ð¥ å
§ç§å°ç§èåç
Mechanistic Deep Dive
Basal Ganglia Circuitry
- Direct pathway: facilitates movement
- Indirect pathway: inhibits unwanted movement
- Hyperkinetic: â indirect (chorea, ballism)
- Hypokinetic: â indirect / â direct (Parkinson)
VMAT-2 Mechanism
- Inhibits vesicular monoamine transporter
- â Dopamine packaging into vesicles
- â Dopaminergic transmission
- For hyperkinetic disorders
Dopa-Responsive Dystonia Pathophysiology
- â BH4 (tetrahydrobiopterin) cofactor
- â Tyrosine hydroxylase activity
- â Dopamine synthesis
- Replaceable with levodopa
Recent Trials & Updates
Valbenazine + Deutetrabenazine for TD
- KINECT-3 + ARM-TD trials
- FDA 2017
- Effective
Focused Ultrasound (FUS) Thalamotomy
- Non-invasive
- FDA 2016 ET
- 2020 PD tremor
- 2021 dyskinesia
- Increasing utilization
DBS Advances
- Directional leads
- Adaptive DBS
- Closed-loop systems
Anti-IgLON5 Syndrome
- Autoimmune
- REM + non-REM sleep disorder + chorea + parkinsonism + bulbar
- IgLON5 antibodies
- Immunotherapy partial response
Hereditary Spastic Paraplegias (HSP)
80 genetic subtypes
- Spastic paraparesis
- Most autosomal dominant
NBIA (Neurodegeneration with Brain Iron Accumulation)
- PKAN, INAD, others
- âEye of the tigerâ on MRI
- Dystonia + parkinsonism + cognitive
- Mostly children/young adults
High-Yield Specialist Points
Wilson Disease + Movement
- Tremor + dystonia + parkinsonism + dysarthria + psychiatric
- KF rings
- Low ceruloplasmin, high urine copper
- Treat with chelators or zinc
Functional (Psychogenic) Movement Disorders
- Inconsistent
- Variable
- Distractible
- Suggestibility
- Often female, young
- CBT + physical therapy
Stereotypies
- Repetitive, purposeless
- Autism, intellectual disability
- Often comforting
Hemifacial Spasm
- Unilateral facial twitching
- Vascular compression CN VII often
- BTX
- Microvascular decompression
Myoclonus-Dystonia (DYT11)
- ε-Sarcoglycan
- Alcohol-responsive
Paroxysmal Dyskinesias
- PKD (kinesigenic): triggered by movement; brief; carbamazepine
- PNKD (non-kinesigenic): unprovoked; longer; alcohol, caffeine triggers
- PED (exercise-induced)
Cervical Dystonia BTX Protocol
- Multiple muscles target
- Sternocleidomastoid, splenius, trapezius, etc.
- Repeat q3-4 months
- Onset 1-2 weeks, peak 4-6 weeks
Spasticity vs Dystonia
- Spasticity: velocity-dependent â tone, UMN syndrome
- Dystonia: sustained contraction, abnormal posture, often action-induced
Apraxia
- Loss of ability to perform learned motor act
- Despite intact motor/sensory/coordination
- Different from movement disorder
- Cortical (parietal, frontal)
Pearls
- Tremor: rest (PD), postural (ET), kinetic (cerebellar)
- ET: propranolol/primidone, DBS, FUS
- Dystonia focal: BTX first-line
- DRD: levodopa trial always
- HD: AD, CAG, chorea + cognitive + psychiatric; tetrabenazine
- Sydenham: post-strep
- Tourette: motor + vocal tics; CBIT
- RLS: iron + α2Ύ ligands first-line now
- Tardive dyskinesia: valbenazine, deutetrabenazine
- Wilson: always consider in young with movement
- Myoclonus: cortical (epilepsy), post-anoxic, asterixis (metabolic)