Movement and Motor Disorders Flashcards
1
Q
list the movement disorders
A
Essential Tremors
Huntington’s Disease
Parkinson’s
2
Q
define movement disorders & what structre their defect arises from
A
Neurologic conditions with abnormalities in voluntary and involuntary movements in the absence of weakness.
All due to imbalance of activity in the complex basal ganglia circuits
- Defect in basal ganglia!!
3
Q
Hypokinetic movements
A
Akinesia – absence of movement
Bradykinesia - slowness of movement
Rigidity - ↑ tone
4
Q
hyperkinetic movements
A
oTics
oTremor
oDystonia
oAthetosis
oChorea
oBallismus
oMyoclonus
5
Q
compare / contrast functions of direct vs indirect pathway
and damage will result in what type of movement disorder
A
Direct Pathway - Making movements (Glutamate)
- Substantia nigra through dopaminergic neuron to activate direct pathway and inhibit indirect pathway
- Damage = hypokinetic
Indirect Pathway - Suppression of movements (GABA)
- Detour to subthalamic nucleus
- Cholinergic neurons activate indirect and suppress direct pathway
- Damage = hyperkinetic
6
Q
funcions of basal ganglia
A
- Help to control movement
- Help to regulate emotion
- OCD: Caudate; Depression: Nucleus accumbens
•Help to regulate cognitive skills
- Memory for skills and habits: striatum
7
Q
define hyperkinetic movement disorders
A
characterized by involuntary movements unaccompanied by weakness and occurring in isolation or in combination.
8
Q
how to hyperkinetic movements differ from tics
A
they cannot be suppressed by voluntary control
9
Q
list hypokinetic and hyperkinetic movement disorders
A
Hypo - parkinsons
Hyper-
- Essential tremor
- Myoclonus
- Ballismus/
- hemiballismus
- Chorea
- Huntington disease
- Athetosis
- Dystonia
10
Q
Rhythmic oscillation of a body part due to intermittent muscle contractions
A
Tremor
11
Q
Sudden, brief (<100 ms), jerk-like, arrhythmic muscle twitches
A
Myoclonus
12
Q
dance-like non-patterned involuntary movements involving distal or proximal muscle groups
A
Chorea
13
Q
Slow, distal, writhing, involuntary movements with a propensity to affect the arms and hands (a form of dystonia with increased mobility)
A
Athetosis
14
Q
sustained or repeated muscle contractions often associated with twisting movements and abnormal posture
A
Dystonia
15
Q
Brief, repeated, stereotyped muscle contractions that can often be suppressed for a short time
A
tics
16
Q
define parkinsonism
A
generic term used to define a syndrome that manifests as
- Bradykinesia - Slowness of movement
- Rigidity
- And/or tremor
17
Q
parkinsonism like dz
A
Parkinson disease (PD)
Progressive supranuclear palsy (PSP)
Multiple system atrophy (MSA)
Corticobasal degeneration (CBD)
Vascular Parkinsonism (VaP)
18
Q
parkinson dz is caused by?
A
Sporadic/unknown – defect in dopaminergic NT
Damage to DIRECT pathway
Defect in substantia nigra
19
Q
Braak Staging is used in what dz?
explain significance?
A
Parkinson’s starts outside of CNS!!
- Mid stage – bradykinesia, rigidity
- Early stage - Constipation, REM sleep disorder 10-20 yrs before onset of parkinsonian si/sx
20
Q
RF for parkinson
A
- Environmental (ex. rural living, well water, pesticides, herbicides)
- Genetic (ex. LRRK2, Parkin, DJ-1, PINK-1)
- Familial (10-15% of cases)
21
Q
motor si/sx of parkinsons dz
A
(“TRAP”)
[Resting] tremor (“pill rolling”) in hands - characteristic
- (also lips, chin, jaw, legs)
Rigidity (cogwheel, lead pipe)
Akinesia/bradykinesia (90%) -Most disabling symptom
Postural disturbances (stoop posture)
- advanced si/sx
- most common cause of falls
22
Q
nonmotor si/sx of parkinsons
A
- Psychiatric disorders (ex. anxiety/depression)
- Cognitive disorders- dementia
- REM sleep disorders – before motor sx
- Autonomic dysfunction – orthostatic hypotension, constipation
- Sensory dysfunction - Olfactory dysfunction, Pain, dysesthesias
- Fatigue
- Weight loss
23
Q
dx criteria for parkinsosn dz
A
The presence of 2 of 3 parkinsonism features
- Tremor
- Rigidity
- bradykinesia
AND good response to levodopa.
