Movement disorders Flashcards
Basal ganglia
General
Collection/clusters of nuclei (neurons)
1. Make Movements
2. Prevent unwanted movements
GABA
- inhibitory neurotransmitter
Glutamate
-excitatory neurotransmitter
DIRECT PATHWAY
Promotes voluntary movement in targeted muscles (from thought to the actual movement)
INDIRECT PATHWAY
Inhibition of movements in other muscles that do not contribute to overall wanted movement (unwanted/undesired motor activity)
striatum releases GABA to inhibiit globus palladus which then in inhibited and releases less GABA which excited Thalamus and promotes movement.
promotion of movement
??
Dopamine
Excited direct pathway
inhibits indirect pathway
Tic disorders
general
Tics are a neuropsychiatric disease common in children and adolescents
sudden twitches, movements (motor tic), or sounds that people do repeatedly (vocal tic). People who have tics cannot stop their body from doing these things.
defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM) based on type (motor or phonic) and duration of tics (sudden, rapid, nonrhythmic movements).
Motor tics
Simple
Simple: appears in one muscle group (nose twitching, blinking and rolling eyes balls, neck and head spasm, head shaking, head leaning back, lip biting, face grimacing or shoulder struggling)
motor tics
complex
Complex: simultaneously in more than 2 muscle groups (usually appears in motions when one is kicking skipping or jumping as he or she walks, imitating others’ movements, flaring nostrils and sniffing, self hitting and twirling in place)
Vocal tic
simple
Simple: dry cough, chocking sound, throat clearing, making animal noises, sniffling, muttering, saying syllables like, hm, ay, ah , ha
vocal tic
complex
Complex: Palilalia ( repletion of one’s own spoken words or sentences), Echolalia (repletion of words spoken by others), stuttering, coprolalia (saying obscene words or searing).
tic disorders
transient
when the tic symptoms temporarily and repeatedly appears and disappear before the age of 18
Chronic Tic Disorder
when either one of motor or vocal tic repeatedly appears and disappears continuously for more than a year
Complex Tic Disorder
- when vocal and motor tics are combined
Tourette Syndrome
when the symptoms of a complex tic last more than a year
tic disorders
causes
Dopamine system Dysregulation
Genetic Factor
Environmental Factors
Psychological factors
tic disorders
Tx
Medication: antipsychotic drugs (haloperidol, pimozide, risperidone…)
Behavior Therapy: relaxation training, habit reversal, family education
Operative treatment: deep brain stimulation, nerve surgery
Alternative treatments: cranio scaral balance therapy, TMJ balancing etc.
tremors
general
non-intentional rhythmic and oscillatory movements of a body part, which are the result of alternating or irregular synchronous contractions of muscles that have an opposite effect on a joint.
tremors
classifiction
Classification based on:
Distribution: which body part is affected
State dependent: Action (Essential Tremor), Rest (Parkinson’s disease)
Tremor frequency (the numbers of oscillations per second) (measured in Hertz)-
Amplitude (distance of movement)
Fine, course, ??
postural- hold a position against gravity
kinetic-
isometric- muscle contraction against something stationary like squeezing a stress ball.
Postural tremor
— Postural tremor happens when you try to hold a body part still, against the force of gravity. For example, your arms might shake if you hold them out in front of you.
Physiologic Tremor
Most common form of postural tremor
Rarely require medical attention, not usually noticeable
Typically affects the upper limbs and hands
Etiology:
Exaggerated physiological response: anxiety fatigue, fright, strenuous exertion.
Drugs like amphetamines, amiodarone, caffeine, valproate, theophylline, alcohol withdrawal
Metabolic: hypoglycemia, pheochromocytoma, thyrotoxicosis
Toxins: mercury
Postural- action
Essential Tremor:
tends to affect the hands and arms and can affect one side (left or right) more than the other.
Other sites: Head (30-40%), voice (15-20%)
No other neurological signs
No known cause (idiopathic)
Prevalence= about 5% in >65 years (males>females)
Family history in 50% of cases (aka familial tremors)
Age of onset: bimodal 10-20s and 40-60s
Can caused marked physical and psychosocial disability
Amplitude increases and frequency decreases with age
Improves with alcohol
postural - action
postural
Dx
Clinical. Exclude other possible causes of tremor based on any other symptoms
Certain medications or supplements often cause tremor, especially stimulants. Beta agonists, lithium, neuroleptics, thyroid drugs and caffeine
Alcohol withdrawal/benzodiazepine
Consider getting TFTs if the patient has symptoms of hyperthyroidism (moist skin, heat intolerance, tachycardia, tachypnea, menstrual abnormalities, goiter, exophthalmos, etc)
Consider imaging if the patient has other neurological symptoms especially gait abnormalities
EMG tremor analysis
EMG tracing
essential tremor
Tx
Depends on severity
Alcohol:
Many patients consume alcohol for its calming effect and prophylactically too
Alcohol has a central effect-it potentiates GABA activity
Drugs :
Reduce tremor amplitude with no effect on tremor frequency
Large amplitude and slow frequency tremor usually do not respond to pharmacological therapy
Propanolol -beta blocker- most effective drug
Primodine
Benzodiazapines (clonazepam, lorazepam, alprazolam)
Kinetic Tremor
general
This type of tremor happens when you are doing a goal-directed activity, such as writing or drinking from a cup.
