Ataxia Flashcards
Role of the Basal Ganglia
- Modulating voluntary motor activity
- amplitude and direction of movement, body language, decision to move
Role of the Cerebellum
- 3 areas and their roles?
- proprioception, vestibular info/ balance, fine movement, hand-eye coordination, predicts sensory consequences
Spinocerebellum (anterior lobe + vermis) –> extremity synergy
Cerebrocerebellum (posterior lobe) –> topography, eye movement, speech coordination
Vestibulocerebellum (flocculonodular lobe + vermis) –> trunk control
Vestibulocerebellar Loop
Paraveramal Area –> Fastigial Nucleus –> Vestibular nuclei on both sides and the reticular formation –> Spinal cord and skeletal muscle
Spinocerebellar Loop
- Stabilize trunk –> EGF/ red nuclei/ reticular formation/ vestibular nuclei
- Stabilize extremities –> EGF/thalamus/ contralateral motor cortex/ lateral cst
Cerebrocerebellar Loop
Info from corticopontine tract –> dentate nucleus –> dentatorubrothalamic tract –> output to sc via lateral cst
Results of lesion to:
- Midline cerebellum (vermis)
- Lateral cerebellum
- Flocculonodular node
- Anterior lobe
- Midline –> issues with gait, trunk balance, head postures, nystagmus, fall with eyes open on Romberg
- Lateral –> issues with hand-eye coordination, speech, dysmetria and dysdiadokochinesia
- Flocculonodular –> truncal ataxia, nystagmus, issues with fixation of gaze and smooth pursuit
- Anterior –> gait ataxia
Direct Pathway vs Indirect Pathway
Direct –> stimulation from cortex stimulates the C/P to inhibit GPi which is normally inhibiting the thalamus
- D1 from SN helps with this
Indirect –> stimulation from cortex stimulates the C/P to inhibit GPe via Ach which is normally inhibiting the STh
- now that STh is active it strengthens the inhibition of GPi on the thalamus
- D2 from the thalamus weakens the indirect pathway by inhibting the C/P (why you get extra movements in PD treatment with Levodopa)
*both occur simultaneously
- role is to inhibit competing movements
PD is an extrapyramidal disorder - what does this mean?
- It does not involve UMN/LMN which are involved in GENERATING movement
- Pyramidal symptoms include spasticity, weakness, hyperreflexia
Definition of PD
- Hypokinetic Disorder
- Bradykinesia plus one of: Tremor @ rest, rigidity, akinesia (bradykinesia), or postural instability
- Usually asymmetric at onset
- Bradykinesia –> slow initiation and progressive decrease in speed/ amplitude w repetitive actions (decrement), micrographia
- Will see neurodegeneration of the SN with Lewy Bodies
Defintion of Tremor
- involuntray rhythmic oscillation of a body part often around a joint
- alternating contractions of muscles
Definition of Chorea (+Ballism)
- brief flitting movements, dance-like
- often multiple body parts
- ballism –> flinging movements of proximal limbs
Definition of Dystonia
- sustained or intermittent contractions causing abnormal and repetitive movements and postures
- patterned, tremulous, twisting
- i.e. Cerebral Palsy
Definition of Myoclonus
Examples?
- brief jerks generated from anywhere along the neural axis
- i.e. hiccups!
- hemifacial spasm (facial nerve, could be Bell’s Palsy)
- Asterixis (negative myocolonus due to liver/ renal failure)
- ACUTE post-anoxic (generalized, brainstem, poor prognosis)
- DELAYED post-anoxic (non-progressive, multifocal, cortical, affects gait and speed)
Definition of Tics
Defintion of Tourette’s
- repetitive semi/purposeful movements proceeded by an urge relieved by the action
- supressible, distractable, suggestable
- 2+ motor tics (at least one vocal), 1 year duration, onset before 18
Definition of Ataxia
- incoordination of voluntary movements due to cerebellar dysfunction causing irregular timing/ precision (speech, swallowing, gait, eyes, limbs, etc)
-Oscillopsia (moving environment), issues with dexterity/ sitting unsupported/ walking
What are neuroleptics?