24
Q
imaging for parkinsons dz
A
- PET scan
- SPECT
25
histology of parkinsons d
↓ of pigment in SNc --\> degeneration of dopaminergic neurons
Lewy Body accumulation --\> due to a synuclein
26
tx of parkinsons dz
**Symptomatic**: Levodopa/Carbidopa (Sinemet)
**Dopamine agonists** –
* Pramipexole (Mirapex
* Ropinirole (Requip)
**MAO-B inhibitors**
* Selegiline
* Rasagiline
**Surgical treatment** – Deep Brain Stimulation (DBS)
27
# define essential tremor
etiology?
Rhythmic oscillation of a body part due to intermittent muscle contractions
Unknown – GABAergic dysfunction in cerebellum/cortex
28
Most common movement disorder
essential tremors
29
si/sx of essential tremor
High-frequency, _bilat, symmetric, postural & action tremors_ that predominantly affect the _UE_
* _postural & action tremor_ - hands, head & voice.
* Cannot write properly
The tremor is characteristically
* improved by alcohol
* worsened by stress
30
esstential tremors are chanracteristically
## Footnote
improved by\_\_\_\_
worsened by\_\_\_
improved by alcohol
worsened by stress
31
tx of essential tremors
first line
second line
thirs line
First line – BB & anticonvulsants
* Beta blockers (_Propranolol_) – block peripheral non-cardiac B2 receptors in muscle spindle
* Anticonvulsants (_primidone_) – block Na channel & ↑ GABA in CNS
**Second line** – _BZD_ -\> Inc efficiency of GABA
**all fails** – _Botox or surgical_ therapies targeting the VIM nucleus of the thalamus
32
# define Myoclonus
type types
Brief, rapid, shock-like, jerky movement arrhythmic muscle twitches consisting of single or repetitive muscle discharges.
**positive myoclonus** - active muscle contraction
**negative myoclonus** –inhibition of ongoing muscle activity
* Asterixis – hand tremors with hand extension
33
types of myoclonus and when they occur?
**Physiologic** - Nocturnal (usually on falling asleep)
**Essential** - Occurs in the absence of other abnormality (benign)
**Epileptic** - Demonstrable cortical source
**Secondary to disease process**
* Neurodegenerative eg. Wilson’s disease
* Infectious e.g CJD, Viral encephalitis
* Toxic e.g. penicillin, antidepressants
* Metabolic - anoxic brain damage, hypoglycemia, hepatic failure (asterixis), renal failure, hyponatremia
34
Tx of myoclonus
**Benzos**
**Valproic acid**
**Levetiracetam** – inhibiting presynaptic Ca channel à slows down release of excitatory NT
35
define Ballismus/hemiballismus
Uncontrollable, poorly patterned flinging movement of an entire limb (violent chore)
* More dramatic ballistic movements in the arms & legs.
one side of the body (_Hemiballismus_).
36
causes of Ballismus/hemiballismus
**Ischemic stroke** - in the contralateral subthalamic nucleus
**Non-ketotic hyperglycemi**a – ↑ sugar --\> ↓ GABA
37
tx of Ballismus/hemiballismus
Self-limiting - 6 to 8 weeks.
dopamine blocking/depleting agents
* Haloperidol
* Tetrabenazine
38
define Chorea
“Dance”) is characterized by involuntary, irregular, purposeless, random, non-rhythmic hyperkinesias.
* **Present at rest** - ↑ by activity, tension, emotional stress and self-consciousness.
