Functional Neurosurgery

Parkinson’s disease

Parkinson’s disease

James Parkinson was the first to describe Parkinson’s disease (PD) in 1817; he described it as a combination of tremor, rigidity, postural abnormalities, and bradykinesia.

Definition

Parkinson’s disease is a progressive neurological disorder characterized by the preferential loss of dopaminergic neurons in the substantia nigra, which project to the striatum.

Parkinson’s disease (PD) is a neurodegenerative disease involving the basal ganglia, resulting in motor and extra-motor deficits. These extra-motor deficits may be reflective of a self-regulatory deficit impacting patients’ ability to regulate cognitive processes, thoughts, behaviors, and emotions.

With advances in knowledge disease, boundaries may change. Occasionally, these changes are of such a magnitude that they require redefinition of the disease. In recognition of the profound changes in our understanding of Parkinson’s disease (PD), the International Parkinson and Movement Disorders Society (MDS) commissioned a task force to consider a redefinition of PD.

Several critical issues were identified that challenge current PD definitions. First, new findings challenge the central role of the classical pathologic criteria as the arbiter of diagnosis, notably genetic cases without synuclein deposition, the high prevalence of incidental Lewy body (LB) deposition, and the nonmotor prodrome of PD. It remains unclear, however, whether these challenges merit a change in the pathologic gold standard, especially considering the limitations of alternate gold standards. Second, the increasing recognition of dementia in PD challenges the distinction between diffuse LB disease and PD. Consideration might be given to removing dementia as an exclusion criterion for PD diagnosis. Third, there is increasing recognition of disease heterogeneity, suggesting that PD subtypes should be formally identified; however, current subtype classifications may not be sufficiently robust to warrant formal delineation. Fourth, the recognition of a nonmotor prodrome of PD requires that new diagnostic criteria for early-stage and prodromal PD should be created; here, essential features of these criteria are proposed. Finally, there is a need to create new MDS diagnostic criteria that take these changes in disease definition into consideration 1).

see Parkinson’s Disease Dementia

Classification

Idiopathic Parkinson’s disease

Current subtype classifications may not be sufficiently robust to warrant formal delineation.

see also Tremor predominant Parkinson’s disease.

Sporadic Parkinson’s disease and some genetic forms such as GBA1-associated parkinsonism, LRRK2-associated Parkinson’s disease

Natural History

The natural history of PD may follow a more benign motor-predominant course in some patients, while in others the disabling non-motor features predominate. The underlying basis of the clinical heterogeneity is poorly understood, but it is becoming clear that this is, at least in part, due to genetic factors 2) 3) 4). One of these genetic risk factors is mutation in the GBA1 gene, which has emerged numerically as the most important genetic abnormality associated with PD 5) 6), being found in about 5% of patients with the so-called sporadic PD

Scales

UPDRS

Epidemiology

Parkinson’s Disease Epidemiology.

Etiology

see Parkinson’s disease etiology.

Pathogenesis

Parkinson’s disease Pathogenesis.

Pathophysiology

see Parkinson’s disease pathophysiology.

Pathology

The main neuropathological finding is Alpha-synuclein-containing Lewy bodies and loss of dopaminergic neurons in the substantia nigra, manifesting as reduced facilitation of voluntary movements. With progression of PD, Lewy body pathology spreads to neocortical and cortical regions. Several environmental factors are associated with increased risk of PD. Autopsy studies show that the clinical diagnosis of PD is not confirmed at autopsy in a significant proportion of patients. Revised diagnostic criteria are expected to improve the clinician´s accuracy in diagnosing PD. Increasing knowledge on genetic and environmental risk factors of PD will probably elucidate the cause of this disease within the near future 7)

Clinical Features

see Parkinson’s disease clinical features.

Diagnosis

Parkinson’s disease diagnosis.

Treatment

see Parkinson’s disease treatment.

Outcome

Parkinson’s disease outcome

Parkinson’s disease complications.

