinal cordlesions

Autonomic symptoms such as postural hypotension and incontinenceearly in the course of the disease

Prominent motor apraxia

Alien-limb phenomenon

Marked symmetry of signs in early stages of the disease

Truncal symptoms more prominent than appendicular symptoms

Absence of structural etiology such as a normal-pressure hydrocephalus(NPH)

Tremor is rhythmic, involuntary, purposeless oscillatory movement of body part due to intermittent muscle contraction

Types: i. Rest ii. Postural iii. Intention Rest Tremor: is maximum at rest & becomes less

prominent with activity eg: parkinson disease, Postural Tremor: is maximum while limb posture

is actively maintained against gravity (arm outstretched) eg: Essential tremor, enhanced physiologic tremor,

Intention Tremor: Most prominent during voluntary movement toward a target eg: cerebellar disease

Etiology: Parkinsonism

Essential tremor

Physiologic tremor

Alcohol

Anxiety

Thyrotoxicosis

Cerebellar disease

Wilson disease

Red nuclear tremor

Drugs (-2agonist, sympathomimetics,methylxanthine, amphetamine, anticonvulsant,

Poison (Mercury, MPTP)

Essential tremor: Most common involuntary movement disorder

High frequency, coarse mainly distal upper extremity & later become bilateral symmetrical

Maximum when trying to maintain a posture Autosomal dominant pattern of inheritance Characteristically improve with alcohol & -

blocker

Parkinsonism is a slow (4-6 Hz) coarse, rest tremor typically appears unilaterally, pill rolling tremor

Physiologic Tremor: In normal individual 8-12Hz, mainly young adults

Cerebellar tremor: intention tremor,coarse & irregular

Thyrotoxic tremor: fine & rapid but maybe complicated by choreiform involuntarymovement

Red nuclear tremor: the severe, largeamplitude, slow 2-5 Hz, involve bothproximal & distal muscle present at restbut made worse with action

Fine rapid, flickering or vermicular twitching

movements due to contraction of a bundle or

fasciculus of muscle fibers

Fasciculations are much more gross than

fibrillation and can be seen through intact skin

and this continue during sleep

Exaggerated by fatigue, cold, cholinergic drugs,

caffine

Characteristic feature of motor neuron disease,

anterior horns cell disease

Involuntary, spontaneous, localized, transient or persistent quivering movement that affect a few muscle bundles with in a single muscle

Coarse, slower, worm like, usually more prolonged and involved in wide local area than fasciculation

Not affected by motion or position and persist during sleep

Most commonly present in orbicularis oculi Generalized myokymia (Isaac’s syndrome)

generalized muscle stiffness and persistent contraction due to underlying continuous muscle fiber activity

Slow 2-3Hz rhythmic alternating movement

resemble tremor

Wide spread involvement, may involved multiple

body parts

Absent during sleep

May be intermittent or continuous, synchronous

or asynchronous

Eg: CNS whipple’ disease