“Simple kinetic tremor” remains constant throughout the action.
“Intention tremor” gets worse gradually as you get closer to your target (eg, whatever you are reaching for with your arm)
most associated woth cerebellar disfunction
kinetic tremor
Cerebellar Tremor
Typically associated with lesions or diseases that involved the cerebellum or its outflow pathways
Tremors are on the ipsilateral side of the body ( lesion on same side as tremor)
Can be combined with a postural tremor called a head titubation tremor
Amplitude of tremor increasing on approaching target during goal directed movement:
Finger-to-nose, finger-to-finger, and heel-to-shin testing results in worsening tremor as the extremity approaches the target
No drugs have been shown to reduce cerebellar tremors
from stroke or tumor
Isometric Tremor
general
Isometric tremor — This type of tremor happens when you contract a muscle against an unmoving object, for example, pushing against a wall or making a fist.
Rest tremors
general
Most typically seen in Parkinson’s disease
Tremor-dominant Parkinson’s disease is associated with-
Earlier age of onset
Less cognitive decline
Slower progression than the postural instability and gait difficulty variant
The Parkinson’s Disease resting tremor is due to abnormal synchronicity of basal ganglia and thalamic neuronal activity
rest tremor
Rest tremor in upper limb, fingers and hand:
Pill rolling 5Hz
Usually symmetrical
Abolishes by movement but may reappear in new posture
Leg, tongue, lip and jaw may also be involved
Exacerbation by emotional stress
Response to antiparkinsonian drugs
- cerebellar tremor
- parkinsons
- essential
parkinson’s disease
General
Progressive neurodegenerative condition resulting in disorder of movement, autonomic functioning, and in some instances, cognition.
Affects 1% of all Americans over the age of 60. Incidence increased with age. Average age of onset is 60. Very uncommon under the age of 40
Etiology is unclear, but pathogenesis involves degeneration of dopaminergic neurons in the substania nigra par compacta in the basal ganglia
parkinson’s
Cardinal signs:
TRAP
TRAP: Tremor (resting), Rigidity, Akinesia or bradykinesia, Postural instability
parkinson’s
Neuropathology
characterized by the development of α-synuclein (SNCA) aggregates, which are the main components of the Lewy body formations that gradually spread throughout the brain, and affect dopaminergic and non-dopaminergic neurons, including serotonergic neurons
parkinson’s
Hx
onset is usually asymmetric, eventually spreading to other parts of the body in an unpredictable way. Many patients will report having had restlessness during sleep and /or sleepwalking. Some patients will notice a reduction in smell (hyposmia)
parkinson’s
hyposmia
reduction of smell
common in parkinson’s Hx
parkinson’s
Sx
Symptoms: Resting tremor (pill-rolling tremor), reduction in dexterity (often enough to affect the ADLs), Bradykinesia, masked facies, decreased blinking, sleep disturbances, autonomic dysfunction (constipation, sweating, sexual dysfunction), bradyphrenia, dementia
parkinson’s
PE
Resting tremor, cogwheel rigidity (especially at the wrists). Signs reflective of bradykinesia (decreased speed of repetitive movements, micrographia, masked facies, softer/quieter voice which may also be accompanied by poor articulation), fenestrating gait, orthostatic hypotension
parkinson’s
Dx
Clinical diagnosis, other causes should be excluded. With a typical presentation, lab tests and imagining are not needed
Neuroimaging: CT or MRI is only indicated if the patient is younger than 55 or if the patient has additional symptoms not associated with Parkinson’s.