Research

Open science and collaboration are necessary to facilitate the advancement of Parkinson’s disease (PD) research. Hackathons are collaborative events that bring together people with different skill sets and backgrounds to generate resources and creative solutions to problems. These events can be used as training and networking opportunities, thus we coordinated a virtual 3-day hackathon event, during which 49 early-career scientists from 12 countries built tools and pipelines with a focus on PD. Resources were created with the goal of helping scientists accelerate their own research by having access to the necessary code and tools. Each team was allocated one of nine different projects, each with a different goal. These included developing post-genome-wide association studies (GWAS) analysis pipelines, downstream analysis of genetic variation pipelines, and various visualization tools. Hackathons are a valuable approach to inspire creative thinking, supplement training in data science, and foster collaborative scientific relationships, which are foundational practices for early-career researchers. The resources generated can be used to accelerate research on the genetics of PD 8).

Meta-analysis

A meta-analysis investigated the effectiveness of short pulse width DBS (spDBS) versus conventional DBS (cDBS) in patients with Parkinson’s disease.

Four databases (PubMed, Cochrane, Web of Science, and Embase) were independently searched until October 2021 by two reviewers. They utilized the following scales and items: therapeutic windows (TW), efficacy threshold, side effect threshold, Movement Disorder Society-Sponsored Revision Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part III off-medication score, Speech Intelligence Test (SIT), and Freezing of Gait Questionnaire (FOG-Q).

The analysis included seven studies with a total of 87 patients. The results indicated that spDBS significantly widened the therapeutic windows (0.99, 95% CI = 0.61 to 1.38) while increasing the threshold amplitudes of side effects (2.25, 95% CI = 1.69 to 2.81) and threshold amplitudes of effects (1.60, 95% CI = 0.84 to 2.36). There was no statistically significant difference in UPDRS part III, SIT, and FOG-Q scores between spDBS and cDBS groups, suggesting that treatment with both cDBS and spDBS may result in similar effects of improved dysarthria and gait disorders.

Compared with cDBS, spDBS is effective in expanding therapeutic windows (TW). Both types of deep brain stimulation resulted in improved gait disorders and speech intelligibility 9)

Case series

see Parkinson’s disease case series.

Case reports

Parkinson´s disease case reports.

1)

Berg D, Postuma RB, Bloem B, Chan P, Dubois B, Gasser T, Goetz CG, Halliday GM, Hardy J, Lang AE, Litvan I, Marek K, Obeso J, Oertel W, Olanow CW, Poewe W, Stern M, Deuschl G. Time to redefine PD? Introductory statement of the MDS Task Force on the definition of Parkinson’s disease. Mov Disord. 2014 Apr;29(4):454-62. doi: 10.1002/mds.25844. Epub 2014 Mar 11. PubMed PMID: 24619848.
2)

Kalia LV, Lang AE. Parkinson’s disease. Lancet. 2015;386(9996):896–912.
3)

Nalls MA, Pankratz N, Lill CM, Do CB, Hernandez DG, Saad M, et al. Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson’s disease. Nat Genet. 2014;46(9):989–93.
4)

Williams-Gray CH, Goris A, Saiki M, Foltynie T, Compston DA, Sawcer SJ, et al. Apolipoprotein E genotype as a risk factor for susceptibility to and dementia in Parkinson’s disease. J Neurol. 2009;256(3):493–8.
5)

Gan-Or Z, Giladi N, Rozovski U, Shifrin C, Rosner S, Gurevich T, et al. Genotype-phenotype correlations between GBA mutations and Parkinson’s disease risk and onset. Neurology. 2008;70(24):2277–83.
6)

Migdalska-Richards A, Schapira AH. The relationship between glucocerebrosidase mutations and Parkinson’s disease. J Neurochem. 2016 Oct;1(139 Suppl):77–90.
7)

Tysnes OB, Storstein A. Epidemiology of Parkinson’s disease. J Neural Transm (Vienna). 2017 Aug;124(8):901-905. doi: 10.1007/s00702-017-1686-y. Epub 2017 Feb 1. PMID: 28150045.
8)

