wiki

Literature Review

Comorbidity

• Chiari has been associated with autism and connective tissue disorders (if Marfan-like features are common in CTD, we should look at things like height, weight, etc).
• Ehler’s Danlos
  • If Ehler’s Danlos –> more reactive Autonomic Nervous system, can we extract physiological data from BOLD signal, and see if there is a significant difference between Chiari / normal? We would want to look at the rate of change / reactivity.
• Ester and Chen (date) estimate that 12% of children with Chiari I also have seizures or cognitive symptoms
• Craniostenosis (familial cases)
• Found relation between Chiari I and agenesis of corpus callosum (Brill 1997)
• Myleodysplasia (Type II) (Elster 1991)

Hypermobility

• Associated with sub-clinical levels of hypermobility (meaning not hypermobility syndrome) caused by mutations of collagen types. Brighten Criteria are used to diagnose.
  • decompression surgery (Chiari I) is less successful with hypermobility
  • We can look at how the clivus is misplaced over the dens with flexion and distention of the neck to get an idea of how hypermobile someone is. This stress on the spine is called deformative stress.
  • How is this relevant to the spinal cord? Cerebral arteries twist through bone, and hypermobility at c1/c2 means compression and stretching of spinal cord, and complete compression of arteries can occur at 45 to 60 degrees rotation.
    • clivoaxial angle is measure of stability of spine. less than 150 degrees is unstable
  • What happens to a compressed neuron?
    • Aptosis (programmed cell death).
    • Stretching a nerve causes changes in gene expression… it makes neurons more sensitive.
    • Howard 1994 showed that sbnormal stretching leads to sleep apnea.

Subtypes

There are four types, but they are all different.

• Type I is herniation
• Type 2 is ONLY patients with spina bifida, hole in CNS before born, brain doesn’t form properly, cerebellum, medulla, 4th ventricle below foramen magnum.
• Type 3 is herniation of medulla and cerebellum into high cervical meningocele.. caused by same factors as Type II, incomplete closure of neural tube (Argawal 2011)
• Type 4 is birth without cerebellum. (stoke like event in fetus?)

malformation implies something must happen before birth, but there are plenty of examples of people with normal skills that develop tonsil herniation later

Organizations

CSF: chiari and syringomyelgia foundation. Has grants and currently supporting research and mostly creating awareness.

Controversy

• Unknown: What is the cause? It is implied everyone has same problem / cause, and this is not the case! Treatment is based on what is underlying cause, so we need to know this. It’s not a brain problem… results of brain change are because of development of skull and encasemnt of brain (so these are the features that we should look at)
• There is no agreed upon definition of Chiari I
• We don’t know what the cause is
• We don’t understand relationship to fibromyalgia
• We don’t have a good standard for knowing who is a good candidate for surgery
• There is no objective answer for definition of success and failure
• General agreement chiari I, tonsil come down 5mm below foramen magnum. But this is arbitrary…
• There is no agreed upon language for features of images

Causes

4 mechanical things that might cause malformation=====

• skull too small for size of brain (cruzan and feifer’s syndrome)- make head bigger! - 25% of patients with cranio-facial syndromes have chiari because head is too small. None start out with hindbrain syndrome, but develop it at 18+ as brain grows and skull does not.
  • small posterior cranial fossa leads to increased intracranial pressure and over time causes aphasement (rounding off of cranial bone) (Dennis Fitzgerald MD - talk 2010 at csfinfo.org)
• Patients with spontaneous intercranial hypertension (eruption of little cysts spinal cord) will develop because pressure in spine is low, and water sucked out of head, cerebellum sucked into spine. Can get contrast enhanced scans to see “patterns” of someone who has ruptrued cysts, have enchancement of dura –negative intracranial pressure. Treatment in this case usually not surgery on cerebellum, sealing leaks in spine
• Benign Intercranial Hypertension (Pseudotumor Cerebri) increased intercranial pressure with no mass in or on brain.

Demographics

• Higher female prevalence? (Elster 1993)
• Generally seen right in infancy or early adulthood

Symptoms

Symptoms present with cough, laugh, exertion, change head position, trauma

• headache
• ear fullness, (80% time), dizziness (40-50% time), tinnitus according to Dr. Fitzgerald csfinfo.org)
• choking (common in <3 years) (Greenlee 2002)
• headache and scoliosis (3-5 years) (Greenlee 2002)
• dragging foot
• difficulty swallowing
• ataxia, truncal ataxia
• nausea
• sleep apnea
• nystagmus
• lower cranial nerve (5 to 12) dysfunction:
  • 5 sensation
  • 6 eye movements
  • 7 facial nerve
  • 8 hearing
  • 9-10 swallowing
  • 11 raise shoulders
  • 12 move tongue
• motor or sensory deficit upper / lower extremities
• abnormal reflexes
• scoliosis
• back pain
• dysphagia / dysarthria
• coughing (lose consciousness)
• brain being draped over spike of bone in front of brainstem (basilar invagination)
• too much pressure in head by looking in eyes (pseudo tumor)
• obesity is prevalent: BMI over 40 –> pressure in right side of heart too high, causing brain to be bigger, brain herniates through and causes chiari, so losing weight corrects in all cases
• 75% patients: hydromyelia often resulting in scoliosis (Brill 1997)
• spacicity / hyperreflexia
• gait disturbance
• bowel / bladder symptoms

