Dementia after DBS Surgery: A Case Report and Literature Review
Parkinsons Dis. 2011; 2011: 679283.
Published online 2011 November 29. doi: 10.4061/2011/679283
I. Rektorova, 1, 2 * Z. Hummelova, 1 and M. Balaz 1, 2
We report the case history of a 75-year-old woman with Parkinson's disease who developed severe cognitive problems after deep brain stimulation (DBS) of the bilateral subthalamic nuclei (STN). After a brief cognitive improvement, the patient gradually deteriorated until she developed full-blown dementia. We discuss the case with respect to the cognitive effects of STN DBS and the possible risk factors of dementia after STN DBS surgery.
2. Case History
A 61-year-old woman was diagnosed with PD in 1991. She had no family history of PD and she had not been chronically treated for any other medical condition. She worked as a high school teacher until the age of 65.
No complications were observed at the time of surgery; the patient remained conscious, alert, and cooperative during all stages of the procedure. Nevertheless, on the day after the electrode implantation, a transient somnolence, disorientation in time and space, and retrograde amnesia occurred. This acute confusion regressed within 4 days. The electrode cables were internalized, and a neurostimulation device (Kinetra, Medtronic Inc., Minneapolis, USA) was implanted. The patient was released from the hospital. She was rehospitalized one month later in order to start the stimulation.
In January 2006, a neuropsychological examination was performed with the stimulation off while the patient was on stable dopaminergic medication. It revealed a moderately intense organic psychosyndrome and a marked dysexecutive syndrome with a major impact on other cognitive functions and instrumental activities of daily living. It manifested symptomatically by decreased psychomotor speed, flexibility, spontaneity, and concentration, as well as attention deficits and disinhibition (see Figure 1 for the intersecting pentagons drawing from the Mini-Mental State Examination (MMSE, )). Mild memory impairment was also identified, affecting primarily recent episodic and semantic memory. Visuospatial deficits, dyscalculia, and deficits in time orientation were also reported, and the patient became negativistic and dysphoric. Her MMSE score was 14 points and the Montgomery-Asberg Depression Rating Scale (MADRS) score was 24 . We performed brain MRI and FLAIR sequences to verify the electrode location and to rule out possible adverse effects of implantation. The electrode location was correct; however, mild oedema and bleeding were found in the anterior limb of the left internal capsule, spreading to the putamen and caudate head (see Figure 2(a)).
During the summer of 2006, the patient's medical condition again started to gradually deteriorate, with episodes of freezing of gait and postural instability, visual hallucinations, and delusions. The behavioural disturbances were worse in the morning. The patient experienced no tremor. Sometimes she had very mild dyskinesias on the left side, but no motor fluctuations were present. She left the house and got lost repeatedly, and she became partially dependent on the caregiver (her husband). Quetiapine was started at that time with a dose titration up to 75mg per day; this was later exchanged for clozapine in low doses (50mg per day). All other medications except L-dopa (550mg/day) and citalopram (20mg/day) were withdrawn. Cognitive testing in March 2007 confirmed the cognitive decline, with a Mattis Dementia Rating Scale score of 116 points and an IQ score measured at 90. In addition to dysexecutive syndrome, memory functions, and praxis, visuoconstructive, visuospatial, and other cognitive functions were impaired, including writing and picture drawing.
In 2008, full-blown dementia was reported, which progressed over time. Memantin (20mg per day) was introduced, but no visible effect on slowing the dementia course was detected. In December 2008, a marked overall brain atrophy was depicted in brain MRI, including both hippocampi. White matter hyperintensities along the electrode trajectories (possible gliosis) were also visible (see Figure 2(c)). In 2009, the MMSE score was 19, and according to the 7-min subtests , orientation in time score was 74, enhanced cued memory score was 8, the clock test score was 1, and semantic verbal fluency was 5. In February 2010, the stimulation battery was changed, with the last stimulation parameters being as follows: amplitude 3.6V and 3.8V for the left and right sides, respectively, stimulation frequency 130Hz, pulse width 90μsec. The MMSE was 14. The patient suffered from hallucinations, delusions, and postural instability with occasional falls. She had severe aphasia and dysarthria with telegraphic slurred speech and moderately severe motor and ideomotor apraxia. She became incontinent, and fully dependent on her husband. She died in April 2010. The probable cause of death was pneumonia. No brain biopsy was performed.
