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Frederick L. Hitti, Ashwin G. Ramayya, Brendan J. McShane, Andrew I. Yang, Kerry A. Vaughan and Gordon H. Baltuch

OBJECTIVE

Deep brain stimulation (DBS) is an effective treatment for several movement disorders, including Parkinson’s disease (PD). While this treatment has been available for decades, studies on long-term patient outcomes have been limited. Here, the authors examined survival and long-term outcomes of PD patients treated with DBS.

METHODS

The authors conducted a retrospective analysis using medical records of their patients to identify the first 400 consecutive patients who underwent DBS implantation at their institution from 1999 to 2007. The medical record was used to obtain baseline demographics and neurological status. The authors performed survival analyses using Kaplan-Meier estimation and multivariate regression using Cox proportional hazards modeling. Telephone surveys were used to determine long-term outcomes.

RESULTS

Demographics for the cohort of patients with PD (n = 320) were as follows: mean age of 61 years, 70% male, 27% of patients had at least 1 medical comorbidity (coronary artery disease, congestive heart failure, diabetes mellitus, atrial fibrillation, or deep vein thrombosis). Kaplan-Meier survival analysis on a subset of patients with at least 10 years of follow-up (n = 200) revealed a survival probability of 51% (mean age at death 73 years). Using multivariate regression, the authors found that age at implantation (HR 1.02, p = 0.01) and male sex (HR 1.42, p = 0.02) were predictive of reduced survival. Number of medical comorbidities was not significantly associated with survival (p > 0.5). Telephone surveys were completed by 40 surviving patients (mean age 55.1 ± 6.4 years, 72.5% male, 95% subthalamic nucleus DBS, mean follow-up 13.0 ± 1.7 years). Tremor responded best to DBS (72.5% of patients improved), while other motor symptoms remained stable. Ability to conduct activities of daily living (ADLs) remained stable (dressing, 78% of patients; running errands, 52.5% of patients) or worsened (preparing meals, 50% of patients). Patient satisfaction, however, remained high (92.5% happy with DBS, 95% would recommend DBS, and 75% felt it provided symptom control).

CONCLUSIONS

DBS for PD is associated with a 10-year survival rate of 51%. Survey data suggest that while DBS does not halt disease progression in PD, it provides durable symptomatic relief and allows many individuals to maintain ADLs over long-term follow-up greater than 10 years. Furthermore, patient satisfaction with DBS remains high at long-term follow-up.

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Andrew I. Yang, Brendan J. McShane, Frederick L. Hitti, Sukhmeet K. Sandhu, H. Isaac Chen and John Y. K. Lee

OBJECTIVE

First-line treatment for trigeminal neuralgia (TN) is pharmacological management using antiepileptic drugs (AEDs), e.g., carbamazepine (CBZ) and oxcarbazepine (OCBZ). Surgical intervention has been shown to be an effective and durable treatment for TN that is refractory to medical therapy. Despite the lack of evidence for efficacy in patients with TN, the authors hypothesized that patients with neuropathic facial pain are prescribed opioids at high rates, and that neurosurgical intervention may lead to a reduction in opioid use.

METHODS

This is a retrospective study of patients with facial pain seen by a single neurosurgeon. All patients completed a survey on pain medications, medical comorbidities, prior interventions for facial pain, and a validated pain outcome tool (the Penn Facial Pain Scale). Patients subsequently undergoing neurosurgical intervention completed a survey at the 1-month follow-up in the office, in addition to telephone interviews using a standardized script between 1 and 6 years after intervention. Univariate and multivariate logistic regression were used to predict opioid use.

RESULTS

The study cohort consisted of 309 patients (70% Burchiel type 1 TN [TN1], 18% Burchiel type 2 [TN2], 6% atypical facial pain [AFP], and 6% TN secondary to multiple sclerosis [TN-MS]). At initial presentation, 20% of patients were taking opioids. Of these patients, 55% were receiving concurrent opioid therapy with CBZ/OCBZ, and 84% were receiving concurrent therapy with at least one type of AED. Facial pain diagnosis (for diagnoses other than TN1, odds ratio [OR] 2.5, p = 0.01) and facial pain intensity at its worst (for each unit increase, OR 1.4, p = 0.005) were predictors of opioid use at baseline. Neurosurgical intervention led to a reduction in opioid use to 8% at long-term follow-up (p < 0.01, Fisher’s exact test; n = 154). Diagnosis (for diagnoses other than TN1, OR 4.7, p = 0.002) and postintervention reduction in pain at its worst (for each unit reduction, OR 0.8, p < 10−3) were predictors of opioid use at long-term follow-up. On subgroup analysis, patients with TN1 demonstrated a decrease in opioid use to 5% at long-term follow-up (p < 0.05, Fisher’s exact test), whereas patients with non-TN1 facial pain did not. In the nonsurgical group, there was no statistically significant decrease in opioid use at long-term follow-up (n = 81).

