Ataxia-telangiectasia (A-T) is an autosomal-recessive disorder characterized by cerebellar ataxia, oculocutaneous telangiectasia, immunodeficiency, radiosensitivity, increased prevalence of malignancies, and increased level of alpha-fetoprotein (AFP). 1 The responsible gene A-T mutated (ATM), localized to chromosome 11q22-2, is a serine/threonine protein kinase that is involved in the cellular response to DNA damage.Whereas the classic form, genetically marked by truncating mutations of the ATM, is a severe, fast progressive disease with no residual ATM kinase activity, patients with variant A-T show a milder form of the disease, often presenting with a plethora of different extrapyramidal manifestations-choreoathetosis, resting tremor, and myoclonus-dystonia (M-D) and still have some residual ATM-kinase activity; they are usually carriers of at least one missense or leaky splice site mutation. 1,2We present a case of a variant A-T with mainly M-D presenting features and a favorable outcome after bilateral DBS of the globus pallidus pars interna (GPi-DBS).
Variation in the genetic risk(s) of developing Parkinson's disease (PD) undoubtedly contributes to the subsequent phenotypic heterogeneity. Although patients with PD who undergo deep brain stimulation (DBS) are a skewed population, they represent a valuable resource for exploring the relationships between heterogeneous phenotypes and PD genetics. In this series, 94 patients who underwent DBS were screened for mutations in the most common genes associated with PD. The consequent genetic subgroups of patients were compared with respect to phenotype, levodopa (l-dopa), and DBS responsiveness. An unprecedented number (29%) of patients tested positive for at least 1 of the currently known PD genes. Patients with Parkin mutations presented at the youngest age but had many years of disease before needing DBS, whereas glucocerebrosidase (GBA) mutation carriers reached the threshold of needing DBS earlier, and developed earlier cognitive impairment after DBS. DBS cohorts include large numbers of gene positive PD patients and can be clinically instructive in the exploration of genotype-phenotype relationships.
Subthalamic nucleus deep brain stimulation (STN-DBS) is an established treatment for selected Parkinson's disease (PD) patients, but therapy is often limited by side effects. Previous studies indicate an inverse relationship of the therapeutic window (TW) to pulse width (PW) settings down to 60μs, but there is limited data available on the effect of shorter PWs.To define the TW of STN-DBS in PD at PW of 30μs (PW30) relative to standard PW settings at 60μs (PW60), and to compare speed of gait and speech intelligibility on the two PW conditions.Monopolar review data of 15 consecutive PD patients who had screening of contacts performed at PW60 and PW30 was used to calculate the TW at each contact. We compared the TWs of the most efficacious contact per STN, and a secondary analysis was performed comparing all contacts. Speed of gait with a timed 10 metre walk test, speech intelligibility, and perceptual characteristics of speech were also compared at the efficacy thresholds for PW60 and PW30.The TW was significantly greater at PW30 [3.8±1.6mA] than at PW60 [1.7±1.1mA]. In the secondary analysis, 110 TWs could be calculated and these remained significantly higher at PW30. The timed 10 metre walk at PW30 was faster than at PW60, and perceptual rating scores of speech were significantly improved at PW30.STN-DBS in PD patients using a PW of 30μs significantly increases the TW compared to standard PW settings, and this effect is consistent across all contacts of an electrode. Speed of gait and perceptual speech scores are also improved at 30μs settings.
Subthalamic nucleus (STN) deep brain stimulation (DBS) represents a well-established treatment for patients with advanced Parkinson9s disease (PD) insufficiently controlled with medical therapies. This study presents the long-term outcomes of patients with PD treated with STN-DBS using an MRI-guided/MRI-verified approach without microelectrode recording.