Another interesting issue that has to be taken into consideration relates to possible gliosis along the electrode trajectories. It has been shown by others  that DBS electrodes may cause a giant cell reaction or gliosis around them when implanted in the brains of patients with PD. This reaction is present from 3 months to at least 31 months onwards after implantation, and may possibly represent a response to the polyurethane component of the electrodes' surface coat. The accumulation of inflammatory tissue occurs predominantly around the electrode sheath rather than tip, and it is conceivable that on the whole it plays only a small role in maintaining benefit or causing side effects of DBS .
Finally, we indeed cannot exclude a possibility that the ICH as an adverse event of the STN implantation might not only have caused an acute cognitive and behavioural impairment after the procedure but might also have accelerated the development of dementia in our patient, probably as a result of collapsed brain reserve and disturbed compensatory mechanisms caused by the electrode implantation and IHC. Age was probably the major contributor and risk factor for the intracranial bleeding, postoperative confusion, and later dementia development [26, 40, 41].
Despite many unresolved questions, this has taught us not to include PD patients above 70 years of age for the DBS surgery. In addition, the length of PD duration should also be taken into consideration, and the question remains as to what the best time for considering DBS in PD would be. Further research should focus on potential biological markers such as specific brain imaging techniques and cerebrospinal fluid examination that would better predict the disease prognosis and that might help to better select good candidates for DBS surgery in PD patients.
Specific Edema Citings in DBS Adverse Event Reports filed to the FDA between 2010 and 2013
Reportable event: one (b)(6) male presented to the emergency room complaining of a headache (b)(6) following gpi dbs implantation. Edema was found at the tip of the lead. The pt was given steroids for (b)(6) for this to resolve.
Reportable event: one (b)(6) left-handed male with a history of idiopathic parkinson's disease (pd) was admitted for placement of a right-sided stn electrode. Immediate post-operative ct head scans revealed minimal pneumocephalus with no parenchymal hemorrhage. The pt was discharged on postoperative day 2 with a normal exam. His second stage of surgery for implantation of the ipg was scheduled for a later date. Two weeks after discharge, the pt presented to the emergency room with a history of a single generalized convulsion followed by a brief loss of consciousness. On exam he was orientated and had no focal deficits. A ct brain scan revealed a large hypodense area (3cmx4cmx3cm) centered around the left dbs electrode primarily in the subcortical region and centrum semiovale that did not enhance on contrast administration. No local or systemic signs or symptoms of infection were present. He did not have any further episodes of seizure and was discharged home on anti-convulsant medication and a short course of oral steroids. A f/u ct scan after 1 week showed resolution of the edema. The pt was not given antibiotics.
It was reported that the patient was implanted with an activa rc on (b)(6) 2011 and everything was ok. The patient came to a consultation in (b)(6) 2011 / (b)(6) 2011 because she didn't feel well. The stimulator and impedances were ok, but the doctor saw an edema around the two electrodes and had a suspicion of infection. The doctor stopped stimulation, but could not confirm an infection. The doctor started a treatment with medrol and the patient seemed to improve, but the activa rc was not restarted.
Report number not recorded by accident.
Event: following the second stage of the stn-dbs surgery during which the stimulator was implanted and during which the pt had mechanical ventilation, the pt's trachea was extubated and the pt was moved to the icu. On the fifth post-operative day, 40 mg of enoxaparin was administered to prevent deep vein thrombosis. The pt became unresponsive within a few hours of administration. The pt was reintubated and taken for a ct scan which revealed an intracerebral hematoma in the left basal ganglion and left fronto-parietal region with midline shift and perilesional edema. Prothrombin time and activated partial thromboplastin time were prolonged with a normal platelet count. Enoxaparin was discontinued and six units of fresh frozen plasma were transfused, while mechanical ventilation was continued. The pt's coagulation status returned to normal within the next four days, and there was an improvement in neurological status. The hematoma had resolved and was not expanding so no evacuation was performed. The pt then developed ventilator-associated pneumonia and sepsis due to methicillin-resistant staphylococcus aureus on post-operative day 25.