Leonard HL, Murtadha R, Martinez-Carrasco A, Jama A, Müller-Nedebock AC, Gil-Martinez AL, Illarionova A, Moore A, Bustos BI, Jadhav B, Huxford B, Storm C, Towns C, Vitale D, Chetty D, Yu E, Grenn FP, Salazar G, Rateau G, Iwaki H, Elsayed I, Foote IF, Jansen van Rensburg Z, Kim JJ, Yuan J, Lake J, Brolin K, Senkevich K, Wu L, Tan MMX, Periñán MT, Makarious MB, Ta M, Pillay NS, Betancor OL, Reyes-Pérez PR, Alvarez Jerez P, Saini P, Al-Ouran R, Sivakumar R, Real R, Reynolds RH, Hu R, Abrahams S, Rao SC, Antar T, Leal TP, Iankova V, Scotton WJ, Song Y, Singleton A, Nalls MA, Dey S, Bandres-Ciga S, Blauwendraat C, Noyce AJ; International Parkinson Disease Genomics Consortium (IPDGC) and The Global Parkinson’s Genetics Program (GP2). The IPDGC/GP2 Hackathon – an open science event for training in data science, genomics, and collaboration using Parkinson’s disease data. NPJ Parkinsons Dis. 2023 Mar 4;9(1):33. doi: 10.1038/s41531-023-00472-6. PMID: 36871034.
9)

Zou X, Shi Y, Wu X, Ye Q, Lin F, Cai G. Efficacy of short pulse and conventional deep brain stimulation in Parkinson’s disease: a systematic review and meta-analysis. Neurol Sci. 2022 Nov 16. doi: 10.1007/s10072-022-06484-z. Epub ahead of print. PMID: 36383263.

Deep brain stimulation of the nucleus accumbens for alcohol use disorder

Deep brain stimulation of the nucleus accumbens for alcohol use disorder

In recent years, DBS of the nucleus accumbens has been explored as a potential treatment for alcohol use disorder (AUD), also known as alcoholism. The idea is that electrical stimulation of this region may help to regulate the activity of the brain circuits involved in addiction, and thereby reduce the compulsions and cravings associated with alcohol dependence.

DBS of NA in animals reduced addictive behavior to alcohol, cocaine, and other narcotics significantly. The accidental observation that DBS of NA for psychiatric illnesses induced relief from addiction to alcohol and smoking has encouraged further research of late 1).

However, at this time, DBS of the nucleus accumbens for alcohol use disorder is still considered an experimental treatment, and more research is needed to determine its safety and efficacy. Currently, there are only a limited number of studies examining the use of DBS in this context, and the results have been mixed, with some studies showing promising results, while others have not.

It’s important to note that DBS is a highly invasive procedure, and it should only be considered as a last resort after other treatments have failed. A stronger therapeutic rationale based on solid physio-pathological evidence and accurate estimates of efficacy, are still required to achieve further therapeutic success and expand clinical use 2).

Case series

Bach et al. report a double-blind randomized controlled trial comparing active DBS (“DBS-EARLY ON”) against sham stimulation (“DBS-LATE ON”) over 6 months in n = 12 alcohol use disorders (AUD) patients. This 6-month blinded phase was followed by a 12-month unblinded period in which all patients received active DBS. Continuous abstinence (primary outcome), alcohol use, alcohol craving, depression, anxiety, anhedonia and quality of life served as outcome parameters. The primary intention-to-treat analysis, comparing continuous abstinence between treatment groups, did not yield statistically significant results, most likely due to the restricted number of participants. In light of the resulting limited statistical power, there is the question of whether DBS effects on secondary outcomes can nonetheless be interpreted as indicative of a therapeutic effect. Analyses of secondary outcomes provide evidence for this, demonstrating a significantly higher proportion of abstinent days, lower alcohol craving, and anhedonia in the DBS-EARLY ON group 6 months after randomization. Exploratory responder analyses indicated that patients with high baseline alcohol cravings, depressiveness, and anhedonia responded to DBS. The results of this first randomized controlled trial are suggestive of the beneficial effects of DBS in treatment-resistant AUD and encourage replication in larger samples 3).

