Dataset Information

Pseudo-obstruction, stroke, and mitochondrial dysfunction: A lethal combination.

ABSTRACT:

Objectives

The m.3243A>G MTTL1 mutation is the most common cause of mitochondrial disease; yet there is limited awareness of intestinal pseudo-obstruction (IPO) in this disorder. We aimed to determine the prevalence, severity, and clinical outcome of patients with m.3243A>G-related mitochondrial disease manifesting with IPO.

Methods

In this large, observational cohort study, we assessed the clinical, molecular, and radiological characteristics of patients with genetically determined m.3243A>G-related mitochondrial disease, who presented with severe symptoms suggestive of bowel obstruction in the absence of an occluding lesion.

Results

Between January 2009 and June 2015, 226 patients harbouring the m.3243A>G mutation were recruited to the Medical Research Council Centre Mitochondrial Disease Patient Cohort, Newcastle. Thirty patients (13%) presented acutely with IPO. Thirteen of these patients had a preceding history of stroke-like episodes, whereas 1 presented 27 years previously with their first stroke-like episode. Eight patients developed IPO concomitantly during an acute stroke-like episode. Regression analysis suggested stroke was the strongest predictor for development of IPO, in addition to cardiomyopathy, low body mass index and high urinary mutation load. Poor clinical outcome was observed in 6 patients who underwent surgical procedures.

Interpretation

Our findings suggest, in this common mitochondrial disease, that IPO is an under-recognized, often misdiagnosed clinical entity. Poor clinical outcome associated with stroke and acute surgical intervention highlights the importance of the neurologist having a high index of suspicion, particularly in the acute setting, to instigate timely coordination of appropriate care and management with other specialists. Ann Neurol 2016;80:686-692.

SUBMITTER: Ng YS

PROVIDER: S-EPMC5215534 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Publications

Pseudo-obstruction, stroke, and mitochondrial dysfunction: A lethal combination.

Ng Yi Shiau YS Feeney Catherine C Schaefer Andrew M AM Holmes Carol Ellen CE Hynd Paula P Alston Charlotte L CL Grady John P JP Roberts Mark M Maguire Mellisa M Bright Alexandra A Taylor Robert W RW Yiannakou Yan Y McFarland Robert R Turnbull Doug M DM Gorman Gráinne S GS

Annals of neurology 20160919 5

<h4>Objectives</h4>The m.3243A>G MTTL1 mutation is the most common cause of mitochondrial disease; yet there is limited awareness of intestinal pseudo-obstruction (IPO) in this disorder. We aimed to determine the prevalence, severity, and clinical outcome of patients with m.3243A>G-related mitochondrial disease manifesting with IPO.<h4>Methods</h4>In this large, observational cohort study, we assessed the clinical, molecular, and radiological characteristics of patients with genetically determin ...[more]

PMID: 27453452

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Project description:BACKGROUND: Chronic idiopathic intestinal pseudo-obstruction, a syndrome of ineffectual motility due to a primary disorder of enteric nerve or muscle, is rare. AIMS: To determine the clinical spectrum, underlying pathologies, response to treatments, and prognosis in a consecutive unselected group of patients. METHODS: Cross sectional study of all patients with clinical and radiological features of intestinal obstruction in the absence of organic obstruction, associated with dilated small intestine (with or without dilated large intestine), being actively managed in one tertiary referral centre at one time. RESULTS: Twenty patients (11 men and nine women, median age 43 years, range 22-67) fulfilled the diagnostic criteria. Median age at onset of symptoms was 17 years (range two weeks to 59 years). Two patients had an autosomally dominant inherited visceral myopathy. Major presenting symptoms were pain (80%), vomiting (75%), constipation (40%), and diarrhoea (20%). Eighteen patients required abdominal surgery, and a further patient had a full thickness rectal biopsy. The mean time interval from symptom onset to first operation was 5.8 years. Histology showed visceral myopathy in 13, visceral neuropathy in three, and was indeterminate in three. In the one other patient small bowel motility studies were suggestive of neuropathy. Two patients died within two years of symptom onset, one from generalised thrombosis and the other from an inflammatory myopathy. Of the remaining 18 patients, eight were nutritionally independent of supplements, two had gastrostomy or jejunostomy feeds, and eight were receiving home parenteral nutrition. Five patients were opiate dependent, only one patient had benefited from prokinetic drug therapy, and five patients required formal psychological intervention and support. CONCLUSIONS: In a referral setting visceral myopathy is the most common diagnosis in this heterogeneous syndrome, the course of the illness is usually prolonged, and prokinetic drug therapies are not usually helpful. Ongoing management problems include pain relief and nutritional support.

Dataset Information

Pseudo-obstruction, stroke, and mitochondrial dysfunction: A lethal combination.

Objectives

Methods

Results

Interpretation

Publications

Pseudo-obstruction, stroke, and mitochondrial dysfunction: A lethal combination.

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