Reportable event: Two patients experienced seizures that were considered surgery related, dbs-specific. One pt experienced visual neglect from edema that was considered surgery related, dbs-specific.
Literature: chhabra v, sung e, mewes k, bakay ra, abosch a, gross re. Safety of magnetic resonance imaging of deep brain stimulator systems: a serial imaging and clinical retrospective study. J neurosurg. 2010;112(3):497-502. Summary: this study aimed to examine the safety of mr imaging in 64 pts who underwent staged bilateral implantations of dbs electrodes at emory university hospital between (b)(6) 1997 and (b)(6) 2006 for parkinson disease, tremor and dystonia. Each pt underwent three separate mr imaging sessions subsequent to dbs placement. The first was performed within 24 hrs after the first dbs placement, the second occurred prior to the contralateral second dbs placement which was an average of 19. 4 months later, and the third was within 24 hrs after the second dbs placement. F/u was conducted to examine adverse events related either to mr imaging or to dbs-induced injury. Reportable events: one pt experienced encephalomalacia surrounding the first dbs lead secondary to gliosis that was noted on long-term mr imaging sequences. This pattern was consistent with insertional injury. The pt had an ablative procedure performed by intentionally subjecting a dbs lead to radiofrequency currents prior to its removal. Seven pts experienced edema. The edema appeared on the mr images taken immediately after lead placement, either on the first set of mr images or the images obtained immediately after the second lead insertion, but never on the second set of images that was performed months after the first insertion. The edema surrounded the acutely implanted lead and never was seen surrounding the chronically implanted lead. It was concluded that the edema resulted solely from micro-electrode and/or dbs-induced injury. Six pts experienced focal intraparenchymal hemorrhage. This was seen either on the first or third mr imaging sessions, but never on the second. Four pts experienced intra-ventricular hemorrhage. This was seen either on the first or third mr imaging sessions, but never on the second. One pt experienced infarct that was noted 2 days after the second dbs placement and confirmed on the repeated mr imaging studies obtained 2 weeks thereafter. One pt experienced sulcal subarachnoid blood. Seven pts experienced encephalomalacia surrounding the first dbs lead secondary to gliosis that was noted on long-term mr imaging sequences. This pattern was consistent with insertional injury. Most of these cases of encephalomalacia occurred after documented intraparenchymal hemorrhage or edema on immediate mr imaging following the first or second lead placement. No events were attributed to effects of mr imaging.
Reportable event: one pt experienced a small delayed superficial cortical hemorrhage with mild postoperative dysarthria which resolved within 1 month of surgery and was thought to be unrelated to the bleed, and probably related to immediate postoperative edema around the electrode tip, given that this dysarthria could be reproduced by high-voltage stimulation on long-term f/u. There was no other hemorrhagic complication in this series of patients.
The hcp noted an area of hypodensity in a pt treated with deep brain stimulation. He was in the process of evaluating the event as a possible stroke.
(According to the FDA, this is Ed’s adverse event report as filed by Medtronic.)
One week after implant, the leads were removed due to an allergic reaction. The patient developed an infection and edema from the bur hole down to the brain. As of (b) (6) 2010, the patient was in the intensive care unit. Additional information has been requested, a follow-up report will be sent if additional information becomes available.
Event: The patient, a (b)(6) male with parkinson's disease (pd), had been operated with left-sided vim dbs 7 years before. Due to suboptimal treatment results and disease progression, it was decided to replace the electrode with bilateral electrodes in the zona incerta. The old electrode, which was found to be broken, was removed 2 days before the procedure to facilitate mri. A ct on postoperative day 5 demonstrated an edema around the right electrode, with progression on the following day and a contrast-enhanced area around the edema. Furthermore, similar changes but to a lesser extent were noted around the left electrode. These changes were interpreted as cerebritis with developing abscess. The patient was initially treated with intravenous (vancocin and meronem) and later with oral antibiotics for 8 weeks. Twenty days after the operation, ct demonstrated apparent amelioration of intracerebral changes and recovery of the patient. An mri did however reveal remaining edema on the right side, especially around the tip of the electrode. For this reason, the right electrode was removed. Bacterial culture from the electrode demonstrated growth of (b)(6). Eleven weeks after the initial operation and 3 weeks after discontinuation of antibiotic treatment, the patient presented with headache, vertigo and later rupture of the cranial incision above the entry of the electrode with pus. The patient recovered without any permanent sequelae.
