Chronic itch induced by thalamic deep brain stimulation: a case for a central itch centre.

BACKGROUND: Central itch syndrome has been previously described in conditions such as stroke. The neurophysiology of central itch syndrome has been investigated in non-human primates but remains incompletely understood. METHODS: We report an observational study of a rare case of severe central itch following thalamic deep brain stimulation and postulate the location of the central itch centre in humans. RESULTS: The patient was a 47-year-old female, with congenital spinal malformations, multiple previous corrective spinal surgeries and a 30-year history of refractory neuropathic pain in her back and inferior limbs. Following multidisciplinary pain assessment and recommendation, she was referred for spinal cord stimulation, but the procedure failed technically due to scarring related to her multiple previous spinal surgeries. She was therefore referred to our centre and underwent bilateral deep brain stimulation (DBS) of the ventral posterolateral nucleus of the thalamus for management of her chronic pain. Four weeks after switching on the stimulation, the patient reported significant improvement in her pain but developed a full body progressive itch which was then complicated with a rash. Common causes of skin eczema were ruled out by multiple formal dermatological evaluation. A trial of unilateral "off stimulation" was performed showing improvement of the itchy rash. Standard and normalized brain atlases were used to localize the active stimulating contact within the thalamus at a location we postulate as the central itch centre. CONCLUSIONS: Precise stereotactic imaging points to the lateral portion of the ventral posterolateral and posteroinferior nuclei of the thalamus as critical in the neurophysiology of itch in humans.

Long-Term Efficacy of Constant Current Deep Brain Stimulation in Essential Tremor.

OBJECTIVES: Ventralis intermedius deep brain stimulation is an established intervention for medication-refractory essential tremor. Newer constant current stimulation technology offers theoretical advantage over the traditional constant voltage systems in terms of delivering a more biologically stable therapy. There are no previous reports on the outcomes of constant current deep brain stimulation in the treatment of essential tremor. This study aimed to evaluate the long-term efficacy of ventralis intermedius constant current deep brain stimulation in patients diagnosed with essential tremor. MATERIALS AND METHODS: Essential tremor patients implanted with constant current deep brain stimulation for a minimum of three years were evaluated. Clinical outcomes were assessed using the Fahn-Tolosa-Marin tremor rating scale at baseline and postoperatively at the time of evaluation. The quality of life in the patients was assessed using the Quality of Life in Essential Tremor questionnaire. RESULTS: Ten patients were evaluated with a median age at evaluation of 74 years (range 66-79) and a mean follow up time of 49.7 (range 36-78) months since starting stimulation. Constant current ventralis intermedius deep brain stimulation was well tolerated and effective in all patients with a mean score improvement from 50.7 ± 5.9 to 17.4 ± 5.7 (p = 0.0020) in the total Fahn-Tolosa-Marin rating scale score (65.6%). Furthermore, the total combined mean Quality of Life in Essential Tremor score was improved from 56.2 ± 4.9 to 16.8 ± 3.5 (p value = 0.0059) (70.1%). CONCLUSION: This report shows that long-term constant current ventralis intermedius deep brain stimulation is a safe and effective intervention for essential tremor patients.

The aperiodic exponent of subthalamic field potentials reflects excitation/inhibition balance in Parkinsonism.

Periodic features of neural time-series data, such as local field potentials (LFPs), are often quantified using power spectra. While the aperiodic exponent of spectra is typically disregarded, it is nevertheless modulated in a physiologically relevant manner and was recently hypothesised to reflect excitation/inhibition (E/I) balance in neuronal populations. Here, we used a cross-species in vivo electrophysiological approach to test the E/I hypothesis in the context of experimental and idiopathic Parkinsonism. We demonstrate in dopamine-depleted rats that aperiodic exponents and power at 30-100 Hz in subthalamic nucleus (STN) LFPs reflect defined changes in basal ganglia network activity; higher aperiodic exponents tally with lower levels of STN neuron firing and a balance tipped towards inhibition. Using STN-LFPs recorded from awake Parkinson's patients, we show that higher exponents accompany dopaminergic medication and deep brain stimulation (DBS) of STN, consistent with untreated Parkinson's manifesting as reduced inhibition and hyperactivity of STN. These results suggest that the aperiodic exponent of STN-LFPs in Parkinsonism reflects E/I balance and might be a candidate biomarker for adaptive DBS.

Shielded battery syndrome: a new hardware complication of deep brain stimulation.

BACKGROUND: Deep brain stimulation hardware is constantly advancing. The last few years have seen the introduction of rechargeable cell technology into the implanted pulse generator design, allowing for longer battery life and fewer replacement operations. The Medtronic® system requires an additional pocket adaptor when revising a non-rechargeable battery such as their Kinetra® to their rechargeable Activa® RC. This additional hardware item can, if it migrates superficially, become an impediment to the recharging of the battery and negate the intended technological advance. AIM: To report the emergence of the 'shielded battery syndrome', which has not been previously described. METHODS: We reviewed our deep brain stimulation database to identify cases of recharging difficulties reported by patients with Activa RC implanted pulse generators. RESULTS: Two cases of shielded battery syndrome were identified. The first required surgery to reposition the adaptor to the deep aspect of the subcutaneous pocket. In the second case, it was possible to perform external manual manipulation to restore the adaptor to its original position deep to the battery. CONCLUSIONS: We describe strategies to minimise the occurrence of the shielded battery syndrome and advise vigilance in all patients who experience difficulty with recharging after replacement surgery of this type for the implanted pulse generator.

One year double blind study of high vs low frequency subcallosal cingulate stimulation for depression.