Why do these symptoms occur? (Fitzgerald, 2010 csfinfo.org)

• as brain drops, cranial nerves attached tobrain and are stretched
• 8th cranial nerve as leaves cranial cavity and enters inner ear enters bony tunnel, can be pulled down / compressed against tunnel
• direct compression of bstem by tonsils
• vascular eschemia: nerves and inner ear get blood supply from same on as brain, could be vascular eschemia problem
• increased intracranial pressure –> increased intra cochlear pressure

Diagnosis

• Based on extension of cerebellar tonsils below foramen magnum (5mm abnormal) with head in neutral position (set by Aboulezz et. al)
• Phase contrast MR (PCMR) can be used to evaluate flow (Hofkes 1997), as well as computational flow analysis (CFA) (Roldan 2008).
  • Would it be possible to construct a 3D model of the spine / mid-brain to compare features? (see Roldan 2009) - would need to segment 3D geometry, paper used “Geomagic software” from RTP, NC.
  • Could we use DTI to construct flow models (with directions of csf?)

Treatment

Type 1: Cranial Decompression

Features

Structural

• cisterna magna volume
• herniation of tonsils below foramen magnum (at C1/C2 level in Type I, lower in type II) There are gender differences associated with width of foramen magnum: (Manoel 2009) reported that the FM is higher in males (30.3 ± 0.20) than in females (29.4 ± 0.23), but not in length (p < 0.05)
• herniation of other mid-brain (cerebellum, medulla, 4th ventricle)
• small posterior fossa
• hydrocephalus
• enhancement dura: can get contrast enhanced scans to see “patterns” of someone who has ruptrued cysts, a sign of negative intracranial pressure. Treatment in this case usually not surgery on cerebellum, sealing leaks in spine.
• distortion of skull base - spinal cord pushed against bone in front (odontoid)
• fused skull to C1/C2 or fused ribs
• patients greater than 8mm of length of bone spike do worse, less then 8 mm do better with occopital cranial fusion (younger patients do better)
• underlying cause - base of skull is too short?
• odontoid embedded in spinal cord (nausea, sleep apnea, headaches, etc) - meaning head not secure
• short clivus, skull base small, ability for ligaments to fix to skull base is impaired by short clivus
• clivus, bowl that brain lives in, has a back component (takes shape of skull) and genetic component (inner component)
• inflammatory process –> ligaments become thick in front of spine –> chiari
• ligament gets thicker trying to do its job to stabilize unstable skull, but in getting thicker further crowds the space
• tonsilar “pointedness”
• symmetry (both vs. one tonsil herniated)
• “kinking”

Measures of Successful Surgery

• restore cisterna magna - we want to see lake of spinal fluid at base of skull so csf can move with cough / sneeze
• cisterna magna: lump / lake of spinal fluid below and behind cerebellum, there for a reason! NOT there in people with chiari Is. Can we say we have successfully treated someone if they don’t have a cisterna magna? When heart beats, strain, etc. the cisterna magna is a little resovoir of csf that “adjusts” - when brain gets bigger and tries to displace water, in chiari hole is packed with cereballar tonsils and spinal cord, so when brain gets bigger, gets impacted even more.

People

• Brinn Martin - working with group of volunteers, MRI scans to measure brain volume, tight necktie and another MRI, expecting to see herniation of cerebellar tonsil…
• Paolo Bolongnese
• Roger Cula

Resources / Further Research

• http://www.csfinfo.org/node/274
• Need to look up spine flow / pressure modeling with…DTI? (Roldan 2001) used computational flow analysis - making a model from anatomical and simulating flow, validated with PCMR. Can we say something about physiological signal, flow, and BOLD response?
• Neurohydrodynamic Group
• BioDigital: can MRI data be fed into model?

Data

• Stanford RadTF
• Duke University (Allison-Ashley Koch) has a genetics database, and 200+ manually annotated structural feature sets
  • medical records, family history, pre-operation scans, symptoms, disease onset, pregnancy, etc
  • also taking dura and blood samples from surgery (Are gene expressed in blood different from dura?)
  • they want to ID subsets of patients based on morph. and genes, and look at CNVs
• NKI-Rockland Sample
• 11 patients (18m to 5.5 years) with developmental disorder or seizure history (MRI - 1997)
• 17 patients (4M/13F) age 4-43, (Hofkes 2007) University of Wisconsin Hospital
• 18 patients (8M/10F) age 3-79, (Hofmann 2000) T1, Phase-contrast ECG-gated multiphase sequence
• 68 patients (MR Reports 1985 to 1991) (Elster 1992) - Dept. of Radiology Wake Forest University, Browman Gray School of Medicine
• 31 patients from Iowa Pediatric Database (Greenlee 2002)