[IS SHIFTING DUE TO UNDETECTED EDEMA?]
Reportable event: some pts appeared to have a significant shift in the location of the electrodes between the immediate and 6-month post-operative ct. The shift moved in the ventral direction. The shift was felt to be partly due to csf leakage during the operation. No pt treatment or outcome was reported.
Here's the list of adverse events citing 'infection'...some of which could be 'edema' misdiagnosed.
You make the call…Infection or Edema…or both?
Reportable event: one patient experienced an infection of the intracranial lead: the control mri showed a signal change in both t1 and t2 sequences along the lead. Cultures were negative; the patient underwent the removal of the infected electrode and was started on an antibiotic therapy. The pt was successfully reimplanted 6 months later after resolution of the infection. This complication required a longer in-hospital stay for the patient however, the patient did not show significant comorbidity.
It was reported the patient has a dbs system for treatment of dystonia. The device was originally placed in (b) (6), 2007. The patient has had great benefit but has had the right side device removed 4 times due to infection. No other information was provided. This report is submitted for infection event 1 of 4.
It was reported the pt presented to the emergency room with severe eye/facial pain and swelling on the left side. There was also redness and swelling a the coronal incision site. A computed tomography (ct) scan of the head and lumbar puncture was performed and the results were "negative. " it was determined the pt had cellulitis and treatment was started with vancomycin. The pt improved with the vancomycin treatment, and the pt was switched to bactrim in preparation for discharge. Later the pt awoke from sleep with swollen eyes and a severe, throbbing headache. The pt also had retro-orbital pressure, which was new. The pt was put on iv vancomycin and ceftazidime. A magnetic resonance imaging (mri) was performed, and the result showed no intracranial abscess or infection. The pt was to be discharged on iv antibiotics.
It was reported that the patient developed an infection their right lead, and the lead was removed. There was no outcome reported from the surgery. No further follow up is possible.
It was reported that the patient underwent an implant for parkinson's. After he received the surgery he developed an infection and was oozing from his head. It was reported that the patient was still alive, but very ill. Additional information has been requested, but was not available as of the date of this report.
Reportable event: the authors reported that one pt had a hardware infection in the first 3 months after surgery. [Vague] This complication was related to technical factors [Vague], including externalization of electrodes. The hardware was replaced without complication and with continuing clinical benefit. The source literature did not specify which device model was used. See literature article with mfr report# 3007566237-2011-07025. Manufacturer Narrative (b)(4). It was not possible to ascertain specific device info from the article or to match the events reported with previously reported events. At this time no add'l info was available, add'l info regarding the pt and the device has been requested.
Reportable event: during the first 6 months after the operation, two patients had their stimulation electrodes removed due to an infection and one pt committed suicide.
Reportable event: a (b)(6) female, pt, with cerebellar tremor, cerebellar degeneration, and peptic ulcer disease experienced a deep infection with purulent drainage in the right frontal burr hole incision 22 days after implant. A culture came back positive for (b)(6) and (b)(6). The pt underwent incision and debridement with right lead removal and was treated with intravenous antibiotics. Antibiotics were continued for at least 6 weeks. A weekly f/u was undertaken with examination of the wound until it was completely healed.
Reportable events: One male pt, (b)(6) at the time of initial implantation surgery, developed a 'hardware' infection. One male pt, (b)(6) at the time of initial implantation, developed a 'hardware' infection [Vague]. Manufacturer Narrative (b)(4). It was not possible to ascertain specific device info from the article or to match the events reported with previously reported events. At this time no add'l info was available, add'l info regarding the pt, event, interventions and outcome has been requested.
Reportable events: one pt experienced wound infection [Vauge]. One pt experienced a stimulation induced hemiballism. One pt experienced an asymptomatic intracerebral hemorrhage. Manufacturer Narrative (b)(4). It was not possible to ascertain specific device info from the article or to match the events reported with previously reported events. At this time no add'l info was available, add'l info regarding the pt, event, interventions and outcome has been requested.
