Diseases of the Extrapyramidal System PDF

Neurology Diseases of the Extrapyramidal System Introduction The control of voluntary movement is affected by the interaction of: 1. Pyramidal 2. Cerebellar 3. Extrapyramidal ✓ All theses systems interconnecting with each other as well as project...

Neurology Diseases of the Extrapyramidal System Introduction The control of voluntary movement is affected by the interaction of: 1. Pyramidal 2. Cerebellar 3. Extrapyramidal ✓ All theses systems interconnecting with each other as well as projecting to the ant. horn region or CN motor nuclei. The term extrapyramidal system refers to a complex neural network composed of several well defined nuclei called basal ganglia and their connection to the cortex, brainstem and spinal cord. There are four important basal ganglia: ▪ Caudate nucleus. ▪ Lentiform (globus and putamen) nucleus. ▪ Substantia nigra. ▪ Subthalamic nucleus. The connections between components of extra pyramidal system and other parts of the brain are complex However, certain simple observations can be made:- A) The thalamus plays a vital role in projecting information from the basal ganglia to the motor vortex and back B) The motor cortex projects through the striatum to other basal ganglia C) The final common pathway for basal ganglia motor function is the corticospinal or pyramidal tract.  The most common of extrapyramidal syndromes. 1) Parkinson’s disease. 2) Rheumatic or Sydenham’s chorea. 3) Dystonia and athetosis. 1  Neurology (1) Parkinson’s disease It was first described by James Parkinson on 1817 as shaking palsy. Parkinson’s disease occurs in 1% of people over the age of 60 years. It is manifested by the following: ▪ Tremors. ▪ Rigidity. ▪ Hypokinesis (decreased voluntary movements). ▪ Good response to levodopa.  Etiology: ▪ The cause of Parkinson's disease Gene mutations have been identified in young onset and familial cases (Synuclein, Parkin and LRRK 2). ▪ The nigrostraital pathways depends on both acetylecholine and dopamine, acetylecholine exerts a net excitatory effect, while dopamine exerts a net inhibitory effect on the neuronal output of the basal ganglia. ▪ In Parkinson’s disease, the substantia nigra is depleted from dopamine leaving the output under the excitatory influence of acetylecholine. ▪ Parkinson’s disease occurs as a primary degeneration in the substantia nigra of unknown etiology, degeneration of the substantia nigra might be triggered by repeated head trauma as in professional boxers, other parkinsonian syndromes include: 1. Post – encephalitic (encephalitis lethargia). 2. Drug induced following prolonged phenothiazine and reserpine administration. 3. Carbon monoxide poisoning. 4. Inborn error of copper metabolism in cases of Wilson’s disease. 5. Vascular lesions affecting substantia nigra.  Incidence: ▪ Age: 60 yrs old, incidence peaks in mid-70s then declines ▪ Familial incidence occurs in 5 % 2  Neurology  Pathology: ▪ The substantia Nigra (SN) contains pigmented cells neuromelanin) which gives it a characteristic black appearance (macroscopic). ▪ Theses are degenerated and lost in Parkinson's disease And SN become pale. ▪ Remaining cells contain atypical eosinophilic inclusions in the cytoplasm called Lewy bodies.  Clinical Picture: Age at onset: the fifth or sixth decades. The onset is insidious and the course is slowly progressive. 1. Tremors: ▪ Firstly involves the fingers and then extend to the proximal parts of the arm, later it may affect the leg and rarely involve the head. ▪ Coarse, rhythmic (3-8 cycle per second) and have a pill rolling or money counting feature. ▪ Appear during rest (static) and decrease during action or intention for voluntary acts. ▪ Increase by emotional upset and disappear during sleep. ▪ As rigidity increases, tremors tend to decrease. In some case they may not appear at all. 2. Rigidity: ▪ Which is an increase in the resistance to the passive stretch of the muscle during flexion or extension of the joint (lead-pipe rigidity), but because of the tremors, rigidity is interrupted and has a (cogwheel character). ▪ Rigidity is responsible about the generalized flexion attitude of the patient’s body during walking or standing. 