Motility Disorders ESPGHAN Cape Town 2012 Jan Taminiau-Marc - - PowerPoint PPT Presentation

Motility Disorders

ESPGHAN Cape Town 2012 Jan Taminiau-Marc Benninga Academic Medical Center Amsterdam

How much can a person endure?

Patient with chronic intestinal pseudo-

• bstruction syndrome

1th day post partum: urine retention 1th year: recurrent UTI’s / constipation Profylaxis AB / lactulose 6th year: Protuding abdomen X-Abd: extremely distended bowel loops Rectum suction biopsy (-) Antroduodenale manometry (+) Picture compatible with myopathy

Differential diagnosis Motility problem

Functional Organic Spinal abnormalities Anorectal abnormalities Endocrine Cystic fybrosis Medication Munchhausen by proxy Pseudo-obstruction ????

Hirschsprung’s Disease Diagnostics?

Anorectal manometry

sleeve side hole rectal balloon IAS EAS

sleeve IAS EAS

Anorectal manometry

sleeve side hole

Anorectal catheter neonates

Rectoanal inhibitory reflex in a premature (29wks)

10 sec air insufflation 30 mmHg anal sphincter (sleeve) J Pediatr 2001;139:233-5 J Pediatr 2003;143:603-5

Rectoanal inhibition reflex in a premature (29wks)

10 sec

air insufflation

rectum 30 mmHg anal sphincter anal sphincter anal sphincter (sleeve)

rectum anal sphincter anal sphincter anal sphincter anal sphincter (sleeve)

air insufflation

40 mmHg 10 sec

4 month old neonate with Hirschsprung’s disease

Anorectal manometry

• The accuracy for the exclusion of Hirschsprung’s

by manometry varies with the age of the patients

• More accurate in older children, where studies

have suggested an accuracy of 90-100%

• Accuracy in neonates is lower (30 to 90%)

Caliber leap

Rectal suction biopsy

Normal ACE staining Increased and thickened neurites

• Pathophysiological criteria

− neuropathic CIP − myopathic CIP − unclassified (ICC’s ???)

• Etiological criteria

− congenital / familial − acquired (systemic diseases, post- infectious (CMV, EBV, HSV, polyomaviruses (JC virus) , drug- induced, ….)

Chronic intestinal pseudo-obstruction Classification

CIPS Classification

Type Myopathic Neuropathic

Infiltrative

Scleroderma, amyloidosis Early scleroderma, amyloidosis

Neurologic disease

Myotonic and other dystrophies, mitochondrial myopathy (MNGIE) Diabetes, porphyria, brain-stem tumor, MS, spinal cord transsection, dysautonomias (Shy-Drager)

Neoplastic

Paraneoplastic (small cell lung tumor), mammary ca, pancreas ca

Endocrine

Hypothyroidism, diabetes, hypoparathyroidism, pheochromocytoma (MEN II B)

Drug-induced

Anti-depressants, narcotics, anti- cholinergics, laxative abuse, smooth muscle relaxants, vincristine

Infectious

Chagas, viral (CMV, EBV, HSV)

Idiopathic

Nonfamilial hollow visceral myopathy Hirschsprung’s disease, chronic idiopathic intestinal pseudo-obstruction

Familial

Familial visceral myopathies (AD or AR), MNGIE (AR) Familial visceral neuropathies, von Recklinghausen’s disease

Patiënt with CIPS

• Full thickness biopsy

Hollow visceral myopathy

• DNA investigation

Hollow visceral myopathy → → → → no DNA investigation possible MNGIE syndrome → → → → DNA investigation possible Myoneurogastrointestinal encephalopathy syndrome Autosomal recessive pseudoobstruction, periferal neuropathy,

• phtalmoparese
• 1th year recurrent UTI’s / constipation

Profylaxis AB / lactulose

• 6th year

rectumsuctionbiopsy (-) Antroduodenal manometry (+)

Patient with CIPS

Out patient visits: ???? Bloodpicks: ???? Admissions: ????

− Diagnostics, operation, dehydration, application stoma’s, application broviac, application shunt…infection − 4x ic admission, infection

Radiology (79x):

− X-thorax, X-Abd, MRI, CT-scan, US

Surgery 20x

− Laparoscopy (full thickness biopsies), 2001 broviac catheter (TPN), application PEG and ileostoma, 2005 subtotal colectomy (distended colon, impaction with mucus), 2011 small bowel resection

Normal Gastrointestinal Motility

Components

Nerves Muscles Interstitial Cells of Cajal

C O

neuron Interstitial cell Smooth muscle cells

Interstitial cells of Cajal and nerve cells controlling smooth muscle contractility

ACh NO

Mutation of the proto-oncogene c-kit blocks development of interstitial cells and electrical rhythmicity in murine intestine +/+ wild type W/WV mutant

Ward et al., 1994

Control ACK2 treated

Torihashi et al., 1995

Anti c-kit-antibody (ACK2) treatment blocks development of ICC resulting in disturbed motility and distention of the gut

