Chad J. Cooper

Cardiovascular Safety Profile and Clinical Experience With High-Dose Domperidone Therapy for Nausea and Vomiting

Introduction:Domperidone is a dopamine receptor antagonist with peripheral prokinetic and central antiemetic properties. Prolongation of the QTc interval with chronic use of oral domperidone in standard doses has been reported in the literature. Our goal was to investigate cardiac toxicity in patients receiving 2-fold greater doses than in previous reports. Methods:A retrospective chart review was conducted of patients with nausea (N) and vomiting (V) receiving domperidone from 2009 to 2013 under an Investigational New Drug (IND) protocol. Patient demographics, indications for therapy, clinical outcomes, cardiac symptoms and electrocardiogram tracings were reviewed. Prolonged QTc was verified if >470 milliseconds in females (F) and >450 milliseconds in males (M). Results:A total of 64 patients, 44 female (37% Hispanic, 60% white, 3% African American), were taking domperidone for diabetic gastroparesis 45%; idiopathic gastroparesis 36%; chronic N&V 8%; dumping syndrome 5%; cyclic vomiting 5% and conditioned vomiting 1%. Mean duration of therapy was 8 months (range, 3 months to 4 years). Doses ranged from 40 to 120 mg/d with 90% receiving 80 to 120 mg compared with the standard dose of 40 mg. Of note, 73% of subjects benefited from treatment with reduced nausea and vomiting. Thirty-seven patients had follow-up electrocardiograms available, and they showed that the mean QTc at baseline was 424 milliseconds ± 28.4 (SD) compared with 435 milliseconds ± 27.2 (SD) at follow-up (not significant). Ten of these patients had prolonged QTc at F/U ranging from 453 to 509 milliseconds, without any cardiovascular complaints. There was no relationship between prolonged QTc and daily dose of domperidone, body mass index or age. Conclusions:Our data indicate that at very high dosing, the prokinetic/antiemetic agent domperidone has a low risk of adverse cardiovascular events while exhibiting good clinical efficacy.

Chorea, Hyperglycemia, Basal Ganglia Syndrome (C-H-BG) in an uncontrolled diabetic patient with normal glucose levels on presentation

Patient: Female, 66 Final Diagnosis: Chorea • hyperglycemia • Basal Ganglia Syndrome (C-H-BG) Symptoms: Hemibalism • hemichorea Medication: — Clinical Procedure: — Specialty: Endocrinology and Metabolic Objective: Challenging differential diagnosis Background: Hemichorea-hemiballism (HCHB) is a spectrum of involuntary, continuous non-patterned movement involving 1 side of the body. Possible causes of HCHB include hemorrhagic or ischemic stroke, neoplasm, systemic lupus erythematosus, HHNK, Wilson’s disease, and thyrotoxicosis. This case illustrates the need to be aware of hyperglycemia as a cause of hemiballism/hemichorea, which is now referred to in the medical literature as C-H-BG (chorea, hyperglycemia, basal ganglia) syndrome. Case Report: A 66-year-old Hispanic woman presented to our care with hemiballism/hemichorea of the right arm and leg of 1 week duration. She had been admitted 3 months prior with toxic metabolic encephalopathy secondary to hyperosmolar hyperglycemic non-ketotic syndrome with a blood glucose level of 984 mg/dL. Her blood glucose level was normal but hemoglobin A1C was 12.2%. A brain MRI revealed an asymmetric T1 hyperintensity of the left putamen. This specific finding was compatible with hyperglycemia-induced hemichorea hemiballism syndrome. The hemiballism/hemichorea slowly improved over the course of the hospitalization with strict glycemic control. At the 3-month follow-up visit she had no involuntary movements of her extremities, and she had well controlled blood glucose levels and a hemoglobin A1C of 9.0. Conclusions: In a patient with normal glycemic levels but a history of uncontrolled diabetes, C-H-BG syndrome should be on the top of the differential list when the characteristic MRI findings of a hyperintensity in the basal ganglia are observed. This is a rare disease that deserves attention because it is reversible with correction of hyperglycemia. Thus, prompt recognition and treatment is essential to avoid adverse outcomes.