SPECT Scan (Single Positive Emission Computerized): uses 123 I-ioflupane: presynaptic dopamine transporters , can help distinguish Essential Tremor from Parkinson tremor and may help rule out atypical Parkinson diseases
parkinson’s
criteria for Dx
Two or more of the following symptoms not explained by any other condition
-Resting tremor
-Rigidity
-Bradykinesia
Postural instability is associated with more advanced disease
“Parkinson Plus” Syndrome
Shy-Drager syndrome
Progressive supranuclear palsy
Lewy Body dementia
Normal pressure hydrocephalus:
Wet (incontinence), wobbly, wacky (dementia); get CT, symptoms resolve with Lumbar puncture drainage
DDx for parkinson
Essential Tremor:
tremor only, no other symptoms (remember it improves with alcohol)
Huntington’s disease:
Autosomal dominant. Personality changes, anhedonia (apathy), ballismus and chorea (involuntary movements). Degradation of the caudate
Wilson’s disease:
Psychiatric disturbances, liver failure, KF rings; autosomal recessive
Postencephalitic parkinsonism:
recent encephalitis
Adverse effects of neuroleptics:
Tardive Dyskinesia- difficult not moving
Parkinson
Tx
The gold standard of therapy in Parkinson’s Disease is levodopa/carbidopa
Therapy should be tailored towards the individual patient
Other medical therapies:
Anticholinergics: Benztropine
Amantadine
COMT inhibitors: entacapone, tolcapone
MAO-B inhibitor: selegiline, rasagiline
Parkinson
How do we choose which meds?
If the patient is higher functioning (can manage ADLs) and doesn’t have significant postural instability, dopaminergics can be withheld temporarily and the patient can be started on another agent
For patients under the age of 60 the treatment of choice is an anticholinergic (benstrapine)
For patients over 60 the treatment of choice is amantadine, because the adverse affects of anticholinergics are undesirable in the elderly population.
If the patient is lower functioning (ADLs significantly affected) or patient does not respond satisfactorily to previous therapy, dopaminergics should be started.
Levodopa/carbidopa should be started in all patients at this point
For increase effect, adjunctive therapy with Dopamine agonists may be added pramipexole, ropinirole
parkinsons
The major adverse effects if dopaminergic drugs
The major adverse effects if dopaminergic drugs are dyskinesia (abnormal movements), akathisia (restlessness) , nausea and response fluctuation throughout the day.
parkinsons
COMT for adverse effect management
COMT inhibitors are used to reduce fluctuations and adverse effects. They are not used as stand-alone drugs and they do not help any of the Parkinson symptoms themselves. They help regulate the dopaminergic drug level in the blood.
parkinson
domperidone for managing adverse Rx effects
Nausea can be effectively managed with domperidone
parkinsons
MAO-B
When the patient’s response to dopaminergics begins to decline, MAO-B inhibitors can be successful. These are not first line
parkinson
outpatient management
Regular follow ups
referral to neurology
Screen for depression, other mood disorders; in the event of psychosis, the drugs of choice are atypical antipsychotics –quetiapine (dopamine antagonists)
Exercise and speech therapy can improve their quality of life
Making sure their home has assistive devices as needed
Parkinson’s-Plus Syndromes
Progressive supranuclear palsy
Parkinsonian symptom plus vertical gaze palsy
Tremor may not be as prominent
Parkinson’s-Plus Syndromes
Shy-Drager syndrome
Parkinsonian symptoms plus severe autonomic instability, gait issues, nystagmus
AKA multiple system atrophy
Strong symptoms of autonomic dysfunction especially orthostatic hypotension; UMN symptoms hyperreflexia, primitive reflexes; cerebellar symptoms: nystagmus
Get imaging: atrophy of the brainstem and the cerebellum
parkinson’s plus
Lewy body dementia
Parkinsonian symptoms and prominent dementia coinciding or near the onset of symptoms
huntingtons
general
Autosomal dominant genetic disorder; gross atrophy of the caudate and putamen, as well as loss of selective areas of the cortex
CAG repeat sequence creates a mutant, damaging protein
Clinical severity correlates with extent of brain damage
Average age of onset is between 32 and 38 years. Onset age reduces from generation to generation as the CAG sequence tends to elongate.
Ethics take on a particularly important rolls in Huntington’s disease
huntington
Hx
History: In practice, most patients know they may be carriers since they know they have a Family History. Others may have a family history of family members with “early dementia: or of young family members who “died of dementia:. Family history of multiple suicides.
