Case Study 2
36-year-old white male who had been in remarkable health until December 2004 when he had self-limited nausea and vomiting, followed by mild fatigue and myalgia. He used to run 6 miles every other day but had to cut back over the next several months. In April 2005, the patient had sudden onset of vertigo, nausea and vomiting, then had dizziness, headache and nausea two weeks later. In July 2005, the patient had severe diarrhea, nausea, dizziness, blurred vision, cross-eyed feeling, dysequilibrium, flu-like symptoms and post nasal drip. By the next month the patient had severe pain between the eyes, daily dizziness along with other symptoms. In November/December the post nasal drip improved. The patient had upper stomach pain and was found to have a gall bladder polyp by ultrasound. The patient had GERD, Gastro Esophageal Reflex Disease, along with other symptoms. The patient had a number of emergency room visits for severe GERD symptoms. Eventually a gastric-emptying study showed gastroparesis of the antrum.
In May 2006, the patient had diffuse muscle fasciculations and numbness of his hands and feet, sharp jerking shooting pain all over the body. In June 2006 the patient had a spinal tap that was completely normal. Lyme's disease antibody was borderline positive although the patient had never been in the areas endemic for Lyme's disease. An Infectious Disease physician felt the patient did not have active Lyme's disease. In the fall of 2006 the patient had a tilt test that showed postural orthostatic tachycardia. The patient was given atenolol and felt much worse. The patient has not worked since September 2006. Eventually the patient was treated with 6 months of intravenous Rocephin for Lyme's disease without improvement of his symptoms. EBV and CMV IgG were positive. All the regular blood test results including CBC, chemistry panel, TFT, CT scan, MRI scan, EMG continued to be normal. The patient was given Valcyte for 3 months without benefit. Subsequent MRI scan done showed a punctate white lesion on the surface of the left parietal lobe which was not confirmed on a repeat MRI scan done six months later. Energy level was better for 3 out of 7 days but he could only do 3 hours of light activity with frequent breaks. On the other 4 days the patient was practically bedridden with energy level 0-1/10. He continues to have numbness, stabbing pain in the fingers and toes especially when he sits down, along with neck stiffness.
Routine laboratory studies including TFT, ANA, RF, CRP, ESR, H. pylori antibody. Lyme's disease antibody done at Stoney Brook Laboratory, celiac disease panel, urine heavy metal screening, SS-A, SS-B antibodies were negative. AST and ALT were mildly elevated on two determinations. CSF, MS panel on June 3, 2006 was negative. CT of the sinus showed small polyps within the maxillary sinuses. ENG and hearing test were normal. EGD and colonoscopy in January 2006 showed a single sigmoid polyp. Stool studies were negative. The patient was treated with tapering course of prednisone in November 2005. In June 2008, CVB 4 antibody titer was 1:640 (<1:10).
PHYSICAL EXAMINATION: The patient does not look sick. Throat- 2+ throat inflammation. Neck minimal, tender lymph nodes, mildly tendery. Abdomen� mild epigastric, lower quadrant tenderness. Extremities- no muscle tenderness. Neurological � normal.
Special laboratory tests done at EV Med Research: Blood positive for 355 copies/ml of EV RNA. Stomach antrum biopsy showed extensive enterovirus protein (as shown, 400 x magnification).
ASSESSMENT: Chronic fatigue syndrome with documented orthostatic hypotension, chronic dizziness and other neurological symptoms, was most likely due to a chronic enterovirus infection since the initial symptoms of infection were gastrointestinal. These viruses would enter through the GI tract by eating contaminated food or drinking water, then disseminate to the brain, spinal cord, muscles and heart, most often through the blood but sometimes in a retrograde manner through the nerve fibers, as has been documented with enterovirus 71. The brain stem symptoms and orthostatic hypertension are all suggestive of viral infection in those areas, but the lesions are probably too small to be seen by the usual imaging studies such as CT and MRI scans. It is interesting that there is a lag time of several months between the initial GI symptoms and the subsequent brain symptoms. This is actually typical of many of the patients who did not have flu-like symptoms immediately before the onset of the CNS or muscles symptoms. The best explanation is that viruses disseminated to the secondary sites, such as brain may not manifest until the initial immune response gradually subsides.
Although the diagnosis of Lyme's disease has been implicated in the endemic areas by a few investigators, this patient was never in the endemic areas for Borrelia burgdorferi., and the final serology done in a reputable laboratory showed totally negative results. Furthermore, the continuing GI symptoms or even respiratory symptoms in other patients are inconsistent with Lyme's disease, since this infection is transmitted by a tick bite and dissemination has been documented in the joints, heart and the brain. The lack of response to valcyte is not surprising since the drug is used for herpes viruses and yet the patient has an enterovirus infection.
The treatment for orthostatic hypotension is not ideal. Many of the patients did not tolerate beta blocker. Alternatively, midodrine starting at 2.5 mg t.i.d. then work up to 5 mg t.i.d. and increase further as tolerated, may be helpful for some patients. Antiviral therapy is still the key to control enterovirus infection, which will require development.