Paraneoplastic limbic encephalitis, an uncommon presentation of a common cancer: Case report and discussion

Patient: Female, 59 Final Diagnosis: Paraneoplastic limbic encephalitis Symptoms: Seizure • memory changes • decreased concentration Medication: Chemotherapy Clinical Procedure: Cerebral images Specialty: Hematology • Oncology Objective: Challenging differential diagnosis Background: Paraneoplastic neurological disorders (PND) are defined as remote effects on the nervous system that are not caused directly by the tumor, its metastases, or metabolic disruptions. This syndrome occurs in less than 1 per 10,000 patients diagnosed with a malignancy. Many antibodies are found in the central nervous system in PND, the most well known are Anti-Hu, Tr, CV2 Ta, Yo, Ri and amphiphysin. Paraneoplastic limbic encephalitis occurs due to involvement of the limbic system secondary to an autoimmune response to neurons of the brain provoked by the antibodies. Patients, thus, present with seizures, changes in mood, memory, and personality. Case Report: Fifty-nine years-old female patient presented with seizures, decreased concentration and memory changes. Laboratory workup was remarkable for hyponatremia. Further workup included brain computerized tomography (CT) and magnetic resonance imaging (MRI), which suggested a diagnosis of encephalitis for limbic encephalitis. Anti-Hu, anti-Ma and NMDA-receptor antibodies were requested of which Anti Hu antibodies were positive. Transbronchial biopsy was obtained which confirmed the diagnosis of small cell lung cancer. Conclusions: A very high index of suspicion should thus be present when patients present with paraneoplastic abnormalities. It must be emphasized that limbic encephalitis (LE) occurs at an early stage of the disease development and therefore the detection of paraneoplastic LE can lead to a quicker identification of the underlying malignancy and a better outcome.

A Complicated Case of an Immunocompetent Patient with Disseminated Nocardiosis

Nocardia species are aerobic, gram positive filamentous branching bacteria that have the potential to cause localized or disseminated infection. Nocardiosis is a rare disease that usually affects immunocompromised patients and presents as either pulmonary, cutaneous or disseminated nocardiosis. Forty-two year-old hispanic male presented to our care with bilateral lower extremity weakness, frontal headache, subjective fever, nausea, and vomiting. Brain computed tomography (CT) revealed multiple hyperdense lesions with vasogenic edema in the frontal, parietal and left temporal lobes. Chest CT demonstrated bilateral cavitary nodules in the lung and right hilar lymphadenopathy. Brain magnetic resonance imaging revealed multiple bilateral supratentorial and infratentorial rim enhancing lesions involving the subcortical gray-white matter interface with vasogenic edema. Patient was started on empiric therapy for unknown infectious etiology with no response. He eventually expired and autopsy findings revealed a right hilar lung abscess and multiple brain abscesses. Microscopic and culture findings from tissue sample during autopsy revealed nocardia wallacei species with multidrug resistance. The cause of death was stated as systemic nocadiosis (nocardia pneumonitis and encephalitis). The presence of simultaneous lung and brain abscesses is a reliable indication of an underlying Nocardia infection. An increased awareness of the various presentations of nocardiosis and a high index of clinical suspicion can help in a rapid diagnosis and improve survival in an otherwise fatal disease. This case highlights the importance of obtaining a tissue biopsy for definitive diagnosis on the initial presentation when an infectious process is considered in the differential diagnosis and early treatment can be initiated.

West Nile virus encephalitis induced opsoclonus-myoclonus syndrome

West Nile virus (WNV) is an arthropod borne neurotropic single stranded RNA flavivirus with <1% developing presenting with neurological disease. Immunocompromised and elderly patients are more prone to developing WNV meningitis or encephalitis. Definitive diagnosis of WNV meningoencephalitis is a combination of clinical suspicion and cerebrospinal fluid (CSF) serology. Forty-eight year old Caucasian female presented with a sudden onset of altered mental status after being found unresponsive. She was confused with intermittent bouts of alertness/lethargy and unintelligible responses to questioning. Her medical problems included endometrial cancer that was in remission after undergoing a total abdominal hysterectomy with bilateral salpingectomy and postoperative chemotherapy with paclitaxel and carboplatin. Pertinent physical examination revealed muscle strength that was significantly decreased, nuchal rigidity and +2 pitting edema of both lower extremities. Computed tomography and magnetic resonance imaging of the brain were negative for any intracranial pathology. CSF analysis was consistent with aseptic meningitis with all CSF serology being negative except for positive WNV antibody. A few days after being admitted she developed involuntary random movements of her eyes and generalized jerking movements (myoclonus). This was determined to be opsoclonus myoclonus syndrome (OMS) induced by the WNV meningoencephalitis. She then received five consecutive days of plasmapheresis with a significant improvement in her neurological status. Opsoclonus-myoclonus syndrome (OMS) is a rare neurological disorder associated with chaotic multidirectional eye movements, myoclonus and less frequently cerebellar ataxia. OMS affects as few as 1 in 10,000,000 people per year. The pathogenesis is not fully understood with the majority of cases of opsoclonus-myoclonus syndrome being idiopathic. According to current medical literature there have only been two previous case reports of opsoclonus myoclonus syndrome associated with WNV encephalitis.

