Huntingtons Disease
- how do you acquire this?
- age of onset
- characterized by
- MOA
Acquire: autosomal dominant
Age: 40yo
Characterized by: chronic progressive chorea, psychological changes, dementia
MOA:
-brain cells waste away
-Decrease in GABA and GABA receptors in basal ganglia. There is an imbalance of dopamine and Ach that cause disease manifestations.
(GABA and Ach reduced & dopamine normal)
- GABA and Ach are inhibitory NT
- Dopamine is excitatory NT
Huntington disease
- Sx in adult/child
- early psychological manifestations
- other early/late physical signs
Sx Adult:
- chorea affects the limbs and trunk
- dystonia
- rigidity
- postural instability
- myoclonus
- nystagmus
Juvenile Onset: RARE
- bradykinesia
- rigidity
- quicker progression
Psychological manifestations:
- Depression* (lack of initiative, spontaneity, inability to concentrate)
- personality changes*
- Memory Loss
- Impulsive behavior (almost like manic bipolar)
- antisocial behavior
- moodiness
- emotional outburst
Physical signs:
Early: fidgeting, restlessness
Late: chorea, dystonic posturing, progressive rigidity, akinesia, dementia
Huntington Dz
-Diagnostic Studies
Dx:
-MRI - caudate atrophy (caudate: one of the structures that make up the basal ganglia)
- PET: abnormal metabolic changes in the caudate
- Genetic Testing: sensitive and specific
Huntington Dz
- Tx
- SE
Tx: can only treat sx
-downregulate dopaminergic neurotransmission
-suppress chorea (Tetrabenazine; breaks down dopamine & Neuroleptics/antipsychotics; deplete cerebral dopamine)
Depression: Prozac, Zoloft, Aventyl(Nortriptyline; TCA)
Postural rigidity and instability: Klonopin(clonazepam), Depakote (Valproic Acid)
Antipsychotics: Resperdal(Resperidone) & Olanzapine (Zyprexa)
Essential Tremor
- how do you acquire?
- describe the tremor
- where can tremor occur?
- highest incidence at what age?
- what makes the tremor worse?
Acquire: inherited
Describe: affects both sides of the body symmetrically, more prominant with ACTION than rest, frequency of tremor is constant. Amplitude may vary.
Tremor may occur in hands, head, hands and head, or voice if laryngeal muscles affected.
Highest incidence in 60+, but may begin at any age.
Aggravated by:
- stress, sleep deprivation, stimulants
- ETOH may relieve essential tremor
Essential Tremor Tx
Propranolol***
Atenolol- beta blocker of choice for those w/ asthma or bronchospasm
Mysoline (PRimidone)- anticonvulsant
Gabapentin (Neurontin) - anticonvulsant
Parkinsons Dz
- Characterized by?
- age at onset
- pathophysiology
- risk factors
Characterized: TRAP T- resting/posture tremor R- Rigidity A-akinesia (bradykinesia) P- postural instability
Age:
generally dx between 45-65, but can occur at earlier stages.
Pathophys:
- loss of dopamine in the substantia nigra
- defective alpha-synuclein and lewy bodies
- Increase in cholinergic interneuron activity d/t degeneration of dopamine pathways (contributing to tremor)
Risk Factors:
- genetics
- Viral/environmental exposures
- aging
What is the leading cause of neurologic dz in pts over 65?
Parkinsons Dz
Parkinson Dz:
-cardinal manifestations:
Manifestations:
-Tremor; mainly hands and feet, pill rolling, usually unilateral, appears at rest and disappears with movement and sleep
- Rigidity: cog-wheel, ratchet-like movement, resistance to movement
- Akinesia (Bradykinesia); slowness in initiating and performing movements, difficult turning, frozen in place esp. when moving through doorway or preparing to turn.
- Postural Instability: lean forward to maintain center of gravity, shuffling steps w/o arm swing, prone to falls
Parkinsons Dz:
-other sx
Other sx:
- dull facies
- loss of blinking
- drooling
- sweating
- micrographia
- hypophonia
- depression
- ortho hypotension
- constipation
- impotence
- urinary incontinence
- dementia (late stage)
Parkinson Dz:
-Dx
Dx: clinical
- gold standard is neuropathologic exam
- 2 of 3 cardinal manifestations must be present
- other confirmation is autopsy
- …heather says some docs give carbadopa/levodopa to see if pts respond.
Parkinsons Dz:
- Tx of sx
- Tx of complications:
- -Depression
- -Hallucination
- -Ortho Hypotension
- -Sexual disturbance
- -Constipation
- -Freezing/Difficulty initiating
- -akinesia/rigidity
- -dysarthria/hypophonia
Tx:
- Levadopa/Carbidopa
- MOA-B inhibitors
- Dopamine agonists
- COMT inhibitors
- Amantidine
- Ach-blocking agents
- max out on these drugs before moving on to deep brain stimulation
Tx of Complications:
-Depression: SSRI
- Hallucinations: decrease levadopa/dopamine agonists or Zyprexa
- Orthostatic Hypotension: TED hose, slow rising
- Sexual Disturbance: Viagra/Dopamine agonist
- Constipation; stop offending medication, bulking agents, no regalan (dopamine receptor antagonist making their sx worse by blocking dopamine)
- Freezing/DIfficulting initiating: tape doorway, mark floor at turning point
- akinesia/rigidity: exercise and PT
- Dysarthria/hypophonia: Speech Therapy
Is DBS more effective than L-dopa?
No, though DBS is like electrical dopamine, PO Levodopa at highest dosage has better effects than DBS at highest dosage.
Restless Leg Syndrome
- aka
- what is this?
- causes
- Pt description of sensation
aka: wittmaack-Ekboms Syndrome
What: uncontrollable urges to move limbs in order to stop uncomfortable, painful, or odd sensation in the body, most commonly the legs
Cause:
- unknown; something in substantia nigra
- reading, plane ride, movie, napping
- iron deficiency
- may be worse in evening and early in the night
Description:
-uncomfortable, antsy, electrical, creeping, painful, itching, pins and needles
RLS:
-may be associated with?
Associations:
- pregnancy
- obesity
- smoking
- anemia
- iron deficiency
- polyneuropathy
- DM
- varicose veins
- Kidney failure
- Medications
- Foods (diet soda; aspartame. ETOH)
RLS:
-Tx
Correct underlying cause
Take pain relievers: OTC ibuprogen
Baths/massages
warm or cool packs
relaxation techniques (yoga/meditation)
good sleep
avoid caffeine
exercise
Medications for parkinsons:
- Pramipexole (Mirapex)
- Ropinirole (requip)
- Carbidopa/levodopa (Sinemet)
- Lyrica
- Opiods: codeine, oxycodone & acetaminophen (percocet), hydrocodone and acetominophen (Vicodin, lortab)
- Epilepsy Meds: Gabapentin (Neurontin)