Congenital Motility Disturbances

Causes Nerves Neuropathy Muscles Myopathy ICCs ICC “disorders”

• Recurrent episodes of abdominal pain and distention
• f the abdomen resembling mechanical obstruction
• No mechanical cause (endoscopy/radiology)
• Distended bowel loops, with fluid levels
• Absence of organic, systemic or metabolic diseases

Definition CIPS

Stanghellini et al Clin Gastroenterol Hepatol 2005

• Presentation frequently in the neonatal period

(80%)

• Myopathy presents often already in utero

− Bowelobstruction, megabladder

Congenital Motility disturbances Clinical presentation

• Recurrent/ continuous signs of obstruction
• Symptoms age related / part GI tract

− Abdominal distention

88%

− Vomiting

72%

− Constipation

61%

− Abdominal pain

45%

− Failure to thrive

31%

− Diarrhea – bacterial overgrowth

28%

− Dysphagia

3%

CIPS Symptoms

CIPS Clinic

Symptoms from birth 50% Prenatal megacystis 30% Intestinal obstruction 100% Surgery 90% Urinary tract infections 90% Bacterial overgrowth 90%

• Alarm symptoms

− Recurrent/ continuous episodes of obstruction − Chronicity − Generalised gastro-intestinal dysmotility − Other organs affected

• megacystis/ hydroureter / hydronefrosis)

− Familiar − Recurrent non-diagnostic laparotomy

CIPS Clinical presentation

• Radiology

−

X-Abdomen

−

Contrast X-Ray

• Surgery

−

Avoid if possible

−

Full thickness biopsy

CIPS Diagnosis and investigation

• Test gastrointestinal motility

−

Marker studies

−

Manometry (Oesofagus, Antroduodenal, Colon)

−

Electrogastrografy (EGG)

−

Scintigrafy

• Histopathology

CIPS Diagnosis and investigation

CIPS Diagnostics

No sign of mechanical obstruction Small bowel manometry Neuropathy Myopathy

Abnormal coördination, normal amplitude contractions Normal coördination, Low amplitude contractions

Motility during fasting Postprandial

Normal antroduodenal motility

Small bowel manometry

Myopathy

CIPS Management

Multi-disciplinary treatment

• Dietitian
• Specialized nurses
• Social worker
• Psychologist
• Home nurses
• Pediatric surgeon
• Neonatologist
• Gastroenterologist

CIPS Management

• Gastric tube
• Nasoduodenal tube
• Stimulation of motility (massage, medication)
• Diet (low fiber and fat intake)

CIPS Nutrition

• PEG gastrostomy
• Jejunostomy
• Home TPN

55%

• Home TPN + enteral

35%

• Enteral feeding

10%

CIPS Medication

• Erytromycine

− Stimulates gastric emptying − Stimulates antral contractions

Reinterventions Intestinal adhesions 17 Redo enterostomy 12 Enterostomy prolapsus 7 Colectomy + ileo-rectal pull-trough 9 Pyloroplasty and gastrostomy 4 Nissen fundoplicatur 1

98 Laparotomies in 46 patients CIPS

Goulet O et al 2001

G-J Tube Ileostomy feeding venting SHORTENING THE GUT Jejunal Tube Surgery in pseudo-obstruction

CIPS Prognosis

• Overall moderate!
• Mortality 10% – 30%

− Iatrogenic complications

• Sepsis / liver failure
• Small bowel transplantation

− 1/3 dies before transplantation

• Prognosis

− Poor – neonatal onset, urinary tract involvement,

repeat surgery, myopathic disorders

− Good – presence of normal peristalsis (manometry)

CIPS (prognosis) n = 105

• 18 months TPN

30%

• Ileostomy/colostomy/jejunostomy

50%

• Mortality (1mth - 7 yr)

15%

Faure et al Dig Dis Sci 1999;953-9

• TPN dependent

25%

• Ileostomy/colostomy/jejunostomy

75%

• Mortality

25%

Heneyke et al Arch Dis Child 1999;81:21-7

CIPS (prognosis) n = 44

Decision criteria

• Permanent intestinal failure
• Permanent obstruction / aspiration
• High level of PN dependency
• End stage liver disease
• Vascular complications
• Very poor quality of life

CIPS : intestinal transplantation

CIPS : intestinal transplantation Overall results are poor and reasons are not fully analyzed

• Incidence of IF related complications including end

stage liver cirrhosis

• Multiple pre-Tx surgical procedure
• Risks related to the Tx procedure

CIPOS : intestinal transplantation

N = 85

Myopathy n=32 Neuropathy n=48 Indeterminate n=5 No SBTX n=29 SBTX n=3 Death n=7 Death n=3 SBTX n=3 No SBTX n=45 Death n=1 Death n=10 SBTX n=2 Death n=1

Mousa H et al. Dig Dis Sci. 2002

CIPOS : long-term

• utcome

62.5% post Tx death