Reportable event: one patient experienced a (b)(6) adverse event, their leads became infected. The infected device components were removed and re-implanted following an appropriate course of intravenous antibiotics. Manufacturer Narrative (b)(4). It was not possible to ascertain specific device information from the article or to match the events reported with previously reported events.
[Note how the fact that the one patient being on immunosuppressants causes us to discount the other patient’s status].
Reportable event: the authors report two infections of the implanted devices; one patient was under immunosuppressant therapy following a renal transplant. Manufacturer Narrative (b)(4). It was not possible to ascertain specific device information from the article or to match the events reported with previously reported events.
[Ridiculous…I believe this was filed by MedTronic staff.]
Rec'd info, the physician had a pt with an infection at one time. He now uses vancomycin for protection. No further info provided.
Reportable events: the complication rate was low with no mortality or hemorrhages. It was reported that one pt had a minor complication related to surgery; the pt experienced acute chest pain, probably attributed to cardiac ischemia and the dbs procedure was discontinued prior to implanting the electrodes. Two months later, the pt was operated for unilateral vim-dbs. One pt had a minor complication related to surgery; the pt experienced discomfort caused by tight dbs wires in the neck region and was re-operated after 7 months. There were no infections related to lead implantation, but two cases developed a mild local infection following a change of battery 5 years after dbs implantation. There were several transient neurological side effects; apraxia of eyelid opening (n=2), anxiety and depression (n=3) and hypomania (n=3). There were 4 cases of permanent cognitive impairment. Manufacturer Narrative (b)(4). It was not possible to ascertain specific device information from the article or to match the events reported with previously reported events. It is also possible several events occurred in one pt. At this time, no additional information was available, additional information regarding the pt, event, interventions and outcome has been requested.
Reportable event: fourteen of the 44 pts had a total of 18 revisions. Two pts that had a new lead put in place because of dislocation [EDEMA?], nine pts had a new lead put in place because of lead fracture, with four of these pts undergoing a second revision, again lead replacement. In three cases there was a problem with the connection, with pain due to local current leakage, requiring opening of the connection and cleaning it. There were two instances of infection, one at the level of the lead insert during the trial period, and one later after implantation at the level of the connector due to a small skin defect. Both infections were resolved with short-term antibiotic treatment. Manufacturer Narrative (b)(4). It was not possible to ascertain specific device information from the article or to match the events reported with previously reported events. At this time no additional information was available, additional information regarding the pt, event, interventions and outcome has been requested.
Reportable event: one yopd patient experienced an infection. See literature article with mfr report# 3007566237-2011-02256. It was not possible to ascertain specific device information from the article or to match the events reported with previously reported events. The patient information provided in section a is the average for all the patients within the yopd group. At this time, no additional information was available, additional information regarding the patient, event and outcome has been requested.
The ins and extension were removed due to infection. Details were not provided. Further information is being requested at this time
The deep brain stimulator system was infected with staphylococcus aureus. The devices were explanted and the patient was treated with antibiotics. The patient was hospitalized associated with the infection. Additional information has been requested. A follow-up report will be submitted if additional information becomes available.
[Props for the Medtronic rep]
Received information there was an infection at the lead/extension area. Medtronic representative was inquiring about cleaning the area with either betadine or hydrogen peroxide. No other information was provided. Additional information has been requested and if received a follow report will be sent.
Reportable event: this report is for one pt who developed postoperative infection requiring dbs lead removal, intravenous antibiotics, and subsequent reimplantation. The source literature did not specify which device models were used.
It was reported that the pt felt pain in the lead, and the health care professional (hcp) found signs of lead "exposion" and believed there might have been infection. The lead and extension were explanted. It was later reported that the pt subsequently went to the hosp, and the hcp found no swelling, ulceration, or lead "exposion". No infection was found. It was noted that the pt felt pain behind the ear. The hcp was "observing" the pt. Manufacturer Narrative (b)(4): the lead and extension have been returned to the mfr for analysis. A f/u report will be sent when the analysis is complete.
