Extrapyramidal Disorders PDF

NEUROLOGY EXTRAPYRAMIDAL DISEASES Facebook: @walid reda ashour 1  EXTRAPYRAMIDAL DISEASES PARKINSONISM & PARKINSON’S DISEASE Definition: It's a clinical syndrome characterized by rest tremor, bradykinesia, rigidity. Essentials of diagnosis: 1) Tremor at rest 2)...

NEUROLOGY EXTRAPYRAMIDAL DISEASES Facebook: @walid reda ashour 1  EXTRAPYRAMIDAL DISEASES PARKINSONISM & PARKINSON’S DISEASE Definition: It's a clinical syndrome characterized by rest tremor, bradykinesia, rigidity. Essentials of diagnosis: 1) Tremor at rest 2) Bradykinesia 3) Rigidity. 4) Loss of postural reflexes. 5) Flexed posture 6) Freezing. Causes of Parkinsonism: 1) Idiopathic: Parkinson’s Disease. 2) Secondary Parkinsonism: Deficiency of Dopamine in the brain without structural changes in the substantia nigra or basal ganglia. - Vascular (Arteriosclerotic). - Post-encephalitic. - Hydrocephalus. - Drug-induced: i.e. Antipsychotics, antiemetics & other dopamine-blocking agents. - Toxic (- Carbon Monoxide poisoning - Manganese poisoning). 3) Degenerative Disorders: - Alzheimer’s disease -Parkinson-dementia complex. 4) Genetic Disorders: - Wilson’s disease (consider in all cases < 50 years). - Huntington’s disease. - Dopa-responsive dystonia. 2 5) Traumatic: repeated trauma to the head as in boxers (very rare).  EXTRAPYRAMIDAL DISEASES PARKINSON’S DISEASE (PD) It's a progressive neurodegenerative disorder clinically characterized by Rest Tremor, Bradykinesia & Rigidity. As the disease advances, patients may experience gait & balance disturbances as well as non-motor features including dementia. Aetiology: Unknown. Risk factors: Age: Increasing age is the single greatest risk factor (> 50 y). Sex: Males > females 2:1. Rural residence, farming. - Contact with pesticides & herbicides. N.B. Decrease risk associated with caffeine. Pathophysiology of PD: -There is degeneration (neuronal cell loss) of the pigmented cells (neuromelanin) of the substantia nigra (SN), which becomes pale. The basal ganglia are also affected. When cell loss exceeds 60%, there is a critical deficiency of dopamine in the forebrain, resulting in motor symptoms of 3 PD.  EXTRAPYRAMIDAL DISEASES Clinical Features of Parkinsonism & PD: 1- Rest (Static) Tremor: Regular, rhythmic & occur at the rate of 4-8/second. They Begin Unilaterally in the UL & spread to all 4 limbs. They give the hand the Pill-Rolling Posture with the thumb moving rhythmically back & forward on the palm. Increase with emotional stress & fatigue & disappear during sleep & voluntary movements. 2- Rigidity (Hypertonia): Affecting the proximal more than the distal muscles. Affecting more the flexors of the neck, trunk limbs resulting in the Flexion Attitude. It may be present throughout the act to the same degree → Lead Pipe Rigidity; or it may be interrupted by the tremors → Cog Wheel Rigidity. Causing difficulty in starting the act of walking (Freezing) with slow, Shuffling (Short Steppage) Gait with propulsion. 4  EXTRAPYRAMIDAL DISEASES 3- Bradykinesia: slowness of initiation of voluntary movement with progressive reduction in speed & amplitude with repetition. 4- Loss of emotional & associative movements: resulting in: - Immobile face, with infrequent blinking (Mask Face). - Monotonus Speech. - Loss of swinging of the arms during walking. 5- Postural Instability not caused by primary visual, vestibular, cerebellar, or proprioceptive dysfunction. 6- Other features of PD: Diminished sense of smell (80% of PD patients). - Constipation is common. Sleep disorders: Restless legs syndrome. Dementia: Occurs in 20-40% of patients with idiopathic PD by 10-15 y. Dopaminergic medication may compound the problem. 