Six patients with severe, refractory AUD underwent NAc-DBS. Safety metrics and clinical outcomes were recorded. Positron emission tomography (FDG-PET) was used to measure glucose metabolism in the NAc at baseline and 6 months. Functional magnetic resonance imaging (fMRI) was used to characterize postoperative changes in NAc functional connectivity to the rest of the brain, as well as NAc and dorsal striatal reactivity to alcoholic visual cues. This study was registered with ClinicalTrials.gov, NCT03660124. All patients experienced a reduction in cravings. There was a significant reduction in alcohol consumption, alcohol-related compulsivity, and anxiety at 12 months. There was no significant change in depression. FDG-PET analysis demonstrated reduced NAc metabolism by 6 months, which correlated with improvements in compulsive drinking behaviors. Clinical improvement correlated with reduced functional connectivity between the NAc and the visual association cortex. Active DBS was associated with reduced activation of the dorsal striatum during passive viewing of alcohol-containing pictures. NAc-DBS is feasible and safe in patients with severe, otherwise refractory AUD. It is associated with a reduction in cravings and addictive behavior. A potential mechanism underlying this process is a down-regulation of the NAc, a disruption of its functional connectivity to the visual association cortex, and interference of cue-elicited dorsal striatum reactivity. Trial Registration NCT03660124 ( www.clinicaltrials.gov). 4)

1)

Vannemreddy P, Slavin K. Nucleus Accumbens as a Novel Target for Deep Brain Stimulation in the Treatment of Addiction: A Hypothesis on the Neurochemical and Morphological Basis. Neurol India. 2019 Sep-Oct;67(5):1220-1224. doi: 10.4103/0028-3886.271239. PMID: 31744946.
2)

Maatoug R, Bihan K, Duriez P, Podevin P, Silveira-Reis-Brito L, Benyamina A, Valero-Cabré A, Millet B. Non-invasive and invasive brain stimulation in alcohol use disorders: A critical review of selected human evidence and methodological considerations to guide future research. Compr Psychiatry. 2021 Aug;109:152257. doi: 10.1016/j.comppsych.2021.152257. Epub 2021 Jul 3. PMID: 34246194.
3)

Bach P, Luderer M, Müller UJ, Jakobs M, Baldermann JC, Voges J, Kiening K, Lux A, Visser-Vandewalle V; DeBraSTRA study group; Bogerts B, Kuhn J, Mann K. Deep brain stimulation of the nucleus accumbens in treatment-resistant alcohol use disorder: a double-blind randomized controlled multi-center trial. Transl Psychiatry. 2023 Feb 8;13(1):49. doi: 10.1038/s41398-023-02337-1. PMID: 36755017.
4)

Davidson B, Giacobbe P, George TP, Nestor SM, Rabin JS, Goubran M, Nyman AJ, Baskaran A, Meng Y, Pople CB, Graham SJ, Tam F, Hamani C, Lipsman N. Deep brain stimulation of the nucleus accumbens in the treatment of severe alcohol use disorder: a phase I pilot trial. Mol Psychiatry. 2022 Oct;27(10):3992-4000. doi: 10.1038/s41380-022-01677-6. Epub 2022 Jul 21. PMID: 35858989.

Microvascular decompression for hemifacial spasm

Microvascular decompression for hemifacial spasm

see also Hemifacial spasm treatment.

Many ablative procedures are effective for hemifacial spasm (HFS) (including sectioning of divisions of the facial nerve), however, this leaves the patient with some degree of facial paresis. The current procedure of choice for HFS is microvascular decompression (MVD) wherein the offending vessel is physically moved off of the nerve, and a sponge (e.g. Ivalon®, polyvinyl formyl alcohol foam) is interposed as a cushion. Other cushions may not prove to be as satisfactory (muscle may disappear, and Teflon felt may thin 1)).