Rapid or normal gastric emptying as new supportive criteria for diagnosing cyclic vomiting syndrome in adults.

Background Cyclic vomiting syndrome (CVS) in adults is a disorder characterized by recurrent and stereotypic episodes of severe nausea, vomiting and abdominal pain separated by symptom-free intervals. Our goal was to investigate gastric emptying (GE) in CVS patients. Material/Methods This was a retrospective study of 30 adult patients who met Rome III diagnostic criteria for CVS. Rapid GE was defined using two different predefined criteria as either <50% isotope retention or <65% isotope retention at 1st hour and/or <20% at 2nd hour. Results Of the 30 patients (25 had 4-hr GE) diagnosed with CVS, 22 were females and 8 males with a mean age of 39 years. Overall, 20 (80%) of the 25 CVS patients met the predefined criteria of <50% retention for rapid GE in the first hour. Fifteen (60%) met the 2-hour criteria for rapid emptying of <20% retention. Five (16.6%) patients of the 25 had a normal GE with a mean retention at the first hour of 65% (52–78%). Nine (36%) also met another predefined criteria of <35% retention for rapid GE in the first hour. Sixteen (64%) met criteria for normal GE. Conclusions (1) In adult CVS patients, GE is either rapid or normal, clearly distinguishing this entity from gastroparesis. (2) Cyclic vomiting syndrome is an important new etiology to explain the finding of rapid GE on a radionuclide test. (3) We suggest that rapid gastric emptying should be added as supportive criteria for diagnosing CVS in adults.

Hepatitis C- and HIV-induced porphyria cutanea tarda

Patient: Male, 47 Final Diagnosis: Porphyria cutanea tarda Symptoms: Chills • cough dry • thumb swelling Medication: — Clinical Procedure: — Specialty: Metabolic Disorders and Diabetics Objective: Challenging differential diagnosis Background: Porphyria cutanea tarda (PCT) is the most common type of the porphyria. It occurs due to the deficiency of enzyme uroporphyrinogen decarboxylase (UROD), which is the fifth enzyme in the biosynthesis of heme and catalyzes the conversion of uroporphyrinogen to coproporphyrinogen. The risk factors for PCT include hereditary hemochromatosis, hepatitis C infection, ethanol abuse, estrogen use, HIV, smoking, chlorinated polycyclic aromatic hydrocarbons, and hemodialysis. Case Report: A 47-year-old Hispanic man presented with right thumb swelling, redness, and pain for approximately 1 week. Past medical history included HIV/AIDS, hepatitis C infection, alcohol abuse, heroin abuse, and CMV retinitis. Skin examination revealed blistering and hypo/hyper pigmented lesions over the dorsal aspects of the hands and other sun-exposed areas. Serum porphyrins were discovered to be elevated. The quantitative urine porphyrins revealed elevation of uroporphyrins, heptacarboxyl-porphyrins, hexacarboxy-porphyrins, pentacarboxyl-porphyrins and coproporphyrin. Genetic mutation of UROD was not detected. Due to the classic cutaneous lesions, laboratory findings, and associated risk factors, we were able to confirm our suspicion of the sporadic (type 1) form of PCT. Conclusions: A strong correlation has been demonstrated between the sporadic (type 1) form of PCT and hepatitis C virus (HCV) infection in multiple studies. The mechanism through which HCV infection may cause or trigger PCT is unknown. PCT has been described for many years, but still eludes the differential diagnosis in a patient with cutaneous findings. The uniqueness of our case is the possibility that combined risk factors have an effect on PCT.

Dural arteriovenous fistula discovered in patient presenting with recent head trauma

