Neurology Dr:Mahmood Kashmoola
Parkinson’s diseaseParkinson’s disease (PD) is the most common form of a group of progressive neurodegenerative disorders characterized by the clinical features of parkinsonism, including bradykinesia (a paucity and slowness of movement), rest tremor, muscular rigidity, shuffling gait, and flexed posture.
Although defined clinically as a movement disorder but it can be accompanied by a variety of non-motor symptoms, including autonomic, sensory, sleep, cognitive, and psychiatric disturbances.
Nearly all forms of parkinsonism result from a reduction of dopaminergic transmission within the basal ganglia.
EPIDEMIOLOGY
-PD afflicts ~1 million individuals in the United States.
-Its peak age of onset is in the early 60s (range 35–85 years), and the course of the illness ranges between 10 and 25 years.
- PD accounts for ~75% of all cases of parkinsonism; the remaining
cases result from other neurodegenerative disorders, cerebrovascular
disease, and drugs.
-Familial forms of known autosomal dominant and recessive forms of PD comprise ~5% of cases . These are generally characterized by an earlier age of onset (typically <45 years) and a longer course than cases of “sporadic” PD.
- Risk factors include a positive family history, male gender, head injury, exposure to pesticides, consumption of well water, and rural living.
-Factors associated with a reduced incidence of PD include coffee drinking, smoking, use of nonsteroidal anti-inflammatory drugs, and
estrogen replacement in postmenopausal women.
CLINICAL FEATURES
A diagnosis of PD can be made with some confidence in patients who present with at least two of the three cardinal signs:
1-Rest tremor (85% of patients)
2- Rigidity
3- Bradykinesia.
A unilateral and gradual onset of symptoms further supports the diagnosis. Masked facies, decreased eye blinking, stooped posture, and decreased arm swing complete the early picture. The onset may also be heralded by vague feelings of weakness, fatigue, aching, and discomfort.
The Patient may suffer from motor, non- motor , and neuropsychiatric disorders.
A:MOTOR FEATURES
The most disabling motor feature of PD is bradykinesia, which interferes with all aspects of daily living including rising from a chair, walking, turning in bed, and dressing.
Fine motor control is also impaired, as evidenced by decreased manual dexterity and micrographia. Soft speech (hypophonia) and sialorrhea are other troubling manifestations of (bulbar) bradykinesia.
Rest tremor, at a frequency of 4–6 Hz, typically appears unilaterally, first distally, involving the digits and wrist, where it may have a “pill-rolling” character. Tremor usually spreads proximally and occasionally to the ipsilateral leg before appearing on the other side after a year or more. It may appear later in the lips, tongue, and jaw but spares the head and neck.
Rigidity is felt as a uniform resistance to passive movement about a joint throughout the full range of motion, accompanied by a characteristic “plastic” quality to the movement. Brief, regular interruptions of resistance during passive movement, due to subclinical tremor, may give rise to a “cogwheeling” sensation.
Dystonia involving the distal arm or leg may occur early in the disease, unrelated to treatment, especially in younger patients. It can also be provoked by antiparkinsonian drug therapy.
Gait disturbance with shuffling short steps and a tendency to turn en bloc is a prominent feature of PD. Festinating gait, a classic sign of parkinsonism, results from the combination of flexed posture and loss of postural reflexes, which cause the patient to accelerate in an effort to “catch up” with the body’s center of gravity.
Freezing of gait, a feature of more advanced PD, occurs commonly at the onset of locomotion (start hesitation), when attempting to change direction or turn around, and upon entering a crowded room or narrow space such as a doorway.
Abnormalities of balance and posture tend to increase as the disease progresses. Flexion of the head, stooping and tilting of the upper trunk, and a tendency to hold the arm in a flexed posture while walking are common, as are changes in the posture of the fingers, hand, and arm. Postural instability is one of the most disabling features of advanced PD, contributing to falls and injuries and leading to major morbidity and mortality. Patients are also at risk for hip fractures, which are
associated with osteoporosis and vitamin D deficiency .
B:NON-MOTOR FEATURES
Non-motor aspects of PD include depression , anxiety, cognitive impairment, sleep disturbances, sensory abnormalities , pain, loss of smell (anosmia), and disturbances of autonomic function. Some of these nonmotor disturbances may be present long before the onset of motor signs.
The physiologic basis of the non-motor signs and symptoms are explained in part by widespread involvement of brainstem, olfactory, thalamic, and cortical structures.
Sensory symptoms often manifest as Aching pain and discomfort in the extremities can be a prominent presenting symptom or develop when
antiparkinsonian medications are wearing off.
Some patients may develop a subjective shortness of breath in the absence of any underlying cardiorespiratory pathology.
Sleep disorders and impaired daytime alertness are common in PD. Restless legs and rapid eye movement behavioral disorder often precede the onset of motor signs of PD. Vivid dreams and hallucinations related to dopaminomimetic therapy may also contribute to sleep disruption. Finally, sleep apnea and other sleep disturbances can also occur. Autonomic dysfunction can produce diverse manifestations, including orthostatic hypotension, constipation, urinary urgency and frequency, excessive sweating, and seborrhea.
Orthostatic hypotension is present in many patients resulting from impaired vasomotor reflexes, sympathetic denervation of the heart, or as a side effect of dopaminomimetic therapy. This rarely leads to syncope unless the patient has developed true autonomic failure or has an unrelated cardiac problem. Paroxysms of drenching sweats may occur in advanced PD, often related to the wearing off of antiparkinsonian medications.