5 EXTRAPYRAMIDAL DISEASES 6  EXTRAPYRAMIDAL DISEASES Investigations: No diagnostic test for PD. Diagnosis is made on clinical grounds. Management of PD: I. Medical The manifestations of Parkinsonism are due to an imbalance between the levels of acetylcholine (Ach) & dopamine in the basal ganglia & SN. Reduction of dopamine & relative increase in Ach levels are found in all cases of Parkinsonism, whatever the cause. Therefore medical treatment aims to restore the balance by decreasing acetylcholine or elevating dopamine levels. 1- Levodopa (LD) Dopamine Precursor: The most effective & widely used treatment option for the motor features of PD is LD (combined with Carbi-Dopa to inhibit the extracerebral decarboxylation of L- dopa). Levo-Dopa+Carbi-Dopa (Sinemet): Start with one tab daily & increase the dose by ½ tab. Motor complications develop in 50% of all PD patients after 6 years of levodopa therapy (Honeymoon Period). 2- Dopamine Agonists (DA): DA has a role as an alternative to levodopa as monotherapy, particularly in younger patients, to delay the use of levodopa & its long-term motor complications Used as a monotherapy in early disease & as adjuncts to LD in more advanced disease with a consequent lowering of LD dosage. 7 Ropinirole Pramipexole.  EXTRAPYRAMIDAL DISEASES 3- Anticholinergic Agents: Limited role & should only be prescribed in young patients with severe tremor & dystonia. Trihexyphenidyl & orphenadrine or Benztropine. Side effects: a major drawback especially in elderly patients—confusion, cognitive impairment, nausea, dry mouth, precipitation of closed-angle glaucoma, & urinary retention. 4- Amantadine (Antiviral): Previously used in early PD to delay the use of levodopa. With the advent of DA, used now in the management of drug-related dyskinesias. Side effects: confusion, hallucinations, insomnia (give second dose at midday). 5- MonoAmine Oxidase B (MAO-B) Inhibitors: Selegiline & Rasagiline. Used as adjunct therapy to levodopa. 6- COMT Inhibitors: Increase the amount of levodopa reaching CNS. Useful for end-of-dose deteriorations. Entacapone or Opicapone with each dose of levodopa. 8  EXTRAPYRAMIDAL DISEASES Honeymoon Period: It is the first stage of PD which lasting about 6 years, where patients live practically a normal life. It is also the stage where treatment is most effective. II. Surgery/Other Procedures: Surgical treatment of PD may dramatically improve motor symptoms & reduce side effects of dopaminergic therapies by allowing significant reductions and/or elimination of those medications. Best in those whose motor symptoms predominate. 1- Deep Brain Stimulation (DBS) of the thalamic, subthalamic nucleus or globus pallidus is an effective treatment to treat most motor symptoms. Candidates for DBS are those with a meaningful improvement with LD but are unable to sustain the response through the day. It became the surgical procedure of choice for PD for the following reasons: It doesn't involve destruction of brain tissue. It is reversible. It can be adjusted as the disease progresses or adverse events occur. Bilateral procedures can be performed without increase in adverse events. 2- Intestinal Infusion of LD (Duodopa®) using an external pump to better maintain LD benefit through the day & reduce dyskinesias. 3- Thalamotomy & Pallidotomy. 9  EXTRAPYRAMIDAL DISEASES CHOREA Definition: involuntary, static, irregular, dysrhythmic, sudden, jerky, pseudopurposive movements that have an unpredictable, flowing pattern of any part of the body, including the face, trunk and/or limbs. - It is due to a lesion in the caudate nucleus. Causes: 1) Inherited disorders: - Huntington disease. - Benign hereditary chorea. - Wilson disease. 