GI manifestations of neurologic disorders

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GI manifestations of neurologic disorders

• Iyad Issa MD

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OUTLINE

• Multiple neurologic disorders
• HHT
• Dementia
• Stroke
• Feeding
• Aspirin

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The Brain Gut axis

• The GI tract down to the mid-colon is supplied
  with efferent afferent nerve fibers running in
  the vagal splanchnic trunks

CNS
Vagal pathway
Splanchnic pathway
GUT
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The Brain Gut axis

• Afferent neurones discharge in response to
  luminal chemicals, mechanical deformation of
  their terminal fields, humoral factors, cytokines
  and inflamatory mediators endocrine cells and
  mast cells and cells of the immune system that
  may be influenced by lumenal chemicals.

CNS
Vagal Splanchnic pathways
Lumenal chemicals Muscle tension Enteroendocrine
cells Mast cells Cytokines
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The Brain Gut axis

• Efferent neurones in both splanchnic and
  vagal nerve trunks terminate on myenteric nerve
  cell bodies from which intrinsic motor neurones
  influence secretion and motility sympathetic
  efferents may also directly supply blood vessels.

CNS
Vagal pathway
Splanchnic pathway
Humoral factors
Enteric motor neurones
Intrinsic afferent interneurones
Secretion
Motility
Bld flow
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GI symptoms of some neurologic disorders
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Multiple sclerosis
Common problems
Fecal incontinence
Constipation
Impaired ext int anal sphincters
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Intracerebral hemorrhage
No RCTs evaluating GI bleed in setting of
intracerebral hemorrhage
Misra UK, J Neur Sci. 20825, 2003
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A L S

• Progressive muscle atrophy weakness
• Dysphagia will be present in all patients
• Recent studies
• Rapid PEG
• Better quality of life

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Spinal cord injury
INJURY
Late period
Early period
PUD
Stasis
Autonomic dysreflexia
Constipation
Rare diseases
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Spinal cord injury
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Spinal cord injury
Damage to neurones
Loss of gastrocolic reflex
Chronic constipation
Treatment
Exercise
Fluids
Stool softeners
Digital distention
Stimulant laxatives
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Spinal cord injury
Steroid use
1980 --- 1984 107 patients
16 mg / day dexamethazone For spinal cord
compression
GI perforation as frequent as GI bleed More
serious more difficult to Dx Prevention of
constipation may help
Fadul CE, Neurology. 38348, 1988
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Hereditary Hemorrhagic Telengiectasia

• Osler Weber Rendu

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Hereditary Hemorrhagic Telengiectasia

• A grp of autosomal dominant disorders
• 1896???Rendu---Epistaxis telengectasias
• 1909???Hanes---H H T
• Prevalence
• 12500 145000

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Hereditary Hemorrhagic Telengiectasia

• Abnormalities in vascular structures
• --- Telengiectasias are universal
• --- A-V malformations are common

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Hereditary Hemorrhagic Telengiectasia
Diagnosis is based on 3 of the 4 Curacao criteria
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Hereditary Hemorrhagic Telengiectasia
Early in life Most common sx Recurrent epistaxis
Nose (gt95)
Skin (gt80)
Later in life Lips, tongue, palate
GI tract (30)
Lungs (30)
Liver (30)
Brain (10)
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Hereditary Hemorrhagic Telengiectasia
GI bleed 4th-5th decade Telengiectasias Stomach
SB Rx Photocoagulation Estrogen Progesterone
Nose (gt95)
Skin (gt80)

• Hepatic AV malformation
• Presentation
• Congestive heart failure
• Biliary inv (strictures)
• Portal HTN
• Treatment
• Embolization?
• Liver transplant

GI tract (30)
Lungs (30)
Liver (30)

• Pulmn AV malformation
• CV accidents
• Cerebral abscess
• Dyspnea
• Rx
• Radiologic

Brain (10)
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Hereditary hemorrhagic telengiectasia
Presence of telengiectasias in stomach duodenum
correlates with presence and number in jejunum,
however size (gt5 mm) doesnt correlate
Proctor DD. J Clin Gastroenterol 39115, 2005

• HHT may be associated with development of colonic
  adenoca polyps
• New onset anemia
• GI bleed
• COLONOSCOPY recommended

Elinav E. Int J Colorectal Dis 19(6)595, 2004
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Hereditary Hemorrhagic Telengiectasia

• Treatment
• Prevention of complications from AV
  malformations
• Management of GI bleed
• Management of epistaxis
• Genetic molecular???

Case report in NEJM, 2005 Combined syndrome of
Juvenile polyposis Hereditary hemorrhagic
telengiectasia due to germ line mutation in
MADH4 Patient was one of 15 family members with
this mutation and disease
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Dementia
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Dementia Syndromes

• Alzheimer
• Huntington

GI sxs
Dysphagia (solids liquids)
Oropharyngeal dysfunction
Higher risk of aspiration
Malnutrition
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Dementia Syndromes

• Diminished memory
• Disorientation

Delay in diagnosis
Advanced disease
Enteral feeding
Jejunostomy
PEG
NG tube
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Feeding the demented elderly

• Indications for PEG
• Obstructing upper GI cancers
• Terminal disease such as cancer or AIDS
• Neuropharyngeal dysphagia (stroke )
• Cessation of eating in dementia

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Feeding the demented elderly

• No RCT available
• Theoretically
• Prolong survival
• Palliative care
• Decrease aspiration pneumonia

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Feeding the demented elderly

• Prolonging survival ??
• Retrospective data
• Modestly prolong survival
• Modestly decrease survival
• No effect

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Feeding the demented elderly

• Palliative care ??
• Retrospective data
• Death by starvation may not be painful!
• Forceful feeding may cause pain reflux
• Thirst is not synonymous with dehydration

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Feeding the demented elderly

• Prevent aspiration pneumonia??
• Available data
• No published trial suggests that risk is
  reduced through tube feeding
• Data that jejunostomy feeding had no impact on
  pneumonia1
• Aspiration may occur between meals

1 Funicane TE, Lancet. 3491421, 1996
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Feeding the demented elderly

• No RCT available
• Theoretically
• Prolong survival
• Palliative care
• Decrease aspiration pneumonia

No survival benefit
Distressing to patient
No ? in pneumonia
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Stroke
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Stroke
Residual swallowing problems in most patients
Study comparing PEG NG for food delivery
6 week mortality 13 vs 57
Weight gain 77 vs 12
Norton B. BMJ 13 312, 1996
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Feeding in strokeCochrane meta analysis, 2005

• Unclear how dysphagic patients S/P stroke should
  be fed ???

