Hypothalamic deep brain stimulation [Neurosurgery Wiki]

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====== Hypothalamic deep brain stimulation ======

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Due to its involvement in a wide variety of cardiovascular, metabolic, and behavioral functions, the [[hypothalamus]] constitutes a potential target for [[neuromodulation]] in a number of treatment-refractory conditions. The precise neural substrates and circuitry subserving these responses, however, are poorly characterized to date. 

Neudorfer et al. sought to [[retrospective]]ly explore the acute sequalae of [[hypothalamic region]] deep brain stimulation and characterize their neuroanatomical correlates. To this end they studied at multiple international centers 58 patients (mean age: 68.5 ± 7.9 years, 26 females) suffering from mild [[Alzheimer's disease]] who underwent [[stimulation]] of the [[fornix]] region between 2007 and 2019. They catalogued the diverse spectrum of acutely induced clinical responses during Electrostimulation and interrogated their neural substrates using volume of tissue activated modelling, voxel-wise mapping, and supervised machine learning techniques. In total 627 acute clinical responses to stimulation - including tachycardia, hypertension, flushing, sweating, warmth, coldness, nausea, phosphenes, and fear - were recorded and catalogued across patients using standard descriptive methods. The most common manifestations during hypothalamic region stimulation were tachycardia (30.9%) and warmth (24.6%) followed by flushing (9.1%) and hypertension (6.9%). Voxel-wise mapping identified distinct, locally separable clusters for all sequelae that could be mapped to specific hypothalamic and extrahypothalamic gray- and white-matter structures. K-nearest neighbor classification further validated the clinico-anatomical correlates emphasizing the functional importance of identified neural substrates with area under the receiving operating characteristic curves (AUROC) between 0.67 - 0.91. Overall, they were able to localize acute effects of hypothalamic region stimulation to distinct [[tract]]s and nuclei within the [[hypothalamus]] and the wider [[diencephalon]] providing clinico-anatomical insights that may help to guide future [[neuromodulation]] work
((Neudorfer C, Elias GJB, Jakobs M, Boutet A, Germann J, Narang K, Loh A, Paff M, Horn A, Kucharczyk W, Deeb W, Salvato B, Almeida L, Foote KD, Rosenberg PB, Tang-Wai DF, Anderson WS, Mari Z, Ponce FA, Wolk DA, Burke AD, Salloway S, Sabbagh MN, Chakravarty MM, Smith GS, Lyketsos CG, Okun MS, Lozano AM. Mapping autonomic, mood, and cognitive effects of hypothalamic region deep brain stimulation. Brain. 2021 Apr 26:awab170. doi: 10.1093/brain/awab170. Epub ahead of print. PMID: 33905474.)).

[[Cluster headache]] (CR) is the most severe human [[headache]] and is chronic in 10%-20% of patients, and 10% can become [[refractory]] to all effective [[drug]]s. In this scenario, surgical procedures are indicated: 

see [[Sphenopalatine ganglion stimulation for cluster headache]]

see [[Occipital nerve stimulation for cluster headache]].

Deep brain stimulation (DBS) of the posterior hypothalamus was found to be effective in the treatment of drug-resistant chronic [[cluster headache]]
((Bartsch T, Pinsker MO, Rasche D, Kinfe T, Hertel F, Diener HC, Tronnier V,
Mehdorn HM, Volkmann J, Deuschl G, Krauss JK. Hypothalamic deep brain stimulation
for cluster headache: experience from a new multicase series. Cephalalgia. 2008
Mar;28(3):285-95. doi: 10.1111/j.1468-2982.2007.01531.x. PubMed PMID: 18254897.
)).

===== Case series =====

Bartsch et al. reported the results of a multicentre case series of six patients with chronic [[cluster headache]] in whom a [[DBS]] in the posterior [[hypothalamus]] was performed. Electrodes were implanted stereotactically in the ipsilateral posterior hypothalamus according to published coordinates 2 mm lateral, 3 mm posterior and 5 mm inferior referenced to the mid-AC-PC line. Microelectrode recordings at the target revealed single unit activity with a mean discharge rate of 17 Hz (range 13-35 Hz, n = 4). Out of six patients, four showed a profound decrease of their attack frequency and pain intensity on the visual analogue scale during the first 6 months. Of these, one patient was attack free for 6 months under [[neurostimulation]] before returning to the baseline which led to abortion of the DBS. Two patients had experienced only a marginal, non-significant decrease within the first weeks under neurostimulation before returning to their former attack frequency. After a mean follow-up of 17 months, three patients are almost completely attack free, whereas three patients can be considered as treatment failures. The stimulation was well tolerated and stimulation-related side-effects were not observed on long term. DBS of the posterior inferior hypothalamus is an effective therapeutic option in a subset of patients. Future controlled multicentre trials will need to confirm this open-label experience and should help to better define predictive factors for non-responders
((Bartsch T, Pinsker MO, Rasche D, Kinfe T, Hertel F, Diener HC, Tronnier V,
Mehdorn HM, Volkmann J, Deuschl G, Krauss JK. Hypothalamic deep brain stimulation
for cluster headache: experience from a new multicase series. Cephalalgia. 2008
Mar;28(3):285-95. doi: 10.1111/j.1468-2982.2007.01531.x. PubMed PMID: 18254897.
)).
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[[Hypothalamic deep brain stimulation]]: may respond to hypothalamic stimulation, but larger trials with longer follow-up are needed
((Awan NR, Lozano A, Hamani C. Deep brain stimulation: current and future perspectives. Neurosurg Focus. 2009; 27. DOI: 10.3171/2009.4.FOCUS0982)).