C:NEUROPSYCHIATRIC SYMPTOMS
Changes in mood, cognition, and behavior are common accompaniments of PD, especially in its later stages, and may be the direct result of PD or its comorbid pathologies [e.g., Alzheimer’s disease (AD), cortical dementia with Lewy bodies (DLB)] or may occur as a side effect of antiparkinsonian or concomitant therapy.
Depression affects approximately one-half of patients with PD and can occur at any phase of the illness. Anxiety disorders in PD can appear in isolation or as an accompaniment of depression or progressive cognitive impairment. Mild or moderate cognitive abnormalities affect many patients with PD. These occur in the later stages of the illness and present as frontal lobe dysfunction. The incidence of significant dementia in PD may be as high as six times that in age-matched controls. Psychotic symptoms affect up to 40% of patients with PD, depending on the age, disease duration, and prevalence.
DIFFERENTIAL DIAGNOSIS
Primary and secondary causes must be considered in the differential diagnosis of parkinsonism including:
1-Essential tremor (ET) is sometimes confused with rest tremor in PD, but the absence of other signs of parkinsonism, the bilaterality, higher frequency (8–10 Hz), and postural dependency of ET help differentiate this from the rest tremor of PD.
2-In individuals younger than 40 years, it is important to rule out Wilson
disease. In younger individuals, Huntington’s disease (HD) sometimes presents with prominent parkinsonian features.
3- Although parkinsonian features are often present in AD, they occur late in the course and are greatly outweighed by cognitive and behavioral disturbances.
4-In DLB the parkinsonian features are compounded by the early appearance of hallucinations and disturbances in arousal and behavior .
5-Parkinsonism may also develop following exposure to certain neurotoxins such as carbon monoxide or manganese and antipsychotic therapy.
Investigations:
1-MRI is useful in selected cases to rule out disorders such as normal pressure hydrocephalus, vascular disease, or mass lesions.
2-Positron emission tomography (PET) is helpful in confirming the diagnosis but cannot reliably separate PD from the most common atypical forms.
3-As yet, genetic screening has little place in general practice.
4- In evaluating individuals with PD, it is also important to rule out treatable conditions that may contribute to the disability, such as B12 deficiency, hypothyroidism, testosterone deficiency, and vitamin D deficiency.
Treatment:
The goals of therapy in PD are to maintain function and quality of life and to avoid drug-induced complications.
Bradykinesia, tremor, rigidity, and abnormal posture respond well to symptomatic therapy early in the course of the illness. In contrast, cognitive symptoms, hypophonia, autonomic dysfunction, and imbalance tend to respond poorly.
Medical Therapy
1- Levodopa/ Carbidopa (sinemet) 25/100 or 25/250 starting small dose half tablet twice daily then icrease the dose over 2 weeks to 1 tablet 3 to 4 times per day .
Side effect of sinemet :
A: dyskinesia , wearing off , on off phenomena
-Dyskinesia means choreiform and dystonic movements that can occur as a peak dose effect or at the beginning or end of the dose .
-Wearing off means deterioration of motor symptoms before next dose .
-On off means motor fluctuations between the anti parkonson doses.
B: Other side effect of sinemet are nausea , vomiting due to stimulation of area postrima in the floor of 4th ventricle which can be treated by donperidon
C: Other are postural hypo tention and neuropsychatric manifestation.
2- Dopamin agonist either ergot or non ergot:
Ergot like pergolide not used now because lead to vulvular heart disease.
Non ergot like: - ropirinol starting 0.25 mg 3 times daily gradual increase to 6 to 12 mg per day .
-Pramipexol sarting 0.125 mg 3 times gragual increase to 1to 6 mg per day.
Side effect of dopamine agonist are narcolepsy, neuropsychatric , leg odema ,postural hypotention, vivid dream , hallucination , peptic ulcer, hyperorality and hypersexuality.
3- Catechol-O-methyl transferase (COMT) inhibitors
Entacapone (peripheral) and tolcapone (peripheral and central
COMT inhibitor) . Tolcapone is generally the more effective of the two, but is only used as a second-line treatment because of a (low) risk of potentially fatal hepatotoxicity, necessitating frequent liver function test monitoring. Both drugs can cause gastrointestinal upset, particularly diarrhoea, and a harmless orange discoloration of the urine.
A combined tablet containing levodopa, carbidopa and entacapone (Stalevo) is available.
4- Anticholinergics like benzhexol 5 mg twice daily and trihexphenidyl also same dose, this group mainly used for tremor .
Side effect glaucoma , urinary retention.
5- Amantidin in dose of 100 mg twice daily it acts by inhibiting NMDA receptor this drug used to decrease tremor , freezing and for dyskinesia Side effect are leg edema, hallucination, livedoreticularis and confusion.
6- MAO B inhibitor like selegiline and rasgline they decrease the progression of parkinson disease. the dose is 5 mg twice daily.
Surgical therapy
Deep Brain Stimulation for globus pallidus interna, subthalamic nucleus and ventrolateral nucleus of thalamus.
Indication of DBS:
1- history > 5 years
2- age less than 60 years
3- dyskinesia
4- motor symptoms responding to medical treatment but deleveped motor fluctuation
5- temor not responding to medical treatment
6- dystonia
Contraindication to DBS is dementia.
Treatment of non motor symptoms :
Depresionquetiapine 25 -50 mg per day at night this drug also used for any neuro psychiatric symptoms
Dementia mimantin 10 mg once daily
Oseoporosis and vit. D diffency vit.D and calicium
Also treatment of constipation by high fiber diet , decrease protein intake,,taking the drugs on empty stomach ,frequent small doses , treatment of postural hypotention by elevation of head bed ,adding salt to diet, small dose of fludricortison or midodrin, treatment of impotence by tadalafil lastly physiotherapy.