Transcript Parkinson*s disease

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.
- - Epidemiologic evidence points to a complex interaction
between genetic vulnerability and environmental factors.
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) 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.
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
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.
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.
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 .
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- Amantidin
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
5- temor not responding to medical treatment
6- dystonia
Contraindication to DBS is dementia.