* Patient may be able to t_emporarily /partially suppress movements._
* **Disappear in sleep.**
39
causes of chorea
**Drugs**: _Excessive dose of L-dopa_, dopamine agonists, OCP, phenytoin
**Inherited disorders** - Huntington disease, Benign hereditary chorea, Wilson disease
**Systemic disease** - Thyrotoxicosis, Polycythemia vera, Toxoplasmosis in AIDS
**Immune mediated** - Post-strep. (Syndenham’s chorea), Lupus, Anti-PL Ab
**Stroke, tumor, vascular malformation**
40
When treat patients for HYPOkinetic disorders with\_\_\_\_\_\_\_ can develop\_\_\_\_\_\_ disorders
When treating pts of hyperkinetic movement disorders w/\_\_\_\_\_\_ can develop\_\_\_\_ like si/sx
When treat patients for **HYPOkinetic** disorders with **Levodopa** can develop HYPERkinetic disorders (excess dopa = choreaform)
When treating pts of **hyperkinetic** movement disorders w/ **antipsychotics** can develop **parkinsonian** like si/sx (**hypokinetic**)
41
pathophys of HD
Huntingtin gene ( INC CAG repeats \>35) – anticipatory phenomenon
Predominantly affects the _striatum_.
_Loss of GABAergic neurons_ in the striatum--\> loss of GABA mediated inhibition on s_ubstantia nigra_ --\> _hyperactivity_ of dopaminergic synapses
42
si/sx of HD
characterized by
* motor (gait disturbances)
* behavioral
* oculomotor
* cognitive dysfunction (dementia)
Athetosis/_chorea_
43
tx of HD
can cause 20 Parkinsonism
* Antipsychotics (ex. Haloperidol)
* Tetrabenazine - dopamine depleting drugs
* Antidepressants - Watch for suicidality
There is no adequate treatment for the cognitive or motor decline
44
pathophys of Athetosis
The overflow is due to the f**ailure of the striatum** to s_uppress the activity of unwanted muscle groups_ ---\> **↑ dopaminergic activity** --\> _inability to sustain any body part in one position_
45
define athetosis
Characterized by an inability to sustain the fingers and toes, tongue, or any other part of the body in one position
* Sequential movement w/out your control
46
pathophys of dystonia
_Loss of inhibition_ at multiple levels --\> ↑excitability of **cortex** --\> _abnormal recruitment of muscles_ not needed for specific action
47
define 2 types of dystonia
**Isolated**
* Focal - most common - cervical dystonia, blepharospasm
* Multifocal
* Segmental (affect two adjoining parts of the body)
**Generalized** : Affects most of the body--\> legs & back.
48
# define dystonia
relieveing / aggrevating factors?
Sustained or intermittent muscles contractions of antagonists mm. -\> abnormal, repetitive movements & posture
* _Worsened_ by voluntary action and associated with overflow muscle activation.
* _Relieved_ by relaxation, sensory tricks (Geste antagoniste)
49
tx of dystonia
**Levodopa** tried in _all cases of childhood-onset_ dystonia to test for DRD.
**Anticholinergics** (trihexyphenidyl)
**muscle relaxers** (diazepam)
**GABAB receptor agonist** (Baclofen)
**Botulinum toxin injection** – Most successful for blepharospasm, cervical and task specific dystonias.
**DBS** of the pallidum can provide dramatic benefits for some.
50
identify anatomical regions in the brain affected by these disorders
## Footnote
**Parkinsonism**
**Chronic chorea**
**Athetosis/dystonia**
**Hemiballismus**
**Myoclonus**
**Tremors**
**Parkinsonism** Substantia nigra
**Chronic chorea** [Neo]striatum – caudate nucleus/Putamen
**Athetosis/dystonia** Putamen or thalamus
**Hemiballismus** Subthalamic nucleus
**Myoclonus** Cerebellar cortex/thalamus
**Tremors** Variable - Cerebellum/Brain stem/Frontal lobes/Thalamus
51
list motor disorders
Tourette’s Syndrome
Guillain-Barré Syndrome
Cerebral Palsy
Multiple Sclerosis
52
define pyramidal and extrapyrmidal tracts and their functions
**Pyramidal tracts** - corticobulbar & corticospinal tracts
* Aggregations of efferent nerve fibers from the upper motor neurons that travel from the _cerebral cortex_ and terminate either
* brainstem _corticobulbar_ -- H&N- go through the medullary pyramid
* or spinal cord _corticospinal_
* _control of motor functions_ of the body.
