PARALYSIS AGITANS

PARALYSIS AGITANS

(Shaking palsy, Parkinson’s disease, Primary Parkinsonism, Idiopathic Parkinsonism)

AETIOLOGY

The cause of PARALYSIS AGITANS disease is unknown. Genetic factor has beensuspected but definite evidences are lacking. No evidence exists for a viral aetiology. Heredo-familial association has not been confirmed.

PATHOLOGY OF PARALYSIS AGITANS

There is degeneration of cells in the pigmented nucleii of the brain stem particularly in the substantia nigra, locus ceruleus, substantia innominata and some reticular nucleii. Small eosinophilic granular bodies and a distinctive cytoplasmic inclusion body called Lewy body are seen. Strionigral degeneration is also visible. There is loss of Dopamine and melanin. Due to degeneration of dopaminergic nigrostriatal system there is depletion of Dopamine. This leads to an imbalance between Dopamine and Acetyl choline. These two neurotransmitters are normally present in corpus striatum. So during treatment, either the effect of Acetyl choline is to be blocked by anti-cholinergic drugs or Dopamine is to be increased by giving Levodopa which is the precursor of Dopamine.

CLINICAL FEATURE OF PARALYSIS AGITANS

Onset is gradual.

Age; 50 to 60 years.

Sex : Males are slightly more affected

(i) Tremor : This is usually the first sign and is commonly noticed in one hand. To start with it is fine but gradually becomes coarse as the disease advances. It is regular and static. Rate is 2-6 cycles per second (4-7 Hz). This is mostly manifested in the distal parts of the limbs. Tremor remains localised in one hand for a long time and after months or years this spreads to the opposite hand and gradually in the lower limbs. Tremor is also noticed in the tongue, eyelids, lips, around the mouth and lower jaw. In a full blown case when tremor is generalised it seems as if the patient is in a state of rage or agitation for which the disease is called paralysis agitans. This can be checked voluntarily or by altering the position of the limb or by some drugs. This is exaggerated during emotion, excitement or fatigue and disappears during sleep. This is inversely related with rigidity. This tremor simulates pill rolling, cigarette making or drum beating finger movements. There may be postural tremor (8-10 Hz) which is finer, faster and persists with activity.

(ii) Poverty of movement (akinesia or bradykinesia) It follows tremor. Automatic movements are first affected. Thus when the patient walks the swinging of the arms is lost. If the patient slips he does not make necessary movements to preserve his balance. However, it is interesting to note that during emergency sometimes effective voluntary activity may be regained very briefly. Standing, sitting all will be slow. Longer time is required to take food. Speech is slow and monotonous with slurring of consonants and repetition of syllables. This is called monotonous speech. The gait is composed of short shuffling steps which is called festinant or shuffling gait. If the patient is pushed from back the forward movements become rapid and it seems as if the patient is trying to catch his centre of gravity. This is called propulsion. Similarly retropulsion and lateropulsions are also seen. Sometimes patient may fall stiffly like a “log of wood” or a”telegraph pole”. Face looses its expression. There is staring look (serpentine stare) due to less blinking and this is called masked facies or Parkinsonian mask. However, on tapping (twice per second) over the glabella continuous blinking is seen. This is called glabellar tap sign or Myerson’s sign.

(iii) Rigidity: This also follows tremor. This is of the cog wheel type because of associated tremor. Cog wheel rigidity is mostly seen in upper limbs while lead pipe type of rigidity develops mainly in lower limbs. Whole body becomes rigid. There is rigidity of the neck, trunk, upper and lower limbs. As a result of which there may be flexed neck and trunk, flexed and crossed upper limbs, and flexed lower limbs. Thus the patient assumes a stooping forward posture during standing. Rarely a hyper-extended position may be seen. There is difficulty in turning from side to side or change of posture in the bed or to stand up from a sitting posture. Buttoning and combing are practically impossible. Due to presence of rigidity, in the early stage jerks are brisk but gradually they cannot be elicited due to rigidity. Cramp or muscle pain is quite common due to rigidity. Blepharoclonus is present. Hand writing becomes cramped and tends to become progressively smaller (micrographia).

(iv) There is no sensory or sphincteric change and superficial reflexes remain normal. Sometimes palmomental reflex may be present.