2) Immune mediated chorea - Sydenham chorea - Pregnancy i.e. chorea gravidarum (typically resolves following delivery). - SLE - Paraneoplastic 3) Drug-induced chorea: - Anti-Parkinsonian drugs (L-Dopa). - Dopamine antagonist drugs, e.g. phenothiazines. - Oral contraceptive pills. - Amphetamines, cocaine. - Phenytoin. 4) Metabolic: - hyper- & hypoglycaemia. – hyperthyroidism. - hypocalcaemia. 5) Hemichorea: - Stroke. - Tumor. - Vascular malformation. 10  EXTRAPYRAMIDAL DISEASES RHEUMATIC CHOREA (SYDENHAM'S CHOREA) It is one of the major criteria of rheumatic fever. It is associated with other rheumatic manifestations in about 10% of cases but never with rheumatic arthritis. It's now less common in the antibiotic era. Age: 5-15 years. - Sex: females > males. Aetiology: a result of an autoimmune response that occurs following infection by group-A β-hemolytic streptococci. Molecular mimicry to streptococcal antigens leading to an autoantibody production against cells in the corpus striatum (putamen & caudate) of the basal ganglia. Clinical picture: Choreic Movements: Affecting the tongue, facial, trunk & extremities muscles, being more proximal than distal e.g.: When the patient is asked to keep his tongue protruded & unsupported by his teeth, he is unable to do so & quickly retracts it. Grimacing, jerking of the shoulders, shaking of the hands & feet. The movements increase with emotional stress & disappear during sleep. 11  EXTRAPYRAMIDAL DISEASES Hypotonia: When the patient stretches his arms there is flexion at the wrist & overextension at the metacarpophalangeal & interphalangeal joints with fanning of the fingers giving the Boat Shaped or Scaphoid-Shaped Hand. Emotional Instability: As sudden laughter or crying is observed in most cases. Treatment of rheumatic chorea: Complete rest in bed. Acetyl salicylic acid 6-8 gm daily. Dopamine-Receptor Antagonists - Antipsychotic Medications: Haloperidol PO (Larger doses produce extrapyramidal side effects rapidly). Adverse effects: Extrapyramidal side effects which can be prevented by giving anticholinergic drug concurrently. e.g. benztropine. Corticosteroids in cases of: - Rheumatic activity. - Failure of the above treatment. 12 EXTRAPYRAMIDAL DISEASES 13  EXTRAPYRAMIDAL DISEASES DYSTONIA Definition: Involuntary movement characterized by sustained muscle contraction resulting in twisting & repetitive movements or postures those are due to co-contraction of antagonistic muscles. They are associated with hypertonia during the movement & normal tone in between. Dystonia may be: Generalized: Dystonia Muscularum Deformans (Torsion Dystonia) it is a familial disorder which starts in childhood. Partial: 1- Cervical Dystonia (Spasmodic Torticollis or wry neck): The most common focal dystonia. Dystonia of the Sternomastoid leads to turning of the head to the opposite side, specially when the patient is walking; many cases responds to drugs but some may require myotomy. 2- Oromandibular Dystonia: dystonia of the mouth & jaw muscles. 3- Blepharospasm: Constant involuntary prolonged tight eye closure causing functional blindness. 4- Focal Hand Dystonia (Writer's Cramp): there is spasm & pain of the muscles of the hand & forearm on attempting to write. 14  EXTRAPYRAMIDAL DISEASES Treatment: Anticholinergic drugs, if unhelpful, especially in generalized dystonia, consider: tetrabenazine; pimozide; sulpiride. Baclofen, intrathecally by an implanted pump, can be very effective in certain types of dystonia, Local Botulinum Toxin Injection for focal dystonia. It reduces muscle contraction for approximately 3 months (repeat injection every 3 months) without significant complications. Thalamic Deep Brain Stimulation. Reserved for patients with disabling dystonia in whom other treatment modalities failed. Levodopa should be tried in all childhood-onset dystonias (effective in 10% of cases i.e. Dopa-Responsive Dystonia). 15 THANK YOU