Most often, the offending vessel approaches the nerve at a right angle, and causes grooving in the nerve. Compression must occur at the root exit zone; decompression of vessels impinging distal to this area is usually ineffective.

Intra-operative brainstem auditory evoked potentials (BAER), 2) or more applicable, direct VIII nerve monitoring 3) may help prevent hearing loss during MVD for 7th or 8th nerve dysfunction. Furthermore, monitoring for the disappearance of the (delayed) synkinetic response may aid in determining when adequate decompression has been achieved (generally reserved for teaching institutions) 4).

The facial nerve should not be manipulated, and one should avoid dissection around the VII and VIII nerves near the IAC 5). Vessels must be preserved, especially the cochlear artery and small perforators. Place gentle medial traction on the cerebellum (<1 cm is recommended 6) ), and incise the arachnoid membrane between the flocculus and the eighth nerve (to avoid tension on nerves that could cause post-op deficit). The IX nerve may be followed medially from the jugular foramen to locate the origin of the VII nerve (the origin of VII is 4 mm cephalad and 2 mm anterior to that of the IX nerve 7)).

Redo MVD remains a feasible treatment option for HFS patients who have failed to benefit from prior MVD, but is associated with higher risks of cranial nerve and vascular injuries 8).

Planning

Three-dimensional reconstructions were found to provide much clearer characterization of this area than traditional preoperative imaging. Therefore, Teton et al., suggest that use of these reconstructions in the preoperative setting has the potential to help identify appropriate surgical candidates, guide preoperative planning, and thus improve outcome in patients with HFS 9).

Position

The classic surgical position for microvascular decompression (MVD) is lateral decubitus position with the head rotated 10 degrees away from the affected side.

Ko et al. measured the angles of the posterior fossa, specifically focusing on the surgical corridors used in MVD surgery for hemifacial spasm (HFS), to identify the proper surgical position.

The following parameters were assessed on preoperative magnetic resonance images (MRI): petrous angle (PA), sigmoid angle (SA), sigmoid diameter (SD), and root exit zone-sigmoid sinus edge angle (REZ-SEA).

The mean PA was 59.7 ± 5.6 degrees, SA was 16.8 ± 8.6 degrees, SD was 13.4 ± 3.5 mm, and the mean REZ-SEA was 59.6 ± 5.8 degrees. The difference between the maximum SA to avoid cerebellar hemisphere injury and the minimum REZ-SEA required to verify the facial nerve REZ is assumed to be the usable range of angles for the operative microscope; the average midpoint of this range was 38.2 ± 6.4 degrees.

Turning the patient’s head 10 degrees away from the affected side was generally appropriate for performing MVD surgery because it provided a mean microscope angle of 48 degrees. However, some patients had corner values for the sigmoid angle, REZ-SEA, and sigmoid sinus diameter. Rotating a patient’s head based on precise calculations from preoperative MRI helps to achieve successful surgery 10).

Skin incision

“5–5-5” incision (5mm medial, extending 5cm up to 5cm down), used for approach to seventh/ eighth nerve complex:

Videos

A video demonstrates the surgical steps of a MVD at left facial REZ in a 41-year-old man who presented with typical hemifacial spasm on the left side due to VIIth nerve REZ compression by PICA. A classical retromastoid and infrafloccular approach was performed to avoid stretching of the VIIIth nerve and access the VIIth nerve ventro-caudally. The next step is insertion-along the brainstem, VII-VIIIth nerves REZ, and flocculus-of a plaque made of Teflon felt (Edward-type) which is semi-rigid, and by principle does not exert direct compression on the facial REZ, thus avoiding compression and/or transmission of pulsations on the VIIth nerve. The patient’s postoperative period was uneventful and clinical outcome good 11)