In the minority of patients who are adopted or who do not know their biological family, abrupt personality/personality change along with movement symptoms in a younger patient should raise suspicions
Huntington
Sx
Movement/ cognitive/ behavioral
Movement symptoms: fidgetiness, ballism/hemiballismus, chorea, Parkinsonian features, rigidity
Cognitive symptoms: behavioral disturbances (anhedonia, apathy, untidiness), short-term memory loss, dementia
Behavioral symptoms: change in affect, mood disorders especially Major depression and Obsessive compulsive disorders, suicide, psychosis
huntington
PE
Most notable, chorea, jerky involuntary movements affecting especially the shoulders, hips, and face. Also called dance-like movements. Hemiballismus is a type of chorea, usually involving violent, involuntary flinging of one arm and/or one leg. Athetosis, abnormal muscle contractions cause involuntary writhing movements. Parkinsonian symptoms (bradykinesia, postural instability), rigidity, akinesia.
huntington
Dx
primarily on clinical grounds, however genetic testing is necessary, and it is the most accurate and confirmatory test
Imaging can be predictive as well: increased bicaudate diameter (indicative of caudate atrophy)
huntington
Tx
Supportive. There is no cure for Huntington’s disease, and the onset cannot be delayed
- Ballismus and Choreathetosis can be treated with long-term benzodiazepines
- Patients with Parkinsonian symptoms may be treated with traditional Parkinson’s drugs
- Major Depressive Disorder should be treated with SSRIs
- Psychotic symptoms should be treated with atypical antipsychotics, preferrable risperidone as it is least likely to contribute to movement symptoms
- PT/OT to maximize functional capacity
- Psychiatry referral
- Genetic counseling particularly if patient is planning on having kids
cerebellar Ataxia
general
Ataxia is the loss of control of body movements: it may affect our trunk, one side of our body , both legs or one limb
Causes of Ataxia include:
Inherited/genetic: autosomal dominant; autosomal recessive; X-linked; associated with a mitochondrial disorder
Acquired: structural/demyelinating; toxic/metabolic; paraneoplastic; infectious/postinfectious; autoimmune
Idiopathic (cause not known): cerebellar form of multiple system atrophy (known as MSA); Idiopathic cerebellar degeneration
Cerebellum: organized in a
somatotopic distribution: trunk controlled more centrally and limbs controlled more laterally.
ataxia
lesions
ipsilateral pathology
Lesions just lateral or including the vermis result in truncal or gait ataxia: wide based gait and appear drunk.
Lesions affecting the cerebellar hemispheres result in problems with voluntary limb movements. This is referred to as appendicular ataxia. Finger-nose testing: problems judging distances (dysmetria). Rapid alternating movements: unable to maintain the rhythm and amplitude of the movements (dysdiadochokinesia). Speech can also be affected with variations of intensity and slurring of words
Lesions of the flocculonodular lobe (vestibulo-cerebellum) result in postural instability and impaired eye movement control (nystagmus)
input to the cerebellum
Peripheral nerve> Dorsal Root Ganglia> spinal Cord>
dorsal Column> spinocerebellar pathway> cerebellum
sensory ataxia
general
Sensory Ataxia is a problem with the Proprioceptive pathways
Limb Ataxia
Proprioception defects
Inability to stand with your eyes closed (Romberg test)
Vibration defects
If there is only an issue affects the Nerve or the Dorsal root ganglia then you will have hyporeflexia
fredrich ataxia
general
ataxia
Dx
The timing of onset is very important:
Hyperacute onset (seconds to minutes)
stroke
Alcohol
Acute (hours to Days)
MS (often unilateral)
Subacute (days to weeks)
Paraneoplastic syndromes
metastases
Progressive multifocal leukoencephalopathy is a rare infection of the brain that is caused by the JC (John Cunningham) virus
Chronic: (Months to years)
Degenerative processes
Genetic /inherited
Alcohol
Ataxia
Dx
Neurological and medical history, including drug and toxin exposures
Family history of neurological problems
Neurological and medical examinations
Blood tests to rule out specific deficiencies and toxins
Urine screen for mercury exposure
Brain imaging: magnetic resonance imaging (MRI) or computed tomography (CT)
Neuroimaging of the spinal cord.
Electrophysiologic testing (electromyography and nerve conduction velocity testing) if there are signs or symptoms of peripheral nerve dysfunction
Ataxia
Medications
Medication typically has minimal impact on slowing ataxia’s progression unless it is caused by nutritional deficiencies. In that case, it responds well to supplements. Examples of treatable ataxias include those due to deficiencies of vitamin E or coenzyme Q10, and episodic ataxia type 2.
Drug therapies are available to reduce leg spasticity and address some cerebellar tremors. Several medications can be used for specific symptoms of spinocerebellar ataxia.
Ataxia
alternative Tx
Other ataxia interventions include physical and occupational therapy, and adaptive devices such as a cane, walker or wheelchair. Patients with ataxia may benefit from regular physical and mental exercise, and eating healthy and sleeping well.
Be aware: Ataxia patients are sometimes at a higher risk of mixing medications, falling or developing aspiration pneumonia.
