[CIS PIDD] [cis-pidd] neurodegeneration in CHARGE+DiGeorge Patient

Sat Dec 23 20:14:50 EST 2017

Dr. Dulek:

I concur with Dr. Atkinson's suggestion.  The "universal pathogen PCRs" are sometimes helpful.  I would send both CSF and BAL fluid (if available).  The only thing better would be next-gen sequencing for pathogens -- but this requires a high powered laboratory at one's disposal.

I'm assuming the patient is CD4 lymphopenic.  Has there been PCR-based diagnostics for Toxoplasma or Pneumocystis?  Fungal urine/blood antigen testing?  "Periventricular hyperinstensity" may be early cerebral toxoplasmosis, especially if the CD4 count was low-ish.  (Absence of a cat at home does not rule this out as a possibility ... I've seen bad cases without a cat exposure history)

Long-shot suggestions, certainly.  But straightforward to rule out.

Good luck in this case.

   - K

Karl O. A. Yu, M.D., Ph.D., F.A.A.P.
Scientist II and Assistant Director, Center for Infectious Diseases and Immunology
RGH Research Institute | Rochester General Hospital | Rochester Regional Health
1425 Portland Ave., Rochester, NY   14621
Tel  585-922-3709  |  Fax  585-922-2415

________________________________________
From: cis-pidd at lyris.dundee.net [cis-pidd at lyris.dundee.net] on behalf of CIS-PIDD [cis-pidd at lists.clinimmsoc.org]
Sent: Saturday, December 23, 2017 6:12 PM
To: CIS-PIDD
Subject: RE:[cis-pidd] neurodegeneration in CHARGE+DiGeorge Patient

I suggest you send spinal fluid for 16S/NGS testing at the University of Washington and if that is negative, have them do the analogous testing offered for mycobacterial and fungal agents.

https://depts.washington.edu/molmicdx/mdx/tests/NGS16S.shtml

Prescott

T. Prescott Atkinson, MD PhD, Professor and Director
Division of Pediatric Allergy, Asthma & Immunology
University of Alabama at Birmingham
Tel 205-638-6457
Fax 205-638-2833
_________________________________
From: cis-pidd at lyris.dundee.net [mailto:cis-pidd at lyris.dundee.net] On Behalf Of CIS-PIDD
Sent: Friday, December 22, 2017 12:44 PM
To: CIS-PIDD
Subject: [cis-pidd] neurodegeneration in CHARGE+DiGeorge Patient

I am writing to see if anyone has experience with diffuse CNS neurodegeneration without focality on MRI in a patient with CHARGE and atypical complete DGS.   We are planning to send WES but this will likely not impact his current situation.  His prognosis is clearly poor but we would love to provide family with some explanation.

The patient is a 13 mo old male with CHD7 confirmed CHARGE syndrome and atypical complete DGS who transferred to our institution in September.  He was admitted 6 weeks ago with RSV and treated successfully with ribavirin.  2 weeks after discharge, he was seen in clinic with increased fussiness.  KUB showed possible free air; he was readmitted and abdominal CT showed colonic pneumatosis.  He was started on zosyn and bowel rest.  It was felt that perhaps steroids had contributed (he weaning off and was on 0.3mg/kg/day at that time), so a more aggressive wean was started.  He was on cyclosporine as well.

3 days into the admission, he was noted to be difficult to arouse.  MRI at that time (11/20) showed extensive white matter loss as compared to a CT scan from his previous institution from May of this year.  LP showed slight pleocytosis (12 nucleated cells; 26% Neutrophils; 37% lymphocytes; 37% monocytes)  normal protein, normal glucose) with negative bacterial, fungal and viral cultures.  Negative CSF studies include viral PCRs (HSV, VZV, HHV6, JC virus, enterovirus), viral culture, cryptococcal antigen, AFB/bacterial/fungal cultures, and CSF oligoclonal bands.  Urine organic/Serum amino acids are pending.  Since that initial mental status decline he has remained non-interactive.  Repeat MRI (12/15/17) showed no acute progression of white matter volume loss.  There is no evidence of stroke, no post-contrast enhancement, no focal areas of hyperintensity apart from some mild periventricular hyperinstensity that the neuroradiologists felt was more secondary to the volume loss than a primary lesion.

He has remained on broad spectrum antibiotics in addition to fungal and viral prophylaxis.  In the first week, he did not require increased respiratory support, but over the past 7 days, he escalated to CPAP and finally was intubated on Monday due to hypercarbia.  Chest CT showed no evidence of lower respiratory tract disease and he has required minimal pressures/vent support.  Neurology has been involved and he has had no clear evidence of seizures on EEG.  Since intubation he has not initiated spontaneous respirations.  He has maintained normal BP and has not had any changes in liver or kidney function.

Dan

Daniel Dulek, MD
Assistant Professor, Pediatric Infectious Diseases
Director, Peter F. Wright Immunocompromised Host Pediatric ID Service
Vanderbilt University School of Medicine and the Monroe Carell, Jr. Children’s Hospital at Vanderbilt
D-7234 Medical Center North
1161 21st Avenue South, Nashville, TN 37232-2581

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