36-year-old white male who had been in remarkable health until December 2004 when he had self-limited nausea and vomiting, followed by mild fatigue and myalgia. He used to run 6 miles every other day but had to cut back over the next several months. In April 2005, the patient had sudden onset of vertigo, nausea and vomiting, then had dizziness, headache and nausea two weeks later. In July 2005, the patient had severe diarrhea, nausea, dizziness, blurred vision, cross-eyed feeling, dysequilibrium, flu-like symptoms and post nasal drip. By the next month the patient had severe pain between the eyes, daily dizziness along with other symptoms. In November/December the post nasal drip improved. The patient had upper stomach pain and was found to have a gall bladder polyp by ultrasound. The patient had GERD, Gastro Esophageal Reflex Disease, along with other symptoms. The patient had a number of emergency room visits for severe GERD symptoms. Eventually a gastric-emptying study showed gastroparesis of the antrum.
In May 2006, the patient had diffuse muscle fasciculations and numbness of his hands and feet, sharp jerking shooting pain all over the body. In June 2006 the patient had a spinal tap that was completely normal. Lyme's disease antibody was borderline positive although the patient had never been in the areas endemic for Lyme's disease. An Infectious Disease physician felt the patient did not have active Lyme's disease. In the fall of 2006 the patient had a tilt test that showed postural orthostatic tachycardia. The patient was given atenolol and felt much worse. The patient has not worked since September 2006. Eventually the patient was treated with 6 months of intravenous Rocephin for Lyme's disease without improvement of his symptoms. EBV and CMV IgG were positive. All the regular blood test results including CBC, chemistry panel, TFT, CT scan, MRI scan, EMG continued to be normal. The patient was given Valcyte for 3 months without benefit. Subsequent MRI scan done showed a punctate white lesion on the surface of the left parietal lobe which was not confirmed on a repeat MRI scan done six months later. Energy level was better for 3 out of 7 days but he could only do 3 hours of light activity with frequent breaks. On the other 4 days the patient was practically bedridden with energy level 0-1/10. He continues to have numbness, stabbing pain in the fingers and toes especially when he sits down, along with neck stiffness.
Routine laboratory studies including TFT, ANA, RF, CRP, ESR, H. pylori antibody. Lyme's disease antibody done at Stoney Brook Laboratory, celiac disease panel, urine heavy metal screening, SS-A, SS-B antibodies were negative. AST and ALT were mildly elevated on two determinations. CSF, MS panel on June 3, 2006 was negative. CT of the sinus showed small polyps within the maxillary sinuses. ENG and hearing test were normal. EGD and colonoscopy in January 2006 showed a single sigmoid polyp. Stool studies were negative. The patient was treated with tapering course of prednisone in November 2005. In June 2008, CVB 4 antibody titer was 1:640 (<1:10).
PHYSICAL EXAMINATION: The patient does not look sick. Throat- 2+ throat inflammation. Neck minimal, tender lymph nodes, mildly tendery. Abdomen� mild epigastric, lower quadrant tenderness. Extremities- no muscle tenderness. Neurological � normal.
Special laboratory tests done at EV Med Research: Blood positive for 355 copies/ml of EV RNA. Stomach antrum biopsy showed extensive enterovirus protein (as shown, 400 x magnification).
ASSESSMENT: Chronic fatigue syndrome with documented orthostatic hypotension, chronic dizziness and other neurological symptoms, was most likely due to a chronic enterovirus infection since the initial symptoms of infection were gastrointestinal. These viruses would enter through the GI tract by eating contaminated food or drinking water, then disseminate to the brain, spinal cord, muscles and heart, most often through the blood but sometimes in a retrograde manner through the nerve fibers, as has been documented with enterovirus 71. The brain stem symptoms and orthostatic hypertension are all suggestive of viral infection in those areas, but the lesions are probably too small to be seen by the usual imaging studies such as CT and MRI scans. It is interesting that there is a lag time of several months between the initial GI symptoms and the subsequent brain symptoms. This is actually typical of many of the patients who did not have flu-like symptoms immediately before the onset of the CNS or muscles symptoms. The best explanation is that viruses disseminated to the secondary sites, such as brain may not manifest until the initial immune response gradually subsides.
Although the diagnosis of Lyme's disease has been implicated in the endemic areas by a few investigators, this patient was never in the endemic areas for Borrelia burgdorferi., and the final serology done in a reputable laboratory showed totally negative results. Furthermore, the continuing GI symptoms or even respiratory symptoms in other patients are inconsistent with Lyme's disease, since this infection is transmitted by a tick bite and dissemination has been documented in the joints, heart and the brain. The lack of response to valcyte is not surprising since the drug is used for herpes viruses and yet the patient has an enterovirus infection.
The treatment for orthostatic hypotension is not ideal. Many of the patients did not tolerate beta blocker. Alternatively, midodrine starting at 2.5 mg t.i.d. then work up to 5 mg t.i.d. and increase further as tolerated, may be helpful for some patients. Antiviral therapy is still the key to control enterovirus infection, which will require development.