BG anatomy and spine mets Flashcards
What are the two major devisions of the basal ganglia?
Corpus Striatum and Amygdaloid nuclear complex
What are the subdivisions of the corpus straitum and their function
somatic motor function
Putamen + globus pallidus = lentiform nucleus
Globus pallidus = GPi, medial + GPe, lateral
Substantia nigra = SN pars reticulata (cell poor region close to crus cerebri) + SN pars compacta (cell rich region with large pigmented cells)
What are the subdivisions of the amygdaloid nuclear complex?
hypothalamus, part of limbic system
Describe the subdivisions of the caudate nucleus and the anatomical relationships
Head - buldes into the lateral wall of anterior horn
Body - along thalamus
Tail - follows curve of inferior horn - enters temporal lobe as roof of temp horn, ends in amygdala
Describe the anatomy between the insular cortex and the internal capsule
insular cortex - extreme capsule - claustrum - external capsule - lentiform nucleus - internal capsule
What separates the putamen, GPe, and GPi ?
separated by “medullary laminae”
“lateral medullary lamina” separates putamen from globus pallidus
“medial medullary lamina” separates GPi and GPe
What neurons are contained within the putamen, GPe and GPi?
contain large cholinergic neurons representing extensions from substantia inominata (aka “Basal Nucleus of Meynert, main cholinergic input to brain)
What is the blood supply to the BG?
Medial lentibulostriate - off A1 - caudate head
Lateral Lenticulostriate - off M1 - lentiform nucleus, internal capsule and caudate (head and body)
Anterior Choroidal - off carotid - basal ganglia (medial globus pallidus, tail of caudate nucleus) + internal capsule (genu, part of posterior limb)
Penetrating branches of P1 - posterior thalamoperforating - supply the thalamus, hypothalamus, subthalamus
What are the input nuclei to the basal ganglia?
Caudate
Putamen
Nucleus Accumbens
What are the output nuclei of the basal ganglia?
GPi
SNR
PPN - pedunculopontine nucleus
some consider also - ventral pallidum
What are the intrinsic nuclei of the basal ganglia?
Subthalamic nucleus (STN)
GPe
SNC
some consider also - ventral tegmental area
What are the two feedback loops within the basal ganglia?
STN to GPe (and back) - disruption results in hemiballismus
Striatum to SNR; SNC to Striatum - Parkinsons = ACh influences striatal neurons projecting to the SNR and thus increases SNR Gabaergic output; whilst SNC dopaminergic neurons inhibit striatal ACh release
What is the neostriatum - and what is its input system
Neostriatum = caudate + putamen
inputs from:
1) Cortex
2) Intralaminar thalamic nuclei (Centromedian-parafascicular nuclear complex CM-PF
3) SN
4) midbrain raphe nuclei
5) portions of lateral amygdala
What are reciprocal connections with the neostriatum?
subdivisions of substantia nigra
What is the paleostriatum?
Globus pallidus
output system of BG - GPi = SNR GPi projects to the thalamus - nigrothalamic fibers with collaterals to: Superior colliculus (tectum) and Midbrain tegmentum (PPN)
What is the functional significance of the corpus striatum?
Modulates motor activity via the thalamic neurons projecting to regions of the frontal cortex (prefrontal, premotor, supplementary motor and motor areas)
What are the 5 striatal afferent pathways - that provide input primarily upon the caudate and putamen?
Corticostriate fibers (most important) Amygdalostriate fibers Thalamostriate fibers Nigrostriatal fivers raphe nuclei fibers
What are the 3 striatal efferents that act primarily via the GPi (largest output - pallidal neurons) and the SNR (GABAergic neurons)
Striatonigral fibers
striatopallidal fibers
nigrothalamic fibers
What are 3 features of the striatal neuronal cytoarchitecture?
1) Spiny neurons - long axons - both receive and project
2) Aspiny neurons - short - intrinsic neurons
3) No lamellar organization - two major compartments - patches and matrix
What are the 4 pallidal afferent fibers?
1) striatopallidal fibers (from caudate / putamen to GPi)
2) subtalamopallidal fibers (to GPe)
3) SNC to GPi
4) serotonergic from ascending 5-HT fiber bundles
What are the 2 most important Pallidal efferents? aka the Pallidofugal fibers?
GPe projects to: subthalamic nucleus, and small amount to substantia nigra
GPi projects to: thalamic nuclei, lateral habenular nucleus, midbrain reticular formation
1) KEY - ansa lenticularis
from lateral GPi
ends in Forel’s field H (prerubral area) to merge with lenticular fasciculus and enter thalamic fasciculus
2) fasciculus lenticularis (key output tract)
from medial GPi
fibres called Forel’s field H2, then merge as described above with ansa lenticularis
What are the 5 other Pallidal efferents? aka the Pallidofugal fibers?
