MOVEMENTS DISORDERS DISEASES OF EXTRAPYRAMIDAL SYSTEM DISEASES OF BASAL GANGLIA

Parkinson Disease Parkinson disease is an idiopathic, slowly progressive, degenerative disorder characterized by resting tremor, stiffness (rigidity), slow and decreased movement (bradykinesia), and gait and/or postural instability. Parkinson disease (PD) affects about 0.4% of people > 40 yr, 1% of people ≥ 65 yr, and 10% of people≥ 80 yr. The mean age at onset is about 57 yr

Rarely, PD begins during childhood or adolescence (juvenile parkinsonism). Onset between ages 21 and 40 yr is sometimes called early-onset PD

Pathophysiology Synuclein is a neuronal and glial cell protein that can aggregate into insoluble fibrils and form Lewy bodies. The pathologic hallmark of PD is synuclein-filled Lewy bodies in the nigrostriatal system. In PD, pigmented neurons of the substantia nigra, locus ceruleus, and other brain stem dopaminergic cell groups degenerate. Loss of substantia nigra neurons results in depletion of dopamine in the dorsal aspect of the putamen (part of the basal ganglia) and causes many of the motor manifestations of PD

Etiology A genetic predisposition is likely, at least in some cases. About 10% of patients have a family history of PD. Several abnormal genes have been identified. Inheritance is autosomal dominant for some genes and autosomal recessive for others. In genetic forms, age at onset tends to be younger, but the course is typically more benign than that of later-onset,

Symptoms and Signs In most patients, the disease begins insidiously. A resting tremor of one hand is often the first symptom. The tremor is characterized as follows Slow and coarse Maximal at rest, lessening during movement, and absent during sleep Amplitude increased by emotional tension or fatigue

Often involving the wrist and fingers, sometimes involving the thumb moving against the index finger (pill rolling), as when people roll a pill in their hand or handle a small object Usually, the hands or feet are affected first, most often asymmetrically. The jaw and tongue may also be affected, but not the voice. Tremor may become less prominent as the disease progresses

Rigidity develops independently of tremor in many patients Rigidity develops independently of tremor in many patients. When a clinician moves a rigid joint, semirhythmic jerks due to variations in the intensity of the rigidity occur, producing a ratchet-like effect (cogwheel rigidity). Slow movements (bradykinesia) are typical. Movement also becomes decreased in amplitude (hypokinesia) and difficult to initiate (akinesia

Rigidity and hypokinesia may contribute to muscle aches and sensations of fatigue. The face becomes masklike (hypomimic), with an open mouth and reduced blinking. Excessive drooling (sialorrhea) may contribute to disability. Speech becomes hypophonic, with characteristic monotonous, sometimes stuttering dysarthria. Hypokinesia and impaired control of distal muscles cause micrographia (writing in very small letters) and make activities of daily living increasingly difficult. Without warning, voluntary movement, including walking, may suddenly halt (called freezing of gait

Postural instability may develop, resulting in falls, which occur later in PD. Patients have difficulty starting to walk, turning, and stopping. They shuffle, taking short steps, holding their arms flexed to the waist, and swinging their arms little or not at all with each stride. Steps may inadvertently quicken, while stride length progressively shortens; this gait abnormality, called festination, is often a precursor to freezing of gait. A tendency to fall forward (propulsion) or backward (retropulsion) when the center of gravity is displaced

Dementia Sleep disorders are common.

Neurologic symptoms unrelated to parkinsonism commonly develop because synucleinopathy occurs in other areas of the central, peripheral, and autonomic nervous systems. Almost universal sympathetic denervation of the heart, contributing to orthostatic hypotension Esophageal dysmotility, contributing to dysphagia and increased risk of aspiration Lower bowel dysmotility, contributing to constipation Urinary hesitancy and/or urgency, potentially leading to incontinence (common) Anosmia (common) In some patients, some of these symptoms occur before the motor symptoms of PD. Seborrheic dermatitis is also common

Diagnosis Mainly clinical evaluation, based on motor symptom

Treatment Carbidopa/levodopa (mainstay of treatment) Amantadine MAO type B (MAO-B) inhibitors, or, in few patients, anticholinergic drugs Dopamine agonists Catechol O-methyltransferase (COMT) inhibitors, always used with levodopa, particularly when response to levodopa is wearing off Surgery if drugs do not sufficiently control symptoms or have intolerable side effects

Chorea Movements are nonrhythmic, jerky, rapid, and nonsuppressible, primarily in distal muscles or the face. Sometimes abnormal movements are incorporated into semipurposeful acts that mask the involuntary movements. Chorea often occurs with athetosis as choreoathetosis

Huntington disease, hyperthyroidism, hypoparathyroidism, paraneoplastic syndromes, SLE affecting the CNS, other autoimmune disorders, rheumatic fever, tumors or infarcts of the caudate nucleus or putamen Pregnancy, often in women who had rheumatic fever Senile chorea Drugs that can cause chorea (eg, levodopa, phenytoin , cocaine, oral contraceptives Drugs that can cause tardive dyskinesia (eg, antipsychotics

Athetosis (slow chorea) is nonrhythmic, slow, writhing, sinuous movements predominantly in distal muscles, often alternating with postures of the proximal limbs. Huntington disease, encephalitis, hepatic encephalopathy Drugs (eg, cocaine, amphetamines, antipsychotics

Hemiballismusis unilateral rapid, nonrhythmic, nonsuppressible, wildly flinging movement of the proximal arm and/or leg; rarely, such movement occurs bilaterally (ballismus). Hemiballismus is a severe form of chorea

Dystonias Sustained muscle contractions often distort body posture or cause twisting, repetitive movements. Primary (idiopathic) Degenerative or metabolic disorders (eg, Wilson disease, various lipidoses, multiple sclerosis, cerebral palsy, stroke, brain hypoxia) Drugs that block dopamine receptors, most often antipsychotics (eg, phenothiazines, thioxanthenes, butyrophenones) or antiemetics