3. Hypokinesis (Bradykinesia): ▪ It is defined as decrease and delay in initiation and slowness of voluntary movements. ▪ It the first and most disabling symptoms of Parkinson’s disease. ▪ There is often difficulty in rising from a chair and in starting walking leading to short-stepped and shuffling gait. ▪ Also there is a loss of arm swinging during walking. ▪ Hypokinesia is responsible about many other features of Parkinson’s disease as infrequent blinking of the eye, low monotonous speech and masked face. 3  Neurology 4. Postural instability: ▪ Often cited as the fourth core features of Parkinson's disease but it is not often an early symptom. ▪ The patients has tendency to topple forwards or backwards if pushed or pulled (propulsion & retropulsion) ▪ Postural instability and gait failure are the most disabling features of Parkinson's disease and the most resistant to dopamine replacement therapy.  Diagnosis: ▪ The diagnosis of Parkinson’s Disease is difficult in early stages. ▪ New tremors in middle age causes particular difficulty → Senile/ essential/ metabolic tremors is generally absent at rest and worsened by movement. ▪ Functional imaging (PET&SPECT) improved diagnostic accuracy.  Differential Diagnosis: 1. Essential or familial tremor: Appear at younger age, there may be a positive family history, there is no rigidity or hypokinesis. 2. Hypothyroidism many produce apathetic and emotionless facies similar to that of parkinsonism. 3. Cerebellar tremors are kinetic in nature and associated with other signs of cerebellar dysfunction. 4. Metabolic: as with liver or chronic renal failure.  Treatment: 1. Anticholinergic drugs: ▪ They produce little improvement of tremors and rigidity, they don’t have any effect on hypokinesis. ▪ They cause dryness of mouth, palpitation, blurring of vision, urinary retention and confusion in elderly patients. ▪ Benzotropine (cogentin) is commonly used in doses of 2 mg /8 hours. 2. Dopamine replacement "Levodopa": ▪ Dopamine is most effective against hypokinesis, it does not cross the blood brain barrier, its precursor Levodopa is administered orally in tablet forms. ▪ The main side effects are nausea, vomiting and cardiac arrhythmia. ▪ Addition of Carpidopa (dopamine decarboxylase inhibitor) to Levodopa, reduces its extracerebral degradation and increases its concentration in the brain. ▪ The usual dose is 250 mg Levodopa + 25 mg Carpidopa (Sinemet 275) twice daily with gradual increase until the maximum improvement is reached, the dose should not exceed 2 grams per day. ▪ After prolonged use, there may be fluctuation of symptoms each day. This phenomenon is called (on-off) effect of dopamine and it is due to fluctuation of blood and brain level of the drug. 4  Neurology 3. Dopamine receptor agonists: ▪ They act by stimulating striato-nigral dopamine receptors. ▪ Bromocriptin (parlodel) is commonly used orally in initial dose of 2.5 mg daily, and then increased slowly over several weeks up to 20 mg per day. ▪ It has similar side effects like that of dopamine. ▪ Dopamine agonists are used to reduce the dose of dopamine. 4. Amantadine hydrochloride: ▪ It exerts its action through stimulation of endogenous dopamine. ▪ It has a weak effect on tremors and hypokinesis. ▪ Its usual dose is 100 mg every 12 or 8 hours. ▪ Its main side effects are vasodilatation, edema, and confusion and in rare cases may induce seizures. 5. Surgical treatment: ▪ In rare cases with unilateral tremor refractory to medical treatment, stereotactic thalamatomy may be helpful. ▪ Hemiplegia may occur during surgery due to accidental damage of the pyramidal tract in the internal capsule. (2) Rheumatic or Sydenham’s chorea  Sydenham Chorea was described in the 17th century by Dr/ Thomas Sydenham and was associated with rheumatic fever  Definition: ▪ Chorea is defined as an irregular, low amplitude, rapid, jerking movement of the extremities and the face ▪ Patients often disguise their movements into apparently purposeful actions ▪ Larger amplitude proximal choreiform movements may be violent and are referred to as ballism ▪ Rheumatic chorea is an acute disease occurs in children and adolescence and affects girls more frequently than boys. ▪ It often follows a streptococcal upper respiratory tract infection, but in many patients such a history is negative. ▪ In most cases, chorea affects one side of the body more than the other. ▪ Pregnancy may trigger relapses in affected females.  