1) thalamic fasciculus
- initially designated as bundle H1 of Forel prior to merging with above
2) pallidothalamic projections
3) pallidohabenular fibres
4) pallidotegmental fibres
5) pallidosubthalamic projections
Where is the subthalamic region?
ventral to thalamus, medial to IC, lateral & caudal to hypothalamus
What are the 4 subthalamic afferents?
Dominant is from GPe
1) pallidosubthalamic projections
2) corticosubthalamic fibres
3) thalamosubthalamic fibres
4) tegmentosubthalamic fibres
What is the primary output of the STN?
GPe via the subthalamic fasciculus
corticostriate projections are topographically organized - what is each area involved with?
Putamen - motor control
Caudate - eye movements and cognitive function
Ventral striatum - limbic
What 2 subcortical loops are important for controlling the motor system?
1) basal ganglia Cortical inputs - all areas Cortical outputs - premotor, motor, prefrontal association Spinal connections - none 2) Cerebellum cortical inputs - sensorimotor cortex cortical outputs - premotor, motor spinal connections - receives direct info (vestibulospinal tracts); direct connection with spinal cord
What aspects of movement does each of the basal ganglia and cerebellum regulate?
Cerebellum - execution of movement
BG - cognitive aspects of motor control i.e. planning
What are the two major pathways through the BG?
Direct - excitatory
Indirect - inhibitory
Outline the Direct pathway
cortex excites striatum - striatum further inhibits GPi/SNR output - thalamus released from GPi/SNR inhibitory output - thalamocortical neurons facilitate movement by their excitatory projection on premotor and supplementary motor areas - you move more!
Outline the indirect pathway
cortex excites striatum - striatum further inhibits GPe - STN released from GPe inhibitory effect - STN further excites GPi/SNR output - further inhibition of thalamus by increased GPi/SNR output - decreased facilitation of movement by thalamocortical neurons = you move less!
Outline the dopaminergic effects of the SNc
1) dopamine increases striatal inhibition of GPi/SNR - ie: excites direct pathway = facilitates movement
2) dopamine decreases striatal inhibition of GPe - ie: inhibits indirect pathway = facilitates movement
What occurs to dopamine levels in parkinson’s disease
parkinson’s has too little dopamine - results in excess GPi/SNR output by both pathways = poverty of movement, i.e. bradykinesia
therefore - kill GPi/SNR inhibitory output on thalamus by pallidotomy =parkinsonism treatment
Describe parkinson’s as a negative distubance
A negative disturbance is one of loss of specific neurons / nuclei:
- SNC no longer dumps as much dopamine into striatum as before
- less dopamine around to inhibit ACh release in striatum
- GABAergic output enhanced by the extra ACH hanging around
-note opposite situation in Huntington’s Chorea: loss of ACh and GABA in striatum favors dopamine (indeed, give a parkinson’s patient too much L-dopa and they develop choreiform movements)
Describe a positive disturbance
do not arise directly from destruction of specific nuclei
- represent the functional capacity of surviving intact structures, i.e. “release phenomena”
i. e. hemiballismus following damage to STN
lesion in one structure removes its control from others basis of functional neurosurgery
Outline three targets for the treatment of parkinson’s and their major indictation
1) Vim (nucleus ventralis intermedius) area of the thalamus - target for tremors (of all etiology)
2) ventroposterolateral pallidotomy - especially with rigidity and bradykinesia, less for tremor
3) Ventralis lateralis thalamotomy - treat tremor and rigidity - esp if tremor is most disabling feature
What are complications that can arise from nearby structures in performing a ventroposterolateral pallidotomy
- optic tract (inferior to GPi) with resulting scotoma in the contralateral lower central visual field (2.5-1%)
- internal capsule (medial to GPi) with hemiparesis
- dysarthria (8%, usually temporary)
- ICH
- speech decline, cognitive impairment more risky with bilateral pallidotomies at one setting
What are the 5 most common spinal mets
1- Breast 2- Lung 3- Prostate 4- GI 5- lymphoma
Discuss 3 pathophysiology mechanisms of spinal metsastsis
1) Seeding the VB via 2 routes:
a) arterial emboli to VB marrow then to ant/post ED space via venous channels
b) retrograde spread thru valveless ED batson’s plexus
2) tissue receptivity to embolic neoplasms - cells multiply within fine network of cancelous bone
3) intrinsic tumor factors - gives a cell line a particular advantage in surviving and growing in medullary space
How does spinal mets usually present?
Pain - -initial symptom in 90-95% -worse at night -persists in recumbency -may be due to pathologic # mets to upper C spine may present with suboccipital headache or post cervical pain
Neuro deficit in 40-80%
sphincter deficit
non-ambulatory (50%)
what is the differential diagnosis for spinal met
o degenerative spinal disorder o meningeal carcinomatosis o infection (osteomyelitis, discitis, abscess) o radiation-induced myelopathy o paraneoplastic syndromes o spinal hematoma
what are x-ray features / CT of spinal mets
o 70 % lytic lesions
o 10 % osteoblastic lesions (prostate Ca, breast Ca)
o VB collapse (dec VB ht, inc interpedicular distance on AP film)
o winking owl sign due to pedicle involvement
o paraspinal soft-tissue shadow
o pathological fracture-dislocation
what are the goals of treating mets to spine
- no treatment has been shown to prolong life.
