Access Card for Online Flash Cards Deep Brain Stimulation Management

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Deep brain stimulation of the nucleus basalis of Meynert

Deep brain stimulation of the nucleus basalis of Meynert

Deep brain stimulation of the nucleus basalis of Meynert (NBM DBS) has been proposed as a treatment option for Parkinson disease dementia.

Low-frequency NBM DBS was safely conducted in patients with Parkinson disease dementia; however, no improvements were observed in the primary cognitive outcomes. Further studies may be warranted to explore its potential to improve troublesome neuropsychiatric symptoms 1).


Nombela et al., from Hospital Clínico San CarlosToronto Western Hospital, reported a Parkinson’s disease (PD) patient diagnosed with mild cognitive impairment who underwent DBS surgery targeting the Globus pallidus internus (GPi; to treat motor symptoms) and the nucleus basalis of Meynert (NBM; to treat cognitive symptoms) using a single electrode per hemisphere.

Compared to baseline, 2-month follow-up after GPi stimulation was associated with motor improvements, whereas partial improvements in cognitive functions were observed 3 months after the addition of NBM stimulation to GPi stimulation.

This case explores an available alternative for complete DBS treatment in PD, stimulating 2 targets at different frequencies with a single electrode lead 2).


A global experience is emerging for the use of DBS for these conditions, targeting key nodes in the memory circuit, including the fornix and nucleus basalis of Meynert. Such work holds promise as a novel therapeutic approach for one of medicine’s most urgent priorities 3).

A unique feature in the course of both Alzheimer disease (AD) and Parkinson’s dementia (PDD) is basal forebrain degeneration including the latter’s cholinergic projections to the cortex. Neurostimulation of ascending basal forebrain projections of the Nucleus basalis of Meynert (NBM) may, therefore, represent a new strategy for enhancing the residual nucleus basalis output. The relevance of the cholinergic forebrain for brain plasticity has, for instance, been illustrated by the reshaping of auditory receptive fields during and after stimulation of the NBM in the adult brain 4).

Deep brain stimulation of the nucleus basalis of Meynert is thought to positively affect cognition and might counteract the deterioration of nutritional status and progressive weight loss observed in Alzheimer disease (AD).

A study aims to assess the nutritional status of patients with AD before receiving DBS of the nucleus basalis of Meynert and after 1 year, and to analyze potential associations between changes in cognition and nutritional status.

Nutritional status was assessed using a modified Mini Nutritional Assessment, bioelectrical impedance analysis, a completed 3-day food diary, and analysis of serum levels of vitamin B12 and folate.

With a normal body mass index (BMI) at baseline (mean 23.75 kg/m²) and after 1 year (mean 24.59 kg/m²), all but one patient gained body weight during the period of the pilot study (mean 2.38 kg, 3.81% of body weight). This was reflected in a mainly stable or improved body composition, assessed by bioelectrical impedance analysis, in five of the six patients. Mean energy intake increased from 1534 kcal/day (min 1037, max 2370) at baseline to 1736 kcal/day (min 1010, max 2663) after 1 year, leading to the improved fulfillment of energy needs in four patients. The only nutritional factors that were associated with changes in cognition were vitamin B12 level at baseline (Spearman’s rho = 0.943, p = 0.005) and changes in vitamin B12 level (Spearman’s rho = -0.829, p = 0.042).

Patients with AD that received DBS of the nucleus basalis of Meynert demonstrated a mainly stable nutritional status within a 1-year period. Whether DBS is causative regarding these observations must be investigated in additional studies 5).

Case series

Case reports

References

1)

Gratwicke J, Zrinzo L, Kahan J, Peters A, Beigi M, Akram H, Hyam J, Oswal A, Day B, Mancini L, Thornton J, Yousry T, Limousin P, Hariz M, Jahanshahi M, Foltynie T. Bilateral Deep Brain Stimulation of the Nucleus Basalis of Meynert for Parkinson Disease Dementia: A Randomized Clinical Trial. JAMA Neurol. 2018 Feb 1;75(2):169-178. doi: 10.1001/jamaneurol.2017.3762. PubMed PMID: 29255885; PubMed Central PMCID: PMC5838617.
2)

Nombela C, Lozano A, Villanueva C, Barcia JA. Simultaneous Stimulation of the Globus Pallidus Interna and the Nucleus Basalis of Meynert in the Parkinson-Dementia Syndrome. Dement Geriatr Cogn Disord. 2019 Jan 10;47(1-2):19-28. doi: 10.1159/000493094. [Epub ahead of print] PubMed PMID: 30630160.
3)

Sankar T, Lipsman N, Lozano AM. Deep brain stimulation for disorders of memory and cognition. Neurotherapeutics. 2014 Jul;11(3):527-34. doi: 10.1007/s13311-014-0275-0. Review. PubMed PMID: 24777384; PubMed Central PMCID: PMC4121440.
4)

Kilgard MP, Merzenich MM. Cortical map reorganization enabled by nucleus basalis activity. Science (1998) 279(5357):1714–810.1126/science.279.5357.1714
5)

Noreik M, Kuhn J, Hardenacke K, Lenartz D, Bauer A, Bührle CP, Häussermann P, Hellmich M, Klosterkötter J, Wiltfang J, Maarouf M, Freund HJ, Visser-Vandewalle V, Sturm V, Schulz RJ. Changes in Nutritional Status after Deep Brain Stimulation of the Nucleus Basalis of Meynert in Alzheimer’s Disease – Results of a Phase I Study. J Nutr Health Aging. 2015;19(8):812-8. doi: 10.1007/s12603-015-0496-x. PubMed PMID: 26412285.