(v) Involvement of autonomic nervous system may give rise to seborrhea of the face and scalp, (which is very Common) salivary drooling, a central Horner’s syndrome, dysphagia, orthostatic hypotension, thermal paraesthesia, hypomotility of GI tract, bladder dysfunction, excessive perspiration, etc. Arthralgia and myalgia may also develop. Striatal foot and hammer toe are also seen.

(vi) In advanced cases there may be intellectual deterioration.

STAGES

First stage

Mild Unilateral disease

Second stage

Bilateral discase with early postural changes.

Third stage

Prominent change in the gait and moderate generalized disability.

Fourth stage

Pronounced disability.

Fifth stage

The disease is steadily progressive but sometimes may remain stationary.

DIFFERENTIAL DIAGNOSIS

Artheriosclerotic pseudoparkinsonism

Age of onset is later than in paralysis agitans, rigidity is more marked than tremor, evidences of arteriosclerosis are present, e.g., thick arterial walls, retinal arteriosclerosis, etc. Plantar response is extensor and deep reflexes are brisk. Epilepsy and dementia may be present. Some consider arteriosclerotic parkinsonism as no separate entity but same as paralysis agitans.

Hepatolenticular Degeneration

Age of onset is at adolescence; coarse nodular type of hepatic cirrhosis is present; progressive dementia , loss of emotional control, muscular rigidity are present. Kayser- Fleischer ring is found in both eyes. Urine contains excess copper and amino acids, ceruloplasmin level of blood is low.

Anxiety state

The hands are cold, sweating is present, tremor is fine and not coarse, tachycardia is present, rigidity is absent. Tremor disappears with the disappearance of anxiety.

Thyrotoxicosis

Tremor is fine and manifested in outstretched fingers and protruded tongue; thyroid is enlarged with thrill and systolic murmur over it. Tachycardia, collapsing pulse, exophthalmos, high BMR low cholesterol, high Ta, T4 serum PBI and radioactive iodine uptake are present. TSH level is normal.

Senile tremor

It occurs in aged individuals only and manifested during work. Tremor is fine with high rate.

Functional tremor

This is coarse and irregular and may disappear altogether or diverting the attention of the patient. The body is stiff and jerks are brisk, plantar is flexor, and family history reveals hysteric background.

Disseminated sclerosis

Tremor is cerebellar in type, the disease starts at comparatively younger age, recurrence and relapse are very common, evidences of pyramidal mischief are present, ophthalmoscopic examination shows temporal pallor of the disc, scanning speech is present. Nystagums and ataxia are common.

Benign, Essential or Familial Tremor

The cause is unknown. It may be inherited as an autosomal dominant. It starts at any age and is increased with emotional upsets. Hands are involved but legs are spared. Propranolol 60-200 mg per day or Primidone 50 mg daily and gradually increasing the dose is beneficial. Alprazolam and small amount of Alcohol are also helpful.

Shy Drager Symdrome

In addition to features of Parkinsonism, autonomic imbalance like impotence, loss of sphincteric control, anhydrosis, postural hypotension etc. are present . Widespread neurological signs involving extrapyramidal, pyramidal, cerebellar and lower motor neurone are present.

Creutzfaceldt-Job disease

Here apart from Parkinsonian features, ataxia, dementia, myoclonic fasciculation, pyramidal signs and characteristic EEG findings are seen

TREATMENT

1. Physcial activity should be encouraged.

2. Warmth and passive movements are helpful for rigidity.

3. Drugs: In early stages drugs are not required. Anticholinergic drugs are more useful for combating tremor and rigidity than bradykinesia.

(a) Anticholinergic drugs: They are having common side effects like dry mouth, blurred vision, confusion, palpitation, arrhythmia, palpitation, retention of urine, constipation, agitation, drowsiness, restlessness, mydriasis, accommodation defect and rise of intraocular pressure. These drugs should not be used in preostatic enlargement, intestinal obstruction, narrow angle glaucoma. Small doses should be started and then the dose may be increased till desired effect or side effects appear.

(i) Trihexyphenydyl (Artane) 1-6mg daily. Rigidity. akinesia and oculogyric crisis are improved by this drug.

(ii) Benztropine (Cogentin) 1-3 mg twice daily. Its main effect is on tremor and rigidity.

(iii) Orphenadrine (Disipal) 150-400 daily. Its main effect is on tremor and rigidity.