- block dopamine receptors
- used in the treatment of schizophrenia/ psychosis/ BPD
- can induce tremor/ parkinsonism
Tardive Parkinsonism
Tardive Dyskinesia
Tardive Dystonia
Treatment? If you have to use a neuroleptic, which one should you use?
- persistent parkinsonism (NOT PD) after prolonged neuroleptic withdrawal
- Dyskinesia –> choreifrom oromandibular movements, ELDERLY
- Dystonia –> axial dystonia w trunk and neck hyperextension, YOUTH
*dyskinesia and dystonia are often overlapping and caused by chronic neuroleptic exposure (6m)
Tx –> wean off neuroleptic, anticholinergics, tetrabenzine, botox for cervical dystonia, DBS
- clozapine if you must
What are some drugs that can induce parkinsonism/ tremor?
- Antipsychotics –> haloperidol, risperidone, clozapine, metoclopramide
- Tetrabenzine (DA depleter)
- Valproic acid, lithium, amiodarone, L-thyroxine
- Amphetmaines (cocaine)
- Corticosteroids
- Caffeine, nicotine
- SSRIs/ TCAs
- Alcohol and benzo withdrawal
Acute Dystonic Reaction (ADR)
Tx?
- Occurs days after giving a neuroleptic/ increasing the dose/ switching to IV
- Prodrome of restlessness, fixed gaze, followed by torticollis/ laryngospasm (stridor)/ oromandibular dystonia/ oculogyric crisis/ opisthotonus (neck and trunk hyperextension)/ retrocollis
- treat with ABC, benztropine, diphenhydramine, benzodiazepines
Neuroleptic Malignant Syndrome
Tx?
- Encephalopathy, 2. Rigidity, 3. Hyperthermia,
- Dysautonomia
- high risk for patients w Parkinson’s/ Lewy Body Dementia
- NMS-like syndrome can occur in PD patients who abruptly stop levodopa/ DA agonists (DO NOT DO THIS)
- Treat by stopping offending agents (neuroleptics), benzodiazepines
Cause of malignant hypothermia?
Use of succinylcholine or halogenated inhaled anesthetics in a genetically predisposed individual
Serotonin Syndrome
- Tx?
- caused by SSRIs/ opioids
- hyperreflexia, increased tone, tremor, myoclonus
- Tx is same as NMS –> stop offending agents, benzodiazepines
Describe the course of PD
- Costipation/ REM sleep behaviour disorder
- One shoulder stiffness, stooped posture, difficult to turn, dragging one leg
- Bradykinesia/ resting tremor (not everyone!)/ rigidity/ fatigue/ pain
- Dementia/ urinary issues/ orthostatic hypoTN
- Dysphagia/ falls
- Psychosis
*PD more common in males, incidence has increased in higher GDP countries (Canada the most!)
What are protective factors for PD? What are risk factors?
- Exercise
- Smoking, mediterranean diet (whole grains, nuts, legumes, flavonoids, decreased red meat intake), coffee, vitamin D, NSAIDs, higher urate levels
- Pesticides, rural farm work, chlorinated solvents, lead, head injuries, increased dairy
What are supportive signs of PD?
- Clear benefit from dopamine
- On/off fluctuations
- levodopa induced dyskinesias (chorea)
- Olfactory loss (anosmia)
- Cardiac SNS denervation
What are red flags when considering PD? What are exclusion signs?
- wheelchair, dysphonia/phagia, autonomic issues, no progression in 5 years
- stridor and inspiratory sighs
- Falls in 3 years
- pyramidal signs
- symmetric at onset
- cannot look down, restricted to legs for more than 3 years, no response to Levodopa, agraphesthesia, astereognosis, progressive aphasia, normal neuroimaging of DA system
Multiple Systems Atrophy
- progressive, earlier onset than PD
- Must include autonomic failure –> ED/ urinary incontinence, orthostatic hypoTN
- Parkinsonism features
- MSA-P is poorly Levodopa responsive, MSA-C is cerebellar (gait and limb ataxia, dysarthria, stridor)
Dementia with Lewy Bodies
- Dementia, visual hallucinations, REM sleep disorder, parkinsonism
- Severe sensitivity to neuroleptics, falls, syncope, delusions, anxiety and depression, autonomic dysfunction
Progressive Supranuclear Palsy
- Surprised look, cannot look down, axial rigidity (early falls), pseudobulbar palsy (dysarthria/phagia), dementia
- More commin in men 60-70s
Corticobasal Degeneration
- Asymmetric rigidity, bradykinesia, dystonia, alien hand, myocolonus, apraxia, dementia, agraphesthesia/astereognosis
- Often overlaps with PSP
Essential Tremor
- bilateral, postural hand tremor
- often alcohol responsive
What is the leading cause of death in PD? Who deals with this?