Etiology: ▪ It is triggered by a preceding infection with group A beta streptococcus ▪ It is thought that it is due to an immunological cross reaction between the strept M protein and the brain epitopes causes an autoimmune encephalitis ▪ Contrary to Parkinson’s disease, chorea occurs as a result of increased dopamine activity in the basal ganglia. 5  Neurology  Clinical Features: ▪ It occurs mainly in children and adolescents, more often in girls. ▪ There is subacute onset of chorea, hypotonia, muscular weakness and often prominent mental changes with emotional and behavioral abnormalities. ▪ It is unilateral in 20% and some patients develop frank hemiballismus. ▪ Behavioral and psychological changes include personality changes, obsessive compulsive behavior and irritability. ▪ Emotional changes, aggression, anxiety and mood disturbances. ❑ There are three cardinal features of chorea: 1. Hypotonia: sometimes is remarkable and causes paralysis, hence the name paralytic chorea. 2. Involuntary movements: they are jerky, irregular and seem to be purposive, affect mostly facial muscles, hands and arms. Choriform movements increase by emotional stress and disappear during sleep. 3. Hyperkinesis: Increased associative movements or hyperkinesis, this disorder produces increased facial grimaces and hand movement during talking and also causes (contrary to parkinsonism) exaggerated arm swinging during walking. Very frequently the child has a marked degree of psychological upset, causes him to withdraw and stop talking to others. If involuntary movements involve respiratory and laryngeal muscles, dysartheria may occur. ❑ The following are important diagnostic signs for chorea: 1. Pronator sign: the extended arm, when elevated above the head, the arm of the affected side is hyperpronated. 2. Tongue sign: the patient can’t keep his tongue protruded for long time, he may clench it by his teeth in order to do that.  Treatment: ▪ Rheumatic chorea is a relatively benign and self limiting condition, in many cases involuntary movements cease spontaneously within few days or weeks. ▪ However, in few cases relapses tends to follow group A streptococcal infection of the upper respiratory tract. ▪ In addition to rest and psychological support, the following drugs are effective in controlling movement disorder and prevent relapses. 1. Haloperidol: It decreases dopamine activity in the basal ganglia, the initial dose is 1.5 mg / 12 hours (orally) the dose may be gradually increased until involuntary movement control is achieved. 2. Diazepam: In severe cases with marked involuntary movements, the child is severely exhausted and should be hospitalized and treated by IM diazepam in a dose of 0.05 mg/kg body weight. 3. Penicillin: Initial course for 7 days for streptococcal throat infections. 4. Steroids: In some resistant cases, steroids may be needed. 1 mg dexamethason every 8 hours for 5 or 6 days. 6  Neurology (3) Dystonia and Athetosis  Definition: ▪ Dystonia refers to sustained muscle contraction, that may cause twisting movements, abnormal posture or tremiouls movement, they are frequently repetitive. ▪ Agonist and antagonist muscles contract simultaneously to produce dystonic movements. ▪ Dystonic movements are typically twisting and involve proximal more than distal muscles ▪ Dystonic movements are often action specific, so that may erroneously suggest a psychiatric disorder ▪ Sometimes, there is overflow dystonia in which dystonic movements appear in other body parts which are not normally involved in the execution of a particular movements  Etiology: ▪ Dystonia and athetosis usually result from birth injury, kernictrus, hypoxia or encephalitis. ▪ Adult onset dystonia is either idiopathic or transmitted as autosomal dominant or recessive disorder.  Management: ▪ Some patients respond to a gradually increasing dose of anticholinergic drugs as benzotropine (Cogentine) and benzodiazepin. ▪ In selected sever cases, involuntary movements can be reduced by neuromuscular blockage using local injection of diluted botulinum toxins. 7