Routine postoperative admission

Postoperative neurocritical intensive care unit (NICU) admission of patients who underwent craniotomy for close observation is common practice. Hatipoglu Majernik et al. performed a comparative analysis to determine if there is a real need for NICU admission after microvascular decompression (MVD) for cranial nerve disorders or whether it may be abandoned. The study evaluates a consecutive series of 236 MVD surgeries performed for treatment of trigeminal neuralgia (213), hemifacial spasm (17), vagoglossopharyngeal neuralgia (2), paroxysmal vertigo (2), and pulsatile tinnitus (2). All patients were operated by the senior surgeon according to a standard protocol over a period of 12 years. Patients were admitted routinely to NICU during the first phase of the study (phase I), while in the second phase (phase II), only patients with specific indications would go to NICU. While 105 patients (44%) were admitted to NICU postoperatively (phase I), 131 patients (56%) returned to the ward after a short stay in a postanaesthesia care unit (PACU) (phase II). Specific indications for NICU admission in phase I were pneumothorax secondary to central venous catheter insertion (4 patients), AV block during surgery, low blood oxygen levels after extubation, and postoperative dysphagia and dysphonia (1 patient, respectively). There were no significant differences in the distribution of ASA scores or the presence of cardiac and pulmonary comorbidities like congestive heart failure, arterial hypertension, or chronic obstructive pulmonary disease between groups. There were no secondary referrals from PACU to NICU. Our study shows that routine admission of patients after eventless MVD to NICU does not provide additional value. NICU admission can be restricted to patients with specific indications. When MVD surgery is performed in experienced hands according to a standard anaesthesia protocol, clinical observation on a neurosurgical ward is sufficient to monitor the postoperative course. Such a policy results in substantial savings of costs and human resources 12).

Outcome

Microvascular decompression for hemifacial spasm outcome

Complications

see Microvascular decompression for hemifacial spasm complications.

Transposition in microvascular decompression for hemifacial spasm

Transposition in microvascular decompression for hemifacial spasm.

Case series

Al Menabbawy et al. extracted retrospective data of patients who received Indocyanine green videoangiography from a prospectively maintained database for microvascular decompression. They noted relevant data including demographics, offending vessels, operative technique, outcome, and complications.

Out of the 438 patients, 15 patients with a mean age (SD) of 53 ± 10.5 years underwent intraoperative ICG angiography. Male: female was 1:1.14. The mean disease duration prior to surgery was 7.7 ± 5.3 years. The mean follow-up (SD) was 50.7 ± 42.0 months. In 14 patients, the offending vessel was an artery, and in one patient, a vein. Intraoperative readjustment of the Teflon pledget or sling was required in 20% (3/15) of the cases. No patient had any sort of brainstem ischemia. Eighty percent of the patients (12/15) experienced complete resolution of the spasms. 86.7% (13/15) of the patients reported a satisfactory outcome with marked improvement of the spasms. Three patients experienced slight hearing affection after surgery, which improved in two patients later. There was no facial or lower cranial nerve affection.

Intraoperative ICG is a safe tool for evaluating the flow within the brain stem perforators and avoiding brainstem stroke in MVD for hemifacial spasm 13).

References

1)

Rhoton AL. Comment on Payner T D and Tew J M: Recurrence of Hemifacial Spasm After Microvascular Decompression. Neurosurgery. 1996; 38
2)

Friedman WA, Kaplan BJ, Gravenstein D, et al. Int raoperative Brain-Stem Auditory Evoked Potentials During Posterior Fossa Microvascular Decompression. J Neurosurg. 1985; 62:552–557
3)

Moller AR, Jannetta PJ. Monitoring Auditory Functions During Cranial Nerve Microvascular Decompression Operations by Direct Recording from the Eighth Nerve. J Neurosurg. 1983; 59:493–499
4)

Moller AR, Jannetta PJ. Microvascular Decompression in Hemifacial Spasm: Intraoperative Electrophysiological Observations. Neurosurgery. 1985; 16:612–618
5) , 6)

Fukushima T, Carter LP, Spetzler RF, Hamilton MG. In: Microvascular Decompression for Hemifacial Spasm: Results in 2890 Cases. Neurovascular Surgery. New York: McGraw-Hill; 1995:1133–1145
7)

Rhoton AL. Microsurgical Anatomy of the Brainstem Surface Facing an Acoustic Neuroma. Surg Neurol. 1986; 25:326–339
8)