Patient Male, 32 Final Diagnosis: Dural arterio-venous fistula Symptoms: Eye redness • post-trauma headache • tinnitus Medication: — Clinical Procedure: Fistula embolization Specialty: Neurology Objective: Mistake in diagnosis Background: A dural arteriovenous fistula (DAVF), is an abnormal direct connection (fistula) between a meningeal artery and a meningeal vein or dural venous sinus. The pathogenesis of DAVF still remains unclear. Sinus thrombosis, head trauma, chronic central nervous system, hypercoagulable state, surgery, and hormonal influence are the pre-disposing factors that initiate this disease. The symptoms experienced by the patient will depend on the location of the fistula. Case Report: Thirty-two year old Hispanic male who presented one day after a rear ended motor vehicle collision (MVC) with a severe throbbing headache in the left parietal region, left eye redness but no retro-orbital pain and tinnitus in the left ear. He was initially misdiagnosed to have a carotid-cavernous fistula but upon cerebral angiogram was actually diagnosed with a dural arterio-venous fistula in the posterior fossa venous system followed by successful embolization of the fistula. Conclusions: A cerebral angiography is the gold standard for detection and characterization of a DAVF and will distinguish it from a CCF. Endovascular surgery involves a catheter-based technique for embolization of the lumen of arteries feeding the DAVF, or directly into the vein draining the DAVF. It is very important to recognize the typical findings of patients presenting with a DAVF then quickly proceeding with a cerebral angiogram to determine the exact location of the fistula and the appropriate treatment plan. By diagnosing and treating a DAVF as early as possible, the associated fatal complications can be averted.

Interferon-alpha-induced sarcoidosis in a patient being treated for hepatitis C

Patient: Female, 43 Final Diagnosis: — Symptoms: Diarrhea • generalized weakness • headache • lightheadedness • nausea • rash • short of breath • vomiting Medication: — Clinical Procedure: — Specialty: Pulmonology Objective: Rare diseae Background: IFN-alpha-2b in combination with ribavirin is now the standard of care for the treatment of hepatitis C. Sarcoidosis is a chronic multisystem granulomatous disorder characterized by noncaseating granulomas in the involved organs. The pathologic hallmark of sarcoidosis is the presence of noncaseating granulomas in the interstitium that typically involve the lymphatics. Case Report: A 43-year-old woman presented to our care with 2-week history of nausea, vomiting, diarrhea, shortness of breath, migraine headache, maculopapular rash, generalized weakness, and lightheadedness. She had been treated for hepatitis C with telaprevir, ribavirin, and interferon-alpha-2b for 6 months. Chest radiograph showed bilateral diffuse prominence of bronchovascular markings. CT of the chest revealed bilateral diffuse centrilobular nodules with associated intralobular septal thickening, thickening of the central peribronchovascular interstitium, nodularity of the major fissures, and mediastinal lymphadenopathy. These findings were suspicious for atypical pulmonary sarcoidosis, possibly interferon-induced. The pathology of the mediastinal lymph node biopsy revealed noncaseating granulomatous inflammation consistent with the diagnosis of pulmonary sarcoidosis. Pathology of the skin punch biopsy showed giant-cell granulomatous inflammation without necrosis. The patient was started on prednisone 40 mg daily with a steroid tapering course for 8 weeks. Conclusions: The management of IFN-induced sarcoidosis includes the discontinuation of IFN therapy with or without the administration of systemic corticosteroids. With the increasing prevalence of HCV in the United States, it is likely that more IFN-alpha-induced sarcoidosis will be encountered by clinicians.

Esophageal perforation post pneumatic dilatation for achalasia managed by esophageal stenting

Patient: Female, 82 Final Diagnosis: Achalasia Symptoms: Nocturnal regurgtation • weight loss Medication: — Clinical Procedure: Esophageal stenting Specialty: Gastroenterology • Hepatology Objective: Unusual or unexpected effect of treatment Background: Pneumatic dilatation is one of the most effective methods for treating achalasia. Esophageal perforation is the most serious complication after pneumatic dilatation and has been reported to occur in the range of 1 to 4.3%. The appropriate management of esophageal perforation can range from conservative medical treatment to surgical intervention. Case Report: We report a case of an 82-year-old male who had an 8 month history of dysphagia for solid and liquids, a 10 lb weight loss and nocturnal regurgitation. The diagnosis of achalasia was established by endoscopic; barium and manometric criteria. He underwent a pneumatic dilation with a 30 mm Rigiflex balloon. A confined or limited esophageal perforation projecting into the mediastinum and located 1–2 cm above the diaphragm was confirmed by a gastrografin swallow study performed immediately after the procedure. There was some accompanying epigastric abdominal pain. Patient was treated later that day by placing a fully covered metallic esophageal stent in addition to antibiotics, proton pump inhibitor, and fasting. Patient was discharged home 3 days later able to eat liquid-soft foods. Follow up endoscopy 2 weeks later and a gastrografin swallow showed a completely healed perforation and the stent was removed. Symptomatically he has done well, with no dysphagia or heartburn at six and twelve months follow up. Conclusions: Early esophageal stenting for esophageal perforation after pneumatic dilation for achalasia is a treatment option which accelerates healing shortens recovery period, as well as decreasing hospital stay and costs.