(iv) Procyclidine (Kemadrin) 7.5 to 30 mg daily, Its main effect is on rigidity.

(v) Biperiden (Akeneton) 2-12 mg daily.

(vi) Chlorphenoxamine (Phenoxene) 150 to 400 mg/ day.

(vii) Cycrimine (Pagitone) 5-20 mg/day.

(b) Amantadine : This is used in mild cases. Dose is 100 mg twice daily. There is overall improvement from all angles. Its mode of action is unclear. Side effects like postural hypotension, urinary retention, psychosis, depression may develop.

(c) Levodopa : This is converted to Dopamine in the body. It improves all the major features of Parkinsonism. Nausea, vomiting, cardiac arrhythmia, orthostatic hypotension are common side effects. Rarely restlessness, confusion, behavioural changes and dyskinesia may develop. Chorea, athetosis, tremor, tics, dystonia and myoclonus may result as a part and parcel of dystonia.

A peculiar complication is “on and off” phenomenon in which abrupt but transient fluctuation in the severity of Parkinsonism may occur unpredictably but particularly during the day.

During “off” period there is bradykinesia and during “on”period dyskinesia will be markedly prominent. Sometimes Levodopa is given with Carbidopa which inhibits the enzyme responsible for breakdown of Levodopa to Dopamine. Intra-cerebral breakdown of Levodopa is diminished.

However, this combination cannot prevent the development of “on and off” phenomenon. In a fixed ratio Carbidopa and Levodopa may also be given by using “Sinemet” in a small dose to start with and gradually increasing the dose depending on the improvement. Levodopa should not be given to patients having psychic disorders or narrow angle glaucoma. It should be used with caution in patients taking Monoamine oxidase A inhibitor, or having active peptic ulcer or Malignant melanoma.

(d) Dopamine Agonist These drugs act on Dopamine receptors. These are used particularly when Levodopa therapy is refractory or is associated with marked “off and on” phenomenon. With a low and fixed dose of Sinemet, Bromocriptine the important member of this group, is used and gradually the dose of Bromocriptine is increased till the desired effect is obtained or side effects develop. To start with the dose is 1.25 mg twice daily and increased by 2.5 mg after every two weeks interval. The usual maintenance dose is 10-30 mg per day. Side effects are nausea, vomiting, anorexia, constipation, postural hypotension, digital vasospasm, cardiac arrhythmias, pulmonary infiltration, nasal congestion, headache, mental disturbance, erythromelalgia, etc. This is contraindicated in patients having peptic ulcer, mental disease, myocardial infarction or peripheral vascular disease. Pergolide is another drug used in the dose of 0,05 mg daily and gradually increasing the dose to 3 mg in divided doses. Side effects are hallucination, confusion, constipation, postural hypotension, nausea, vomiting, giddiness, etc….| PARALYSIS AGITANS |

(e) Selegiline: This is a monoamine oxidase B inhibitor which is sometimes used as an adjunct to Levodopa therapy. This drug prevents the break-down of Dopamine and hence it is useful. The dose is 5 mg with breakfast and 5 mg with lunch. It may increase the side effects of Levodopa. Usual side effects are nausea, vomiting, giddiness, confusion and hallucination.

(f) COMT inhibitors like Tolcapone (100 to 200 mg 8 hourly) and Entacapone (200 mg with each dose of L Dopa) also give beneficial results. Tolcapone may result in hepatotoxicities and diarrhoea.

(g) Atypical antipsychotics Drug induced confusion and psychotic symptoms may be relieved by using oblanzapine, quetiapine resperidone and clozapine. Clozapine is more beneficial and can be started at 6.25 mg at bed time and the dose is to be increased to 25-100mg/day. However, it may rarely give rise to marrow depression.

4. Surgical treatment Destruction of globus pallidus or ventrolateral nucleus of the thalamus by stereotaxic surgical procedure may also be done. Dementia is contraindication to surgery.

GENERAL TREATMENT

This includes good nutritious foods, physiotherapy and speech therapy.

BRAIN STIMULATION

High frequency electrical stimulation of thalamus.  Subthalamic nucleii or globus pallidus is also beneficial. Thalamic stimulation is helpful for rest tremor but subthalamic nuclei or globus pallidus stimulation may be beneficial for relieving many Parkinsonian features.

PARALYSIS AGITANS

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