- aspiration pneumonia
- speech language pathologists (also deals with swallowing)
Non-motor symptoms of PD
What explains this?
- depression/ anxiety/ apathy/ delusions
- Paresthesias, insomnia, dry eyes, diplopia, weight loss
- Constipation (lewy bodies in gut, decreases absorption of Levodopa)
- Psychosis, dementia
*psychosis is mainly visual hallucinations and delusions
- deposition of alpha-synuclein in different areas of the brain
Resting vs Action tremor
Resting - supported against gravity (including dangling while walking)
- should subside with action, almost exclusive to PD
Action - either postural (maintaining limb against gravity, physiological) or kinetic (which includes intention tremor - at end of goal-directed movement)
- intention tremor is suggestive of cerebellar disease
Physiologic Tremor
- normal phenomenon enhanced by certain conditions, not associated with an underlying condition
- stress, fatigue, drugs, hypoglycemia, hyperthyroid, etc.
- postural, normally upper limbs
- high frequency (8-12) and fine amplitude
Cerebellar Tremor
- Due to underlying cerebellar disease - presents with ataxia
- Includes intention tremor
- Can be caused by MS, posterior stroke, alcoholic degeneration
- Low frequency (3-5)
Essential Tremor
Treatment?
- Common in older, family Hx
- Postural and kinetic, commonly symmetric in the upper extremities
- Starts high frequency and ends up low frequency with higher amplitude
*If it is an isolated head tremor that is NOT essential tremor. That is cervical dystonia.
1st Line –> propranolol (NO if asthma, hypotn, bradycardia) , primidone
2nd Line –> Gabapentin, clonazepam, topiramate
3rd Line –> DBS
Idiopathic cervical and Idiofocal upper extremity dystonia - tx?
Dopa-responsive dystonia
- both see normal brain and C-spine imagery
- head tremor vs interference with writing
- both treat with botox injections
- genetic, childhood onset, lower extremities and worse in the evening
Huntington’s
Imaging signs?
- cause of Chorea
- dementia, psych disturbances
- autosomal dominant, CAG repeats (more severe with more repeats)
- initally affects the indirect pathway more
- see atrophy of caudate head, loss of neurons, reactive astrocytes and microglia, and intranuclear inclusions (ubiquitin) which represents abnormal huntingtin aggregates
What are some causes of Chorea?
- Huntington’s
- Stroke (contralateral to the lesion, normally in the STh)
- Levodopa induced
- Sydenham (autoimmune, delayed onset following group A strep pharyngitis)
- SLE, antiphospholipid syndrome
What causes the motor symptoms of PD?
- loss of dopaminergic projections from the Substantia Nigra Pars Compacta to the striatum
Levodopa
- prodrug of dopamine, coverted by dopa-decarboxylase present in the CNS and PNS
- causes nausea and vomiting in the PNS so taken with Carbidopa (sinemet) to inhibit dopa-decarboxylase
- Most potent treatment but highest risk of motor fluctuations
Dopamine Agonists
- S/E?
- Moderate benefit, less motor fluctuations (but more fatigue, nausea, ortho, hallucinations)
- May cause impulse control disorders (hypersexuality, gambling)
- i.e. Bromocriptine, pramipexole
- also Amantadine –> mild benefit, mostly used for dyskinesias (constipation, ankle edema, livedo reticularis)
MAO-B Inhibitors
- S/E?
- inhibit metabolism of DA by MAO-B
- weak benefit, used to extend duration of levodopa
- i.e Selegiline
- nausea, dizziness, insomnia, maybe serotonin syndrome if on lots of SSRIs
COMT Inhibitors
- S/E?