* Most common site of CVA
**Extrapyramidal tracts** --- tracts within the spinal cord involved in _involuntary movement_ but not part of the pyramidal tracts.
* _Subcortical region_
* _functions_ - control of posture & muscle tone
53
cc motor disorders
## Footnote
Corticospinal:
Corticobulbar:
Extrapyramidal:
**Corticospinal**: Muscle weakness, hypertonia, hyperreflexia, clonus, +ve Babinski’s sign.
* Upper motor neuron lesion
* “pyramidal signs”
**Corticobulbar**: Depends on the nerve affected.
* Hypoglossal - Occur on opposite side of affected lesion
**Extrapyramidal**: Dyskinesias (involuntary movements)
54
si/sx of Upper motor neuron lesion
Corticospinal
* Muscle weakness
* hypertonia
* hyperreflexia
* clonus
* + Babinski’s sign.
55
pathophys of MG
**autoantibodies directed against Ach receptors (AchR)**--\> ↓ available AChRs at the postsynaptic muscle membrane.
* ACh produces small end-plate potentials --\> fail to trigger muscle AP --\> weakness of muscle contraction.
The amount of ACh released per impulse normally declines on repeated activity (_presynaptic rundown)._
56
MG is due to autoantibodies against what 2 antibodies?
functions of these?
**Anti-AchR Abs(85%)**
* ↑Turnover of AChRs
* Damage to the PS muscle membrane
* Blockade of the active site of the AChR
**Anti-muscle-specific kinase Abs (MuSK)** - ↓AchR
57
si/sx of MG
weakness & fatigability **W/O loss of reflexes** or impairment of sensation)
58
describe course of the si/sx of MG
Weakness & fatigability of skeletal muscles that worsens with exertion
* As day goes on gets WORSE
**Early MG** - Cranial muscles (lids & EOM),
* Diplopia, ptosis, facial weakness (“snarling” smile), weakness in chewing, nasal timbre speech, difficulty in swallowingà regurgitation / aspiration
**Weakness becomes generalized affecting limb muscles (proximal, asymmetric)**
59
dx of ocular MG
Restricted EOM weakness for 3 years
60
dx of MG
**Antibodies to AChR, MuSK, or Ipr4 (diagnostic!!)**
* (-) does not r/o
**Electrodiagnostic testing**
* Repetitive nerve stimulation -- ↓ \>10–15% in the amplitude.
**Edrophonium test (acetylcholinesterase inhib)**
* Edrophonium (2 mg + 8 mg IV) --\> improvement in muscle strength.
**+/- CT/MRI:** For ocular or cranial MG:
* exclude IC lesions
61
tx of MG
**FIRST LINE**- acetyl inhib + Steroids
Acetyl cholinesterase inhibitor (2-4 hrs)
* Pyridostigmine
* Neostigmine
Immunosuppressants
* Systemic steroids
* Cyclosporine A
* Azathioprine
* Mycophenolate mofetil
* Cyclophosphamide – toxic metabolite
**Surgical thymectomy**
62
# define MG crisis
Tx
Infections or systemic disorders --\> weakness --\> Resp. failure--\> “crisis”
Plasmapheresis
IV Immunoglobulin
63
Concurrent Thymus disorder is assoc w/ what dz?
pathophys??
MG
Thymic disorders (ex. thymoma, thymic hyperplasia-\> dysregulation of thymus --\> production of autoreactive T-cells\> T-cell mediated destruction of Ach receptors
64
define motor and sensory tics
A tic is a brief, rapid, recurrent, and seemingly purposeless stereotyped motor contraction.