Reportable event: one patient experienced an infection of the intracranial lead: the control mri showed a signal change in both t1 and t2 sequences along the lead. Cultures were positive for (b)(6); the patient underwent the removal of the infected electrode and was started on an antibiotic therapy, but refused to undergo a second surgery. This complication required a longer in-hospital stay for the patient however the patient did not show significant comorbidity.
Reportable event: one pt experienced an aspiration pneumonia 1 week after surgery while still in hospital. This resulted in severe lung infection and respiratory failure, requiring admission to the intensive care unit, tracheostomy, and wide-range antibiotic therapy. Despite maximal treatment, the pt eventually died a few weeks later. He was one of the oldest patients in our series (70 years at surgery) and presented with severe pd. Dysphagia was present preoperatively and did not improve after surgery. See literature article with mfr report #3007566237-2010-08991.
It was reported patient had deep brain stimulation (dbs) system in 2004 and changed to implantable pulse generator (ipg) in (b)(6) 2008. According to patient, "the incision on the left side head occurred purulence about a month ago". When he returned to the hospital for programming, physician identified it as infected. After communicating between patient and company, physician decided to remove the infected electrode. The surgery was planned for (b)(6) 2010. The lead was explanted. At the time of this report, no further details were reported. Add'l info was requested and will be provided when it becomes available.
Event: the frequency of the 300 adverse events were as follows: mental status decline 53, other (unspecified) 43, gait problem 21, other motor problem 20, seizure 16, ich (symptomatic) 16, lead misplacement 15, speech-aphasia 13, speech-dysarthria 11, subdural/other bleed 11, mania/hypomania 8, infection, deep (hardware removal) 7, air embolus 6, speech-hypophonia 6, depression 6, infection, deep (revision, iv antibiotics) 5, swallow problem 5, anxiety 5, incontinence 4, visual problem 4, infection, superficial (oral antibiotics) 4, hardware malfunction (other) 4, death 2, hardware malfunction (fracture) 2, hydrocephalus 2, neurological deficit (other) 2, stroke 2, scalp erosion 2, suicidal ideation 2, ipg seroma 1, other sensory problem 1 and psychogenic disorder 1. See attached literature article.
The only complication with this group presented with an infection of a surgical wound. Both inability and disability improved, and remained stable after two yrs.
[Ed’s case…see how it looks like infection is the causal agent?...even though his doctor’s meticulously put in his record that there was no sign of infection? Would Medtronic file this way on one of your patients if they filed this way on Ed?...assuming the FDA is correct and this is Ed’s filing].
One week after implant, the leads were removed due to an allergic reaction. The patient developed an infection and edema from the bur hole down to the brain. As of (b) (6) 2010, the patient was in the intensive care unit. Additional information has been requested, a follow-up report will be sent if additional information becomes available. See also manufacturer's report # 3007566237201003885
Event: one pt with pd and bilateral implants suffered a postoperative infection. Three days after surgery he developed fever, elevated c-reactive protein, mild intermittent confusion and a discrete left-sided hemiparesis. Signs of inflammation were seen along the right cerebral electrode. The electrode was removed, and samples for bacteriological culture were collected. The cultures were negative and the pt was treated presumptively with antibiotics, and had recovered fully within 1 month. However, after 3 months, the scar over the left electrode became purulent. The second electrode was removed and cultures demonstrated growth of coagulase-negative staphylococcus aureus, enterobacter aerogenes and alpha-hemolytic streptococcus. This pt did not suffer any permanent sequelae.
Event: two pd pts experienced infection/hardware removal resulting in three er visits. No further info was provided. See literature article with mfr report# 3007566237-2010-03105.
Event: five pd pts experienced infection resulting in seven er visits. No further info was provided. See literature article with mfr report #3007566237201003105.
Event: there were five events of infection (lead/ipg/wound). No further information was provided. See literature article with mfr report #3007566237201003026.
Reportable event: one pt presented with an infection of the scalp. The issue resolved after the system was explanted. The event was noted to occur before the first pre-protocol f/u visit. See literature article attached to mfr report# 3007566237201001765.
Reportable event: one pt had a lead removed due to infection. No pt outcome was reported.
Reported event: one pt experienced a postoperative infection requiring removal of all the hardware. The pt underwent re-insertion on the same side. See literature article mfr report # 3007566237201001699.