BEUDAMED
    FDA Adverse Event Injury Summary report: N

    KINETRA

    MDR report key: 3504583 · Received December 9, 2013

    Report

    Report Number
    3007566237-2013-03963
    Event Type
    Injury
    Date Received
    December 9, 2013
    Date of Event
    October 3, 2013
    Report Date
    November 12, 2013
    Manufacturer
    MEDTRONIC NEUROMODULATION
    Product Code
    MFR
    PMA / PMN Number
    H050003
    Adverse Event
    Yes
    Product Problem
    Yes
    Report Source
    Manufacturer report
    Reporter Location
    UT, US
    Reporter Occupation
    PHYSICIAN

    Narratives

    Additional Manufacturer Narrative · 1

    THE ACTUAL EVENT DATES WERE NOT PROVIDED. THIS DATE IS BASED ON THE DATE OF PUBLICATION OF THE ARTICLE. IT WAS NOT POSSIBLE TO ASCERTAIN SPECIFIC DEVICE INFORMATION FROM THE ARTICLE OR TO MATCH THE EVENTS REPORTED WITH PREVIOUSLY REPORTED EVENTS. CONCOMITANT PRODUCTS: PRODUCT ID NEU_UNKNOWN_LEAD, LOT # UNKNOWN, PRODUCT TYPE LEAD. (B)(4).