**sensory** tics, composed of unpleasant focal sensations in the face, head, or neck. (mild- severe
65
types of motor tics
**Simple,** individual muscle group (blinking, twitching of the nose, jerking of the neck),
**Complex**, with coordinated involvement of multiple muscle groups (jumping, sniffing, head banging, and echopraxia).
**Phonic tics** - simple (grunting) or complex (echolalia, palilalia and coprolalia)
66
tourettes syndrome is assoc w/ what other dzs?
assoc with anxiety, depression, ADHD, and OCD
67
pathophys of toureettes
Not known; changes in dopamine neurotransmission, opioids, and second-messenger systems have been proposed.
68
si/sx of tourettes
characterized by multiple motor tics & vocalizations (phonic tics).
* characteristically can voluntarily suppress tics for short periods of time
* but then experience an irresistible urge to express them.
69
dx of tourettes
Diagnosed when a person exhibits both multiple motor and one or more vocal tics over the period of a year.
70
tx of tourettes
**Mild dz** - Education/counseling
**Habit reversal therapy**
**α2-adrenergic agonists**: clonidine, guanfacine
**Neuroleptics**
* _Atypical neuroleptics_ (risperidone, olanzapine, ziprasidone)
* _Classical neuroleptics_ (haloperidol, fluphenazine, pimozide, or tiapride)
**Botox**- focal tics or DBS
71
complication w/ tx of tourettes
Medication side effects (ex. tardive dyskinesia w/ classical Neuroleptics )
* haloperidol, fluphenazine, pimozide, or tiapride)
72
list classical and atypical antipsychotics
**Atypical neuroleptics**
* risperidone
* olanzapine
* ziprasidone
**Classical neuroleptics**
* haloperidol
* fluphenazine
* pimozide
* tiapride
73
define and list causes of GBS
Acute-onset immune-mediated demyelinating neuropathy. (more males)
acute, frequently severe, & fulminant polyradiculopathy that is autoimmune in nature
* Antecedent Events: 1-3 wks after URI or GI
* Campylobacter jejuni – most common cause in US
* Mycoplasma pneumoniae
* Recent immunizations
74
pathophys of GBS
Demyelination --\> conduction block --\> flaccid paralysis & sensory disturbance --\> rapid recovery w/ remyelination if axons remain intact
_Severe cases_ : Axonal injury--\> slower rate of recovery --\> ↑ disability
75
types of GBS
Acute inflammatory demyelinating polyneuropathy (AIDP) \*\*
Acute motor axonal neuropathy (AMAN)
Acute motor sensory axonal neuropathy (AMSAN)
76
si/sx of GBS
Rapidly evolving _ascending paralysis_ (“**rubbery legs”)** (\<4 wks other body parts)
* **Hyporeflexia/areflexia**
**Facial diparesis** (~70% of pts),
* pain in the neck, shoulder, back, or diffusely over the spine
* Tingling dysthenias
**Autonomic involvement (later)** –
* fluctuation in BP
* postural hypotension,
* cardiac dysrhythmias.
77
dx GBS
recognizing the pattern of rapidly evolving paralysis with **areflexia, absence of fever**
**CSF** – _albumin cytologic disassociation_
* CSF protein level (1-10 g/L) w/o ↑WBC --\> _pleocytosis_ (after 48 hrs)
**Electrodiagnostic testing**- Edx slowing of conduction velocity, conduction block, and temporal dispersion
* _Myelin sheath injury_ --\> delayed conduction
* _Axonal injury_ -- ↓ amplitude
78
compare / contrast MG vs GBS
reflexes?
sensation?
**MG** - weakness & fatigability **W/O loss of reflexes** or impairment of sensation)
**GBS** - recognizing the pattern of rapidly evolving paralysis with **areflexia**, absence of fever
79
tx of GBS
Treatment should be initiated _ASAP_
* **High dose IVIF or plasmapheresis**
* NO glucocorticoids !!!*
80
causes of Cerebral palsy
**Antenatal (80%)**
* Cerebral dysgenesis
* Congenital infection (TORCH)
* Substance abuse/prematurity
**Intrapartum** (10%) -- Birth asphyxia/ trauma (breech)
**Postnatal**
* Intraventricular hemorrhage/ischemia
* Meningitis/encephalitis
* Head trauma
* Hyperbilirubinemia
81
motor types of cerebral palse
location of brain
sx?
