Fatal gastroparesis in a patient with Parkinson's disease

Authors

  • Neal Hermanowicz MD

    1. Department of Neurology, University of California, Irvine, California, USA
    2. Phillip & Carol Traub Center for Parkinson's Disease, Eisenhower Medical Center, Rancho Mirage, California, USA
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Fatal Gastroparesis in a Patient with Parkinson's Disease

Gastrointestinal (GI) dysfunction was described by James Parkinson in his 1817 monograph on the disease that now bears his name, and this remains an area of interest as an early manifestation of the disorder possibly preceding the appearance of motor symptoms.1 I report here a case of a patient with Parkinson's disease (PD) with associated gastroparesis that was evident and prominently troubling early in the illness course and ultimately proved fatal.

This male patient was diagnosed with PD at the age of 70 with initial symptoms of tremor of his right limbs present intermittently for a 2-year period. The neurological examination at the time of diagnosis demonstrated typical findings of PD, including a conspicuous right hand tremor at rest, subtle rigidity of the right arm, and bradykinesia. Symptoms improved with initial treatment with pramipexole followed later with the addition of carbidopa/levodopa. On this medication regimen and 2.5 years after his diagnosis of PD, the patient first complained of symptoms of nausea and abdominal discomfort. Treatment with trimethobenzamide hydrochloride, pantoprazole, and esomeprazole did not provide relief. Gastroparesis was diagnosed by a gastroenterologist who observed during endoscopy food in the patient's stomach hours after he had last eaten. Pramipexole was withdrawn with no positive impact on the patient's GI distress, which persisted and escalated. At his last visit with his neurologist, at age 76, 5.5 years after being diagnosed with PD, the patient weighed 148 pounds, representing a 31 pound weight loss. He scored 15.0 on the Motor Section of the UPDRS on a medication regimen of pramipexole 0.5 mg and carbidopa/levodopa 25/100 one tablet of each three times daily. Two weeks after this last visit, he was hospitalized for repetitive vomiting. He declined invasive procedures and developed aspiration pneumonitis leading to sepsis, multiorgan failure, and his death. A postmortem examination was not conducted.

The etiology of gastroparesis in PD is attributed to autonomic dysfunction, which may arise from central or peripheral locations. The stomach, intestine and all but the distal segment of the colon receive prokinetic signals from parasympathetic innervation arising from neurons in the dorsal motor nucleus of the vagus nerve. This nucleus is a site of pathology in PD, which may be the source of impaired gut motility. Alternatively, Lewy body formation in the peripheral plexi of the myenteric nervous system has long been recognized in some patients with PD, and this, too, could be a contributing source of disordered gut motility.2

Gastroparesis in patients with PD has been reported to correlate with severity of motor impairment.3 Striking in this case is that the examination showed mild motor findings on a modest medication regimen, whereas the GI symptoms were evident early, they were progressive and ultimately fatal. Death due to gastroparesis is rare regardless of etiology. Review of the literature did not reveal previous published reports of death attributable to gastroparesis in a patient with PD.

GI dysfunction may represent an early indicator of the pathological processes of PD.1 The five neuropathological stages of PD proposed by Braak et al.4 describe early involvement of the dorsal motor nucleus of the vagus nerve (Stage 1), preceding appearance of neuronal degeneration in the substantia nigra (Stage 3). This may explain the possible appearance of GI symptoms early or prior to motor manifestations of the disease. Evidence of α-synuclein aggregates in peripheral autonomic neurons in surgical biopsy specimens derived from patients undiagnosed with PD points to another possible mechanism that could lead to GI dysfunction early in the illness.5

In one series of 146 cases of gastroparesis the largest percentage of cases (36%) were idiopathic.6 Although, unlike PD, idiopathic gastroparesis is more common among women, it may be fruitful to study men to ascertain whether some have subtle motor impairment, olfactory dysfunction, REM behavior sleep disorder, CNS dopaminergic abnormalities detectable by functional imaging, genetic abnormalities associated with PD, or later develop clinical parkinsonism.

Neal Hermanowicz MD* †, * Department of Neurology, University of California, Irvine, California, USA, † Phillip & Carol Traub Center for Parkinson's Disease, Eisenhower Medical Center, Rancho Mirage, California, USA.

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