Parkinson's diseases

📌Parkinson’s disease

🌷definition : 

Progressive, degenerative disorder affect the substantia nigra & locus cerulus -> lead to depletion of dopamine -> so abnormal balance between Ach & dopamine 

noradrenaline also depleted

🌷Epidemiology

0.2 -1% people age above 60 years 

🌷Etiology 

— idiopathic (the most common, called PD or paralysis agitans)

— secondary (Parkinsonism, Parkinson plus)-> age below 40 : 

🌱stoke (Multiple subcortical)

   *tremor less obvious

   *Ix = MRI (multiple stroke)

   *Rx 

= focus on prevention of new stroke 

=low response to anti-parkinsonian medication 

🌱toxins

*Mg dust

*carbon disulfide 

*severe CO poisoning

*exposure to pesticides or fumes during welding لحام (rare)

🌱Pugilistic Parkinsonism (post-traumatic Parkinsonism)

- Parkinsonism 

- dementia 

- behavior changes 

- psychotic symptoms 

- pyramidal and cerebellar deficits 

- Rx = no satisfactory treatment 

🌱Dugs 

*anti-psychotic (haloperidol, chlorpromazine)

*anti-emetic (metochlopramide, prochlorperazine) 

— Rx = stop the drug

🌷Clinical features 

🌱 TRAP 

1️⃣ T = Tremor 

*types : 

- rest tremor 

- postural tremor 

- re-emergent tremor 

*features of resting tremor : 

- asymmetrical 

- increase by distractions, emotional stress 

- decrease by voluntary activity, sleep

- it ca start as 

    *pill rolling (opposing circular movements of the thumb and index finger) 

     *or flexion–extension of the fingers, hand, or foot;

      *pronation–supination of the forearm. 

- involve 

*finger 

*hand 

*arm 

*jaw & chin 

*ultimately be present in all limbs

2️⃣ R = Rigidity 

- lead pipe = resistant to movement throughout the range of movement 

- cog-wheel = rigidity + tremor

- mask face (ddx depression) 

- decrease blinking 

- monophonia 

- excessive drooling of saliva (rigidity in muscles of swallowing and the face ) 

3️⃣ A = Akinesia or Bradykinesia

- the most disabling symptom

*Features : 

-slowness of initiating movement 

-slowness of sustaining repetitive movement (but no weakness)

- gait 

    *small, shuffling steps  

     *no arm swinging during walking 

      *some unsteadiness on turning 

       * difficulty in stopping) 

- handwriting 

    *Micrographia (small)

    *tremulous

    *hard to read 

- Freezing (temporary inability to move)

4️⃣P = posture 

- flexed 

- instable -> fall -> test by pull test

5️⃣Other motor symptoms 

-There is often mild blepharoclonus (fluttering of the closed eyelids) 

-Their is occasionally blepharospasm (involuntary closure of the eyelids)

-The patient may drool, perhaps because of impairment of swallowing . 

- Myerson sign-> Repetitive tapping (approximately twice per second) over the bridge of the nose produces a sustained blink response

 

🌱Mood disorder 

-depression 

- anxiety 

- apathy 

🌱Fatigue 

🌱cognitive impairment 

- mild cognitive impairment 

- dementia

🌱sleep disorder 

- REM sleep behavior 

- insomnia 

- hypersomnia

- sleep fragmentation 

🌱Anosmia (early symptoms) 

🌱Autonomic dysfunction

- postural hypotension 

- bladder dysfunction (urgency and urge incontinence)

- constipation

🌱Seborrhic dermatitis 

🌱Sensory disturbance or pain

🌷Diagnosis 

 The diagnosis may be difficult to make in mild cases

- Possible diagnosis : if there is one of the following :

 *Asymmetric Bradykinesia

 *Asymmetric resting tremor

 *Asymmetric rigidity

- Probable diagnosis -> any two of the above

- Definite diagnosis -> probable + definite response to medication

🌷DDx 

- depression (may coexist-> so add antidepressants)

- Benign familial tremor (essential tremor)

-  Parkinsonism

- dystonia

- Huntington chorea 

- Wilson disease 

- Creutzfeldt–Jakob disease 

- normal pressure hydrocephalus

🌷Treatment: 

🌱supportive treatment 

- physiotherapy 

- symptomatic treatment

🌱 Drugs 

✅carbidopa/levodopa (Sinemet) 

   *unlike the anticholinergic drugs, is often particularly helpful against hypokinesia

*S/E 

- GIT disturbance

- Postural hypotension 

- dystonia

- dyskinesia 

- psychosis 

After 3-5 years of treatment 1/2 - 1/3 of patient will develop the following secondary to loss capacity to store dopamine: 

- end dose phenomenon 

- on off phenomena

- peak dose dyskinesia 

Rx of this by 

- change the dose interval 

- restrict protein diet 

- or use other formula like 

    *controlled release 

    *extended relase

    *intradudenal pump 

- or add 

    *monoamine oxidase type B inhibitors (entacapone) 

    *dopamine agonist 

contraindication 

- glaucoma

- Psychosis 

- MAO-A

also be used with care in patients with : 

-active peptic ulcers 

- suspected malignant melanomas

✅Anti-cholinergic 

- procyclidine

- Benztropine 

- orphenadrine

- trihexyphenidyl 

 useful for tremor & rigidity 

use with caution in elderly 

S/E 

- Visual blurring 

- urine retention 

- confusion 

- constipation 

- dry mouth 

✅Amantadine

- antiviral 

- action = enhance dopamine release in terminal nerve 

- use in 

   *early disease

   * controlling dyskinesia produced by dopaminergic therapy.

- S/E

  * lividoreticularis

   *peripheral edema 

   *confusion 

   *seizure 

   *restlessness 

   *cardiac arrhythmias 

✅Selegiline 

- MOA-B 

- controversy 

- May slow the progression of disease  & with little symptoms relief 

✅COMT 

- entacapone

- given with Sinemet 

✅ dopamine agonist

- first line in young 

- include : 

* bromocriptine

* cabergoline

* lisuride

*pergolide 

*ropinirole 

*pramipexole 

-S/E 

* fatigue 

*hypersominia 

*nausea

*confusion 

*hallucination 

*postural hypotension 

*peripheral edema 

🌱Surgery 

**If no response to medical treatment 

- stereotactic thalamotomy 

- palliditomy

- tissue implantation (Lewy body pathology sometimes spreads to the transplanted tissue.) 

- deep brain stimulation