- inhibit metabolism of DA by COMT
- must be used with levodopa, extends its duration
- i.e Entacapone
- Orange urine
What classifies wearing off? How to fix?
- under 4 hour duration of an adequate does of LD
- increased dose, decrease dose intervals, add MAO-B COMT inhibitors or DA agonists, long acting or continuous dose LD (intestinal gel via PEG-J), DBS
What classifies as delayed kicking in? Why does it happen? How to fix?
- takes over 30 minutes for LD to work, more common in morning dose
- delayed gastric emptying, constipation, poor absorption due to protein
- manage constipation, space 30 minutes from protein, crush/chew, long acting LD, take meds w carbonated drink, MAO-B inhibitor
What is off vs on?
Off –> medication has worn off and symptoms come back
- common in the AM, leg cramps/ toe-curling/ foot inversion
What are the two types of dyskinesia onset with DA drugs? How to fix?
- Peak dose –> onset at peak of anti-PD effects of meds
- Diphasic (DID) –> minutes after dose or several hours later
- use lowest effective LD dose, if its peak dose use smaller more frequent doses, clozapine, amantadine
Freezing of Gait - Tx?
- more frequent when off
- LD intestinal gel, physio, sensory tricks
- acetylcholinesterase inhibitors/ gait aids to prevent falls
How does DBS work? S/E?
- Stimulates the GPi and STh –> Mimics the on state, but does not treat LD unresponsive symptoms
- generally for younger cognitively intact patients
- Stroke, sensory and cognitive disturbances, personality changes
Which atypical neuroleptics can you give to prevent non-motor fluctuations such as psychosis?
Quietapine, clozapine
What is the role of a social worker in PD?
- advance care planning, power of attorney, long term care
- support groups, employment
Scanning dysarthria
- issues with articulation, prosody, volume
- both cerebellar hemispheres involved
Different inabilities to stabilize gaze? Broken saccades?
- square wave jerks (small saccade away and back), ocular flutter (back to back horizontal), opsoclonus (saccadomania)
- hypermetric (overshoot), hypometric (have to catch up), nystagmus
- impaired VOR cancellation (cannot stabilize gaze while spinning)
Causes of ataxia
- Drugs –> alcohol, lithium, metronidazole, tacrolimus, amiodarine
- vitamin B12 and E and thiamine deficiency
- cancer, paraneoplastic (pancerebellar targeting purkinjes)
- infections, ischemia, congenital, etc.
Alcoholic cerebellar degeneration
- direct toxin, causes thiamine deficiencies
- anterior midline (vermis) structures are most affected
- see midline cerebellar atrophy on MRI, as well as increased MCV and AST
SCA and EA-1/2
Autosomal dominant causes of ataxia
Spinocerebllar ataxia –> CAG repeats
Episodic Ataxia 1 –> seconds to minutes of trunk/limb/ ataxia, normal inbetween and not-progressive
Episodic Ataxia 2 –> hours of N/V, vertigo, progressive inbetween and treated with acetazolamide
Autosomal Recessive Causes of Ataxia
Friedrich’s –> GAA repeat, dorsal column loss, atrophy of cervical cord, cardiac issues common
Isolated Vitamin E Deficiency –> Purkinje cells are sensitive, cord atrophy (like Friedrich’s)
Abetalipoprotinemia –> decreased lipid absorption leads to decreased vitamins ADEK
Cerebrotendinous Xanthomatosis –> cataracts in youth, spatiscity, distal neuropathy
tx –> chenodeoxycholic acid
Signs of cerebellar vs peripheral nerves vs spinal cord ataxia?
Cerebellar –> walking like drunk
Peripheral nerves –> worsens in the dark, decreased ankle jerks, stocking sensory loss
Spinal –> same as peripheral plus wide gait and weakness
Lewy Bodies
- characteristic of PD
- made of alpha-synuclein which accumulates abnormally in neuronal bodies, dendrites, cortex
Topgraphy of cereblleum
- Lateral –> extremities
- Intermediate –> distal limb
- Midline/ vermis –> proximal limb and trunk
- Flocculonodular –> balance, and vestibulo-ocular reflexes