- goals of treatment:
Pain relief
Preserve/restore neurological function
Preserve/restore spinal stability
what are treatment options
Steroids - 10 then 4 mg q 6h
brace
radiation
surgery
list 3 radiation sensitive tumors
prostate , SCLC, and hematopoietic (lymphoma, myeloma) = “PMLs”
what dose of radiation is commonly applies and with what effect?
- 70-80% show good response to XRT
dose: 20-30 Gy over 5-10 sessions to ports extending one VB above and one below lesion extent - for simple palliation of pain (eg. long-standing complete paraplegia) can use 8 Gy single dose
what are 3 complications of spinal radiation?
o N/V o esophagitis (1-2 weeks) o late-onset myelopathy (rare at these doses)
what are 6 indications for surgery in the setting of spinal mets?
Patient factors:
1. rapidy progressing neuro deficit
2. unknown primary and/or no tissue diagnosis (NB: spinal epidural abscess can occur)
Anatomical factors:
3. unstable spine or fracture-dislocation
4. bone rather than tumor causing deficit via deformity / compression
Contraindications for XRT:
5. failure of XRT or radioresistant primary (esp RCC, melanoma, sarcoma, squamous)
6. recurrence after maximal XRT
what are relative contraindications for surgery?
Patient factors: 1. total paralyis > 24 hrs 2. life expectancy 3 levels) Indications for XRT: 5. very radiosensitive tumours not previously irradiated (lymphoma, myeloma, leukemia, GCT)
what are some prognostic factors for those undergoing spinal surgery for mets?
- extent of pretreatment deficit***
- extent of primary tumour control
- duration of symptoms
- histology of primary
- location of tumour
Describe the trial outline and randomization process of Patchell - 2005 spinal mets study
o upfront Sx (24hrs) + XRT (14days, 30Gy) 50 patients
o XRT (24hrs, 30Gy), crossover to Sx if needed 51 patients
o notes:
♣ steroids all pts got decadron 100mg then 24mg q6h (!)
♣ XRT 30Gy x 10 fractions, 8 cm width, 1 vertebral body above & below length
♣ Sx any approach to aggressively resect tumor bulk, stabilization if needed
What patients were eligible for this trial?
o known primary (tissue Dx required)
o at least ONE sign/symptom
o epidural lesion, surgically approachable
o lesion confined to one area, but could include contiguous spinal segments
o CORD compression (root/cauda did NOT count)
o NOT totally paraplegic (0/5 bilat 3 mo
o age > 18 yo
What patients were not eligible?
very radiosensitive tumors: o lymphoma o leukemia o multiple myeloma o germ-cell tumors o primary spinal tumors
Upfront surgery showed upfront improvement in each of these areas:
o ambulation o continence o good strength o good function o survival (trend only) o also, decreased pain & steroid use
what is the aim of the tomita staging system? and what are its subcomponents?
- to assist with Rx decision making for Pts with Met Spinal Column Tumors
Primary tumor
presence of visceral mets
presence of bone mets
How are points tabulated in the tomita staging system?
Primary tumor:
1 - slow growth (breast thyroid)
2 - moderate growth (kidney uterus)
4 - rapid growth (lung, gastric)
Visceral mets
2 - treatable
4 - untreatable
Bone mets
1 - isolated / solitary
2 - multiple
How does the tabulated prognostic score translate into treatment and surgical goals
2-3 = long-term control = wide or marginal excision 4-5 = middle term control = marginal or intralesional excision 6-7 = short term palliation = palliative surgery 8-10 = terminal care = supportive care
What are the subcomponents of the tokuhashi staging system for spinal mets
Karnofsky extraspinal bone mets vertebral mets visceral mets primary site neurological status
what is the maximum number of points and how is treatment determined based on points?
max = 15
good prognosis = 12-15 points - excisional surgery
intermediate prognosis 9-11 - palliative surgery
What are the elements of the SINS scoring system?
Location (junctional=3, mobile=2, semi-rigid=1, rigid=0) pain relief with recumbancy / pain with loading (yes=3, 1=no, pain free=0) bone lesion (2=lytic, 1=mixed, 0=blastic) alignment (subluxation/translation=4, deformity=2, normal=0) v body collapse (>50%=3, 50% bone involvement=1, none of the above=0) posterolateral involvement (facet, pedicle, CV joint) (bilateral=3, unilateral=1, none=0)
how is the SINS score used in practice?
total score 0-18 helps oncolgists know when to get surgical opinion 0-6 = stable 7-12 = intermediate 13-18 = unstable