Subcallosal Brodmann's Area 25 (Cg25) Deep Brain Stimulation (DBS) is a new promising therapy for treatment resistant major depressive disorder (TR-MDD). While different DBS stimulating parameters may have an impact on the efficacy and safety of the therapy, there is no data to support a protocol for optimal stimulation parameters for depression. Here we present a prospective multi-center double-blind randomized crossed-over 13-month study that evaluated the effects of High (130 Hz) vs Low (20 Hz) frequency Cg25 stimulation for nine patients with TR-MDD. Four out of nine patients achieved response criteria (≥40% reduction of symptom score) compared to mean baseline values at the end of the study. The mean percent change of MADRS score showed a similar improvement in the high and low frequency stimulation groups after 6 months of stimulation (-15.4 ± 21.1 and -14.7 ± 21.1 respectively). The mean effect at the end of the second period (6 months after cross-over) was higher than the first period (first 6 months of stimulation) in all patients (-23.4 ± 19.9 (n = 6 periods) and -13.0 ± 22 (n = 9 periods) respectively). At the end of the second period, the mean percent change of the MADRS scores improved more in the high than low frequency groups (-31.3 ± 19.3 (n = 4 patients) and -7.7 ± 10.9 (n = 2 patients) respectively). Given the small numbers, detailed statistical analysis is challenging. Nonetheless the results of this study suggest that long term high frequency stimulation might confer the best results. Larger scale, randomized double blind trials are needed in order to evaluate the most effective stimulation parameters.

Verbal Memory Decline following DBS for Parkinson's Disease: Structural Volumetric MRI Relationships.

BACKGROUND: Parkinson's disease is a chronic degenerative movement disorder. The mainstay of treatment is medical. In certain patients Deep Brain Stimulation (DBS) may be offered. However, DBS has been associated with post-operative neuropsychology changes, especially in verbal memory. OBJECTIVES: Firstly, to determine if pre-surgical thalamic and hippocampal volumes were related to verbal memory changes following DBS. Secondly, to determine if clinical factors such as age, duration of symptoms or motor severity (UPDRS Part III score) were related to verbal memory changes. METHODS: A consecutive group of 40 patients undergoing bilateral Subthalamic Nucleus (STN)-DBS for PD were selected. Brain MRI data was acquired, pre-processed and structural volumetric data was extracted using FSL. Verbal memory test scores for pre- and post-STN-DBS surgery were recorded. Linear regression was used to investigate the relationship between score change and structural volumetric data. RESULTS: A significant relationship was demonstrated between change in List Learning test score and thalamic (left, p = 0.02) and hippocampal (left, p = 0.02 and right p = 0.03) volumes. Duration of symptoms was also associated with List Learning score change (p = 0.02 to 0.03). CONCLUSION: Verbal memory score changes appear to have a relationship to pre-surgical MRI structural volumetric data. The findings of this study provide a basis for further research into the use of pre-surgical MRI to counsel PD patients regarding post-surgical verbal memory changes.

Subcortical structure volumes and correlation to clinical variables in Parkinson's disease.

BACKGROUND AND PURPOSE: MRI studies in Parkinson's Disease have shown volumetric reductions of subcortical structures such as the thalamus, putamen, globus pallidus, and caudate nucleus. However, there are no studies which look at the relationship between subcortical structure volumes and clinical variables, such as age and motor severity scores. METHODS: Brain MRI scans of 47 consecutive PD patients undergoing deep brain stimulation was acquired. Volumetric data of the thalamus, putamen, caudate nucleus, and globus pallidus were extracted and corrected for total intracranial volume. Pearson correlation coefficient (PCC) and general linear modeling (GLM) were then applied to the volumetric and the clinical variable data to explore the relationships between the two. RESULTS: PCC showed a positive correlation between volumes of the left and right thalamus and left and right putamen with increasing duration of disease. GLM demonstrated that duration of symptoms was a significant factor relating to larger left thalamic volume. Male gender was also a significant factor associated with smaller left and right thalamic and right putaminal volumes. CONCLUSIONS: There is a correlation between the volume subcortical structures and clinical variables, particularly the disease duration, in PD. This may not only help understanding the disease process but also patient selection for invasive and noninvasive therapies.

Cognitive predictors of cognitive change following bilateral subthalamic nucleus deep brain stimulation in Parkinson's disease.

The beneficial effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN) for the motor symptoms in advanced Parkinson's disease (PD) are well established. Early in PD, mild cognitive impairment is present in a proportion of patients. Hence, it can also be present in PD patients considered for DBS. The potential impact of even a modest decline post-surgically is a concern because it could result in impaired cognitive function. Therefore, attempts to determine which pre-operative cognitive measures predict post-operative cognitive change warrant further attention. We report our findings in a cohort of 30 routinely operated non-demented patients who underwent detailed neuropsychological assessments on average 7.1 months before and 9.4 months after STN DBS. We report the individual and group differences pre- and post-DBS. Stepwise regression analysis was used to analyse the best cognitive predictors of post-operative cognitive changes. We describe our data in relation to published normative data. Post-STN DBS, the immediate story recall component of verbal memory was the most affected cognitive function showing a significant decline in its group mean with a large effect size. The best predictors for this change were pre-surgical list learning and Full Scale Intelligence Quotient. These results suggest that non-demented patients, with even mild impairments in both general intellectual functions and list learning, may be at greater risk of decline in other aspects of verbal memory after STN DBS. Pre-existing mild executive dysfunction was not influenced post-operatively. These findings may help selection and consent for STN DBS.