**Spastic**: (motor cortex) Most common (~91%)
* _Pyramidal Sx_ (tremors,hyporeflexia hypertonicity, tip toe walking, scissoring gait)
* muscles are _stiffer_ than normal.
**Dyskinetic** (basal ganglia)
* Recurring, uncontrollable & i_nvoluntary movements_, exacerbated during stress
* _fluctuating tone_
**Ataxic** (cerebellum least common)
* Generalized hypotonia w/ _loss of muscle coordination / balance_
* Wide based gait
* _↓ proprioception_
82
tx of cerebral palse
**Botox, Baclofen** - control muscle spasms and seizures
**Glycopyrrolate** - control drooling
**Pamidronate** -may help with osteoporosis
83
define MS
Autoimmune (T-cell mediated destruction of myelin sheath proteins) - characterized by chronic inflammation, demyelination, gliosis, & neuronal loss
_Demyelination_ - pathological hallmark and evidence of myelin degeneration is found at the earliest time points of tissue injury.
84
list types of MS
**Relapsing Remitting Disease (RMS):** ~85% - progression characterized by relapses of active disease with complete recovering during periods of remission.
**Secondary Progressive Disease (SPMS):** R&R then becomes progressive
**Primary progressive disease (PPMS):** ~15% - symptoms are progressive from the onset NO remission!
85
patho of MS
* BBB problem --\> T-cells get inside CNS & get activated --\>
* T-cell mediated destruction of myelin proteins & cytokine production --\> inflammation
* B-cells produce abs against myelin sheath --\> complement activation & abs mediated phagocytosis
86
RF for MS
* Genetic predisposition
* Vit D deficiency
* EBV exposure in early childhood
* Smoking
87
si/sx of MS
*Sensory, motor &autonomic*
**Sensory symptoms:**
* paresthesia's (e.g., tingling, prickling sensations, “pins and needles,”
* painful burning) and hypesthesia (e.g., reduced sensation, numbness,
* or a “dead” feeling).
**Optic neuritis (ON)** – common early sx
* diminished visual acuity, dimness,
* decreased color perception (desaturation) in the central field
**Weakness of the limbs.** Exercise-induced weakness is a characteristic symptom of MS.
88
dx of MS
At least 2 episodes of Sx that occur at different points in time
**MRI** (focal white matter lesions)
**Lumbar Puncture** – mild pleocytosis and a total protein usually normal.
* Protein \> 100mg/dl is unusual and should be evidence against MS
**Evoked potentials** - detect slow or abnormal conduction in response to visual or auditory stimuli
89
tx of acute attacks of MS
IV Glucocorticoid – methylprednisolone
90
Disease modifying therapies of MS
highly effective
modestly effective
**Highly Effective:**
* _Dimethyl fumarate_ – anti-inflammatory effects
* _Natalizumab_ - preventing lymphocytes from penetrating the BBB and entering the CNS
* _Alemtuzumab_ – lymphocyte (B & T) depletion
**Modestly Effective:**
* _Interferon β_ - ↓MHC Class II, ↓T cell proliferation
91
symptomatic tx of MS
## Footnote
**Spasticity** –
**Optic Neuritis**
**Fatigue** –
**Pain** –
**Tremor** –
**Spasticity** – Baclofen, Cyclobenzaprine
**Optic Neuritis** – Methylprednisolone, Oral Corticosteroids
**Fatigue** – Amantadine, Anti-depressants
**Pain** – Gabapentin, Pregabalin
**Tremor** – Propranolol, Primidone
92
motor disorders are due to defect in ??
movement disorders are due to defect in??
_motor disorders_ are due to defect in- _pyrmidal/ extrapyrimidal tracts_
_movement disorders_ are due to defect in- _basal ganglia_