    Description of Event or Problem · 1

    O'RAWE, J. A., FANG, H., RYNEARSON, S., ROBISON, R., KIRULUTA, E. S., HIGGINS, G., EILBECK, K., REESE, M. G., LYON, G. J. INTEGRATING PRECISION MEDICINE IN THE STUDY AND CLINICAL TREATMENT OF A SEVERELY MENTALLY ILL PERSON. SUMMARY: IN RECENT YEARS, THERE HAS BEEN AN EXPLOSION IN THE NUMBER OF TECHNICAL AND MEDICAL DIAGNOSTIC PLATFORMS BEING DEVELOPED. THIS HAS GREATLY IMPROVED OUR ABILITY TO MORE ACCURATELY, AND MORE COMPREHENSIVELY, EXPLORE AND CHARACTERIZE HUMAN BIOLOGICAL SYSTEMS ON THE INDIVIDUAL LEVEL. LARGE QUANTITIES OF BIOMEDICAL DATA ARE NOW BEING GENERATED AND ARCHIVED IN MANY SEPARATE RESEARCH AND CLINICAL ACTIVITIES, BUT THERE EXISTS A PAUCITY OF STUDIES THAT INTEGRATE THE AREAS OF CLINICAL NEUROPSYCHIATRY, PERSONAL GENOMICS AND BRAIN-MACHINE INTERFACES. A SINGLE PERSON WITH SEVERE MENTAL ILLNESS WAS IMPLANTED WITH THE MEDTRONIC RECLAIM_ DEEP BRAIN STIMULATION (DBS) THERAPY DEVICE FOR OBSESSIVE COMPULSIVE DISORDER (OCD), TARGETING HIS NUCLEUS ACCUMBENS/ANTERIOR LIMB OF THE INTERNAL CAPSULE. PROGRAMMING OF THE DEVICE AND PSYCHIATRIC ASSESSMENTS OCCURRED IN AN OUTPATIENT SETTING FOR OVER TWO YEARS. HIS GENOME WAS SEQUENCED AND VARIANTS WERE DETECTED IN THE ILLUMINA WHOLE GENOME SEQUENCING CLINICAL LABORATORY IMPROVEMENT AMENDMENTS (CLIA)-CERTIFIED LABORATORY. WE REPORT HERE THE DETAILED PHENOTYPIC CHARACTERIZATION, CLINICAL-GRADE WHOLE GENOME SEQUENCING (WGS), AND TWO-YEAR OUTCOME OF A MAN WITH SEVERE OCD TREATED WITH DBS. SINCE IMPLANTATION, THIS MAN HAS REPORTED STEADY IMPROVEMENT, HIGHLIGHTED BY A STEADY DECLINE IN HIS YALE-BROWN OBSESSIVE COMPULSIVE SCALE (YBOCS) SCORE FROM_38 TO A SCORE OF_25. A RECHARGEABLE ACTIVA RC NEUROSTIMULATOR BATTERY HAS BEEN OF MAJOR BENEFIT IN TERMS OF FACILITATING A DEGREE OF STABILITY AND CONTROL OVER THE STIMULATION. HIS PSYCHIATRIC SYMPTOMS RELIABLY WORSEN WITHIN HOURS OF THE BATTERY BECOMING DEPLETED, THUS PROVIDING CONFIRMATORY EVIDENCE FOR THE EFFICACY OF DBS FOROCD IN THIS PERSON.WGS REVEALED THAT HE IS A HETEROZYGOTE FOR THE P.VAL66MET VARIANT IN BDNF, ENCODING A MEMBER OF THE NERVE GROWTH FACTOR FAMILY, AND WHICH HAS BEEN FOUND TO PREDISPOSE CARRIERS TO VARIOUS PSYCHIATRIC ILLNESSES. HE CARRIES THE P.GLU429ALA ALLELE IN METHYLENETETRAHYDROFOLATE REDUCTASE (MTHFR) AND THE P.ASP7ASN ALLELE IN CHAT, ENCODING CHOLINE O-ACETYLTRANSFERASE, WITH BOTH ALLELES HAVING BEEN SHOWN TO CONFER AN ELEVATED SUSCEPTIBILITY TO PSYCHOSES. WE HAVE FOUND THOUSANDS OF OTHER VARIANTS IN HIS GENOME, INCLUDING PHARMACOGENETIC AND COPY NUMBER VARIANTS. THIS INFORMATION HAS BEEN ARCHIVED AND OFFERED TO THIS PERSON ALONGSIDE THE CLINICAL SEQUENCING DATA, SO THAT HE AND OTHERS CAN RE-ANALYZE HIS GENOME FOR YEARS TO COME. TO OUR KNOWLEDGE, THIS IS THE FIRST STUDY IN THE CLINICAL NEUROSCIENCES THAT INTEGRATES DETAILED NEUROPSYCHIATRIC PHENOTYPING, DEEP BRAIN STIMULATION FOR OCD AND CLINICAL-GRADE WGS WITH MANAGEMENT OF GENETIC RESULTS IN THE MEDICAL TREATMENT OF ONE PERSON WITH SEVERE MENTAL ILLNESS. WE OFFER THIS AS AN EXAMPLE OF PRECISION MEDICINE IN NEUROPSYCHIATRY INCLUDING BRAIN-IMPLANTABLE DEVICES AND GENOMICS-GUIDED PREVENTIVE HEALTH CARE. REPORTED EVENT: A (B)(6) MAN¿S YBOCS SCORE STILL REMAINED IN THE 35-38 RANGE. FROM (B)(6) 2011, THE PATIENT¿S VOLTAGE WAS INCREASED BILATERALLY ON A MONTHLY BASIS IN INCREMENTS OF 0.2 VOLTS, WITH STEADY IMPROVEMENT WITH HIS OCD UNTIL HIS BATTERY STARTED TO LOSE CHARGE BY (B)(6) 2011. THIS CAUSED HIM CONSIDERABLE ANXIETY, PROMPTING HIM TO TURN OFF HIS BATTERY IN ORDER TO ¿SAVE BATTERY LIFE,¿ WHICH UNFORTUNATELY LED TO A COMPLETE RELAPSE TO HIS BASELINE STATE IN A 24 HOUR PERIOD, WHICH WAS REVERSED WHEN HE TURNED THE BATTERY BACK ON. THE BATTERY WAS SURGICALLY REPLACED. FURTHER INFORMATION HAS BEEN REQUESTED; A SUPPLEMENTAL REPORT WILL BE SUBMITTED IF ADDITIONAL INFORMATION IS RECEIVED.

    Devices

    Seq Brand Generic Product Code Manufacturer Model Lot UDI-DI
    636535 KINETRA STIMULATOR, ELECTRICAL, IMPLANTED, FOR PARKINSONIAN TREMOR MFR MEDTRONIC NEUROMODULATION 7428

    Patients

    Seq Age Sex Outcome Treatment
    1 00037 YR Required Intervention