Dr. Mahmood . Kashmoola Neurologist F.I.B.M.S (Neurology)

Parkinson’s disease

Parkinson’s disease (PD) is the most common form of a group of progressive neurodegenerative disorders characterized by the clinical features of parkinsonism, including: Bradykinesia rest tremor, muscular rigidity, shuffling gait, and flexed posture. 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 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 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) , decrease blinking and sialorrhea are other troubling manifestations of (bulbar) bradykinesia .

Rest tremor 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 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 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 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.

Abnormalities of balance and posture 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 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.

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, or anti psychotic treatments

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 (25/100 or 25/250). 2- Dopamin agonist either ergot or non ergot: Ergot like pergolide not used now because lead to vulvular heart disease. Non ergot like: - ropirinol -Pramipexol 3- Catechol-O-methyl transferase (COMT) inhibitors Entacapone (peripheral) and tolcapone (peripheral and central COMT inhibitor) A combined tablet containing levodopa, carbidopa and entacapone (Stalevo) is available. 4- Anticholinergics like benzhexol and trihexphenidyl, this group mainly used for tremor . 5- Amantidine which usful in patient with dyskinesia 6- MAO B inhibitor like selegiline and rasgline they decrease the progression of parkinson disease.

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(wearing off and on off phenomena) 5- temor not responding to medical treatment 6- dystonia Contraindication to DBS is dementia.