Methods
A cohort of 41 patients who underwent STN-DBS were followed for a minimum period of 5 years, with a subgroup of 12 patients being followed for 8–11 years. Motor status was evaluated using part III of the Unified Parkinson9s Disease Rating Scale (UPDRS-III), in on- and off-medication/on-stimulation conditions. Preoperative and postoperative assessments further included activities of daily living (UPDRS-II), motor complications (UPDRS-IV), neuropsychological and speech assessments, as well as evaluation of quality of life. Active contacts localisation was calculated and compared with clinical outcomes.
Results
STN-DBS significantly improved the off-medication UPDRS-III scores, compared with baseline. However, UPDRS scores increased over time after DBS. Dyskinesias, motor fluctuations and demands in dopaminergic medication remained significantly reduced in the long term. Conversely, UPDRS-III on-medication scores deteriorated at 5 and 8 years, mostly driven by axial and bradykinesia subscores. Quality of life, as well as depression and anxiety scores, did not significantly change at long-term follow-up compared with baseline. In our series, severe cognitive decline was observed in 17.1% and 16.7% of the patients at 5 and 8 years respectively.
Conclusions
Our data confirm that STN-DBS, using an MRI-guided/MRI-verified technique, remains an effective treatment for motor 'off' symptoms of PD in the long term with low morbidity.
OBJECTIVE Infection of deep brain stimulation (DBS) hardware has a significant impact on patient morbidity. Previous experience suggests that infection rates appear to be higher after implantable pulse generator (IPG) replacement surgery than after the de novo DBS procedure. In this study the authors examine the effect of a change in practice during DBS IPG replacements at their institution. METHODS Starting in January 2012, patient screening for methicillin-resistant Staphylococcus aureus (MRSA) and, and where necessary, eradication was performed prior to elective DBS IPG change. Moreover, topical vancomycin was placed in the IPG pocket during surgery. The authors then prospectively examined the infection rate in patients undergoing DBS IPG replacement at their center over a 3-year period with at least 9 months of follow-up. RESULTS The total incidence of infection in this prospective consecutive series of 101 IPG replacement procedures was 0%, with a mean follow-up duration of 24 ± 11 months. This was significantly lower than the authors' previously published historical control group, prior to implementing the change in practice, where the infection rate for IPG replacement was 8.5% (8/94 procedures; p = 0.003). CONCLUSIONS This study suggests that a change in clinical practice can significantly lower infection rates in patients undergoing DBS IPG replacement. These simple measures can minimize unnecessary surgery, loss of benefit from chronic stimulation, and costly hardware replacement, further improving the cost efficacy of DBS therapies.
Subthalamic deep brain stimulation (STN-DBS) is an established treatment for late stage Parkinson's disease (PD). Speech intelligibility (SI) and verbal fluency (VF) have been shown to deteriorate following chronic STN-DBS. It has been suggested that speech might respond favourably to low frequency stimulation (LFS).We examined how SI, perceptual speech characteristics, phonemic and semantic VF and processes underlying it (clustering and switching) respond to LFS of 60 and 80 Hz in comparison to high frequency stimulation (HFS) (110, 130 and 200 Hz).In this double-blind study, 15 STN-DBS PD patients (mean age 65, SD = 5.8, 14 right handed, three females), were assessed at five stimulation frequencies: 60 Hz, 80 Hz, 110 Hz, 130 Hz and 200 Hz. In addition to the clinical neurological assessment of speech, VF and SI were assessed.SI and in particular articulation, respiration, phonation and prosody improved with LFS (all p < 0.05). Phonemic VF switching improved with LFS (p = 0.005) but this did not translate to an improved phonemic VF score. A trend for improved semantic VF was found. A negative correlation was found between perceptual characteristics of speech and duration of chronic stimulation (all p < 0.05).These findings highlight the need for meticulous programming of frequency to maximise SI in chronic STN-DBS. The findings further implicate stimulation frequency in changes to specific processes underlying VF, namely phonemic switching and demonstrate the potential to address such deficits through advanced adjustment of stimulation parameters.
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