CONCLUSIONS

In spite of its high potential for abuse, opioid use, mostly as an adjunct to AEDs, is prevalent in patients with facial pain. Opportunities to curb opioid use in TN1 include earlier neurosurgical intervention.

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Frederick L. Hitti, Kerry A. Vaughan, Ashwin G. Ramayya, Brendan J. McShane and Gordon H. Baltuch

OBJECTIVE

Deep brain stimulation (DBS) has revolutionized the treatment of neurological disease, but its therapeutic efficacy is limited by the lifetime of the implantable pulse generator (IPG) batteries. At the end of the battery life, IPG replacement surgery is required. New IPGs with rechargeable batteries (RC-IPGs) have recently been introduced and allow for decreased reoperation rates for IPG replacements. The authors aimed to examine the merits and limitations of these devices.

METHODS

The authors reviewed the medical records of patients who underwent DBS implantation at their institution. RC-IPGs were placed either during initial DBS implantation or during an IPG change. A cost analysis was performed that compared RC-IPGs with standard IPGs, and telephone patient surveys were conducted to assess patient satisfaction.

RESULTS

The authors identified 206 consecutive patients from 2011 to 2016 who underwent RC-IPG placement (mean age 61 years; 67 women, 33%). Parkinson’s disease was the most common indication for DBS (n = 144, 70%), followed by essential tremor (n = 41, 20%), dystonia (n = 13, 6%), depression (n = 5, 2%), multiple sclerosis tremor (n = 2, 1%), and epilepsy (n = 1, 0.5%). DBS leads were typically placed bilaterally (n = 192, 93%) and targeted the subthalamic nucleus (n = 136, 66%), ventral intermediate nucleus of the thalamus (n = 43, 21%), internal globus pallidus (n = 21, 10%), ventral striatum (n = 5, 2%), or anterior nucleus of the thalamus (n = 1, 0.5%). RC-IPGs were inserted at initial DBS implantation in 123 patients (60%), while 83 patients (40%) were converted to RC-IPGs during an IPG replacement surgery. The authors found that RC-IPG implantation resulted in $60,900 of cost savings over the course of 9 years. Furthermore, patient satisfaction was high with RC-IPG implantation. Overall, 87.3% of patients who responded to the survey were satisfied with their device, and only 6.7% found the rechargeable component difficult to use. In patients who were switched from a standard IPG to RC-IPG, the majority who responded (70.3%) preferred the rechargeable IPG.

CONCLUSIONS

RC-IPGs can provide DBS patients with long-term therapeutic benefit while minimizing the need for battery replacement surgery. The authors have implanted rechargeable stimulators in 206 patients undergoing DBS surgery, and here they demonstrate the cost-effectiveness and high patient satisfaction associated with this procedure.

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Kendall H. Lee, Frederick L. Hitti, Mark H. Shalinsky, Uhnoh Kim, James C. Leiter and David W. Roberts

Object

The mechanism of action whereby high-frequency stimulation (HFS) in the thalamus ameliorates tremor and epilepsy is unknown. The authors studied the effects of HFS on thalamocortical relay neurons in a ferret in vitro slice preparation to test the hypothesis that HFS abolishes synchronized oscillations by neurotransmitter release.

Methods

Intracellular and extracellular electrophysiological recordings were made in thalamic slices. The neurons in the thalamic slice spontaneously generated spindle oscillations, and treatment with picrotoxin, a γ-aminobutyric acid A receptor antagonist, resulted in 3- to 4-Hz absence seizurelike activity. High-frequency stimulation (stimulation parameters: 10–1000-µA amplitude; 100-µsec pulse width; 100-Hz frequency; 1–60 seconds) was applied using a concentric bipolar stimulating electrode placed adjacent to the recording electrodes.

High-frequency stimulation within the thalamus generated inhibitory and excitatory postsynaptic potentials, membrane depolarization, an increase in action potential firing during the stimulation period, and abolished the spindle oscillations in the thalamocortical relay neurons. High-frequency stimulation applied to 20-µM picrotoxin-treated slices eliminated the 3- to 4-Hz absence seizurelike activity.

Conclusions

High-frequency stimulation eliminates spontaneous spindle oscillations and picrotoxin-induced absence seizurelike activity in thalamic slices by synaptic neurotransmitter release; thus, HFS may abolish synchronous oscillatory activities such as those that generate tremor and seizures. Paradoxically, HFS, which is excitatory, and surgical lesions of the ventrointermedius thalamus, which are presumably inhibitory, both suppress tremors. This paradox is resolved by recognizing that HFS-mediated neurotransmitter release and thalamic surgery both disrupt the circuit generating tremor or seizure, albeit by different mechanisms.