Dorsal root ganglion stimulation

Neuromodulation of distal targets such as dorsal root ganglion may permit greater anatomic specificity of the therapy, whereas subthreshold stimulation with high-frequency or burst energy delivery may eliminate noxious and off-target paresthesiae. Such new technologies should be subject to rigorous evaluation as their mechanisms of action and long-term outcomes remain hitherto undefined 1).

Indications

Case series

Piedade et al., from University Hospital of Düsseldorf, reported a consecutive series of 20 patients treated with DRG stimulation in the upper thoracic and cervical region. All patients suffered from chronic neuropathic pain unresponsive to best medical treatment. Main pain etiologies were traumaspine surgerypostherpetic neuralgia, and peripheral nerve surgery. All patients were trialed with externalized electrodes prior to permanent pulse generator implantation. Routine clinical follow-up was performed during reprogramming sessions.

Out of all 20 patients trialed, 18 were successfully trialed and implanted with a permanent stimulation system. The average pain relief after three months compared to the baseline was of 60.9% (mean VAS 8.5 to VAS 3.2). 77.8% of the patients reported a pain relief of at least 50% after three months. One patient developed a transient paresis of the arm caused by the procedure. She completely recovered within three months.

Cervical and upper thoracic DRG stimulation resulted in good overall response rates to trialing and similar pain relief when compared to DRG stimulation for groin and lower limb pain. A modified surgical approach has to be used when compared with lumbar DRG electrode placement. Surgery itself in this region is more complication prone and challenging 2).


Morgalla et al., prospectively enrolled 12 adult patients with unilateral localized neuropathic pain in the lower limbs or inguinal region and followed them up for six months Laser evoked potentials (LEP) were assessed at baseline, after one month of DRGS, and after six months of DRGS. Clinical assessment included the Numerical Rating Scale (NRS), Brief Pain Inventory (BPI), SF-36, and Beck Depression Inventory (BDI). For each patient, LEP amplitudes and latencies of the N2 and P2 components on the deafferented side were measured and compared to those of the healthy side and correlated with pain intensity, as measured with the NRS.

At the one- and six-month follow-ups, N2-P2 amplitudes were significantly greater and NRS scores were significantly lower compared with baseline (all p’s < 0.01). There was a negative correlation between LEP amplitudes and NRS scores (rs = -0.31, p < 0.10).

DRGS is able to restore LEPs to normal values in patients with localized neuropathic pain, and LEP alterations are correlated with clinical response in terms of pain intensity 3).

Case reports

van Velsen et al. used a single-incision approach to tunnel and implant the leads and pulse generator for DRG stimulation treatment in a patient suffering from intractable foot pain. At long-term follow-up, the patient experienced a decrease in pain intensity and improvement in function, without any complications. A single-incision implantation technique for DRG stimulator implantation may simplify implantation and decrease the risk of complications 4).

References

1)

Shamji MF, De Vos C, Sharan A. The Advancing Role of Neuromodulation for the Management of Chronic Treatment-Refractory Pain. Neurosurgery. 2017 Mar 1;80(3S):S108-S113. doi: 10.1093/neuros/nyw047. PubMed PMID: 28350939.
2)

Piedade GS, Vesper J, Chatzikalfas A, Slotty PJ. Cervical and High-Thoracic Dorsal Root Ganglion Stimulation in Chronic Neuropathic Pain. Neuromodulation. 2019 Jan 8. doi: 10.1111/ner.12916. [Epub ahead of print] PubMed PMID: 30620789.
3)

Morgalla MH, de Barros Filho MF, Chander BS, Soekadar SR, Tatagiba M, Lepski G. Neurophysiological Effects of Dorsal Root Ganglion Stimulation (DRGS) in Pain Processing at the Cortical Level. Neuromodulation. 2018 Dec 18. doi: 10.1111/ner.12900. [Epub ahead of print] PubMed PMID: 30561852.
4)

van Velsen V, van Helmond N, Levine ME, Chapman KB. Single-Incision Approach to Implantation of the Pulse Generator and Leads for Dorsal Root Ganglion Stimulation: A Case Report. A A Case Rep. 2017 Aug 14. doi: 10.1213/XAA.0000000000000625. [Epub ahead of print] PubMed PMID: 28816708.
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