PEG vs NG feeding
Timing of feeding
Swallowing therapy
Assess Rx strategies
Drug therapy
Nutritional supplementation
Fluid supplementation
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Feeding in strokeCochrane meta analysis, 2005
2 trials PEG ? mortality ? Rx failure
PEG vs NG feeding
No trials
Timing of feeding
Swallowing therapy
2 trials No ? dysphagia rate
Drug therapy
1 trial Nifedipine no ? mortality
Nutritional supplementation
1 trial No ? mortality
Fluid supplementation
1 trial No ? dysphagia
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Feeding in strokeCochrane meta analysis, 2005
Bottom line

• Too few studies
• Too few patients
• PEG may improve outcome vs NG
• Remaining questions
• How when to feed?
• Effect of drugs on dysphagia?

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Stroke feeding
FOOD trial
Family of 3 RCT 131 hospitals 18 countries 5033
patients Nov 96 ? Jul 03
Trial 1 routine oral supp of nl diet
Trial 2 early tube feeding outcome
Trial 3 PEG vs NG feeding

• End points
• Survival
• MRS

Dennis M. Health Technol Assess. 10(2)1, 2006
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Stroke feeding
FOOD trial

• CONCLUSIONS
• Cannot support routine diet supplementation
• Early tube feeding may substantially reduce risk
  of dying after stroke
• No difference in survival between PEG NG feeding

Dennis M. Health Technol Assess. 10(2)1, 2006
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Stroke feeding

• Pilot study
• Intermittent oro-esophageal tube feeding
• 13 acute stroke patients dysphagia
• Feeding tube to LE
• Food at 50 cc/min then removed
• Results
• IOE took 15 min
• Reduced risk of pneumonia diarrhea
• Stimulation of oral cavity pharynx

Nakajima M. Acta Neurol Scand. 113(1)36, 2006
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Stroke 2ary prophylaxis

• Aspirin is FDA approved for 2ary prophylaxis
• Benefit is well documented
• Does benefit outweigh GI risk??
• Who is at high risk of GI SE??
• Can we replace with other anti platelets??
• What is our gastroprotective strategy??

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Stroke 2ary prophylaxis

• Does benefit outweigh GI risk??
• Meta analysis (6 sec prevention trials)
• 6300 patients --- low dose aspirin(lt325 mg)
• Benefit / Risk ratio assessed
• Data suggest
• Risk of death reduction by 20
• Relative risk reduction for stroke 20 30
• 2.5 fold increase in risk of GI events
• Benefit / risk ratio 1.5 2.0

Weisman SM, Arch Intern Med. 1622197, 2002
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Stroke 2ary prophylaxis

• Who is at high risk of GI SE??
• GI bleed
• Prior GI bleed
• Prior hx of PUD/Gastritis
• Use of concomitant medications
• Age
• Comorbid conditions
• H. Pylori

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Stroke 2ary prophylaxis

• Who is at high risk of GI SE??
• H Pylori
• Observational studies
• H Pylori increases risk of
• upper GI complications with
• low dose aspirin
• H pylori 3.3
• 7.6
• Aspirin 4.8

Stack WA, Aliment Pharmacol Ther 16497, 2002
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Stroke 2ary prophylaxis
Current cardiology guidelines recommend shifting
from aspirin to clopidogrel in GI bleed or high
risk cases

• RCT evaluating
• Clopidogrel 75 mg vs aspirin 325 mg
• Conclusion
• Marginally better protection
• Moderately lesser GI SE1
• Even by EGD
• Lesser mucosal lesions2

1 CAPRIE. Lancet 3481329, 1996
2 Fort FT. Scand J Gastroenterol 120594, 2000
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Stroke 2ary prophylaxis

• Can we replace with other anti platelets??
• Middle aged man needs aspirin (2ary prophylaxis)
  has hx of GI bleed sec to NSAIDs???
• Give aspirin anyway
• Aspirin PPI
• Clopidogrel instead
• Clopidogrel PPI

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Stroke 2ary prophylaxis

• Can Clopidogrel replace the standard
  gastroprotective strategy???
• 12 month
• Randomized cardiac stroke
• Prospective patients with hx
  prevention
• Double blind of recent bleed
  of GI bleed
• Clopidogrel
  75 mg placebo
• Incidence Asp 80 mg esomep
  20 BID
• 8.6 vs 0.7

Chan FK. N Engl J Med 352238, 2005
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Stroke 2ary prophylaxis

• What is our gastroprotective strategy??
• For patients with GI risk who need aspirin the
  gold standard is prophylaxis with PPI

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Stroke 2ary prophylaxis

• Bottom line
• Aspirin should not be a life style drug.
• Benefit in stroke prophylaxis outweighs risk.
• Eradication of H. Pylori reduces GI risks
• PPI coRx is the gold standard for hi risk users.
• Replacing with other antiplatelets is
  unjustified.

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THANK YOU!

• Iyad Issa MD