Lee S, Park SK, Lee JA, Joo BE, Park K. Missed Culprits in Failed Microvascular Decompression Surgery for Hemifacial Spasm and Expenses for Redo Surgery. World Neurosurg. 2019 May 31. pii: S1878-8750(19)31508-6. doi: 10.1016/j.wneu.2019.05.231. [Epub ahead of print] PubMed PMID: 31158550.
9)

Teton ZE, Blatt D, Holste K, Raslan AM, Burchiel KJ. Utilization of 3D imaging reconstructions and assessment of symptom-free survival after microvascular decompression of the facial nerve in hemifacial spasm. J Neurosurg. 2019 Jul 12:1-8. doi: 10.3171/2019.4.JNS183207. [Epub ahead of print] PubMed PMID: 31299649.
10)

Ko HC, Lee SH, Shin HS. Proper Head Rotation when Performing Microvascular Decompression for Hemifacial Spasm: An Orthometric Consideration Based on Preoperative MRI. J Neurol Surg A Cent Eur Neurosurg. 2022 Feb 15. doi: 10.1055/s-0041-1725950. Epub ahead of print. PMID: 35170003.
11)

Sindou M, Esqueda-Liquidano M, Brinzeu A. Microvascular Decompression for Hemifacial Spasm. Neurosurgery. 2014 Sep 24. [Epub ahead of print] PubMed PMID: 25255262.
12)

Hatipoglu Majernik G, Wolff Fernandes F, Al-Afif S, Heissler HE, Palmaers T, Atallah O, Scheinichen D, Krauss JK. Routine postoperative admission to the neurocritical intensive care unit after microvascular decompression: necessary or can it be abandoned? Neurosurg Rev. 2022 Dec 9;46(1):12. doi: 10.1007/s10143-022-01910-4. PMID: 36482263.
13)

Al Menabbawy A, Refaee EE, Shoubash L, Matthes M, Schroeder HWS. The value of intraoperative indocyanine green angiography in microvascular decompression for hemifacial spasm to avoid brainstem ischemia. Acta Neurochir (Wien). 2022 Oct 27. doi: 10.1007/s00701-022-05389-2. Epub ahead of print. Erratum in: Acta Neurochir (Wien). 2022 Nov 28;: PMID: 36289111.

Deep Brain Stimulation for Post-Traumatic Stress Disorder

Deep Brain Stimulation for Post-Traumatic Stress Disorder

In 2018 the application of DBS for PTSD was still strictly investigational and animal models suggest that stimulation of the amygdala, ventral striatum, hippocampus, and prefrontal cortex may be effective in fear extinction and anxiety-like behavior 1).

Neuroimaging, preclinical, and preliminary clinical data suggested that the use of DBS for the treatment of PTSD may be practical 2).

PTSD is the only potential clinical indication for DBS that shows extensive animal research prior to human applications. Nevertheless, DBS for PTSD remains highly investigational. Despite several years of government funding of DBS research in view of treating severe PTSD in combat veterans, ethical dilemmas, recruitment difficulties, and issues related to use of DBS in such a complex and heterogenous disorder remain prevalent 3).

Hamani et al. treated four posttraumatic stress disorder (PTSD) patients with DBS delivered to the subgenual cingulum and the uncinate fasciculus. In addition to validated clinical scales, patients underwent neuroimaging studies and psychophysiological assessments of fear conditioning, extinction, and recall. They show that the procedure is safe and potentially effective (55% reduction in Clinical Administered PTSD Scale scores). Posttreatment imaging data revealed metabolic activity changes in PTSD neurocircuits. During psychophysiological assessments, patients with PTSD had higher skin conductance responses when tested for recall compared to healthy controls. After DBS, this objectively measured variable was significantly reduced. Last, they found that a ratio between recall of extinguished and nonextinguished conditioned responses had a strong correlation with clinical outcomes. As this variable was recorded at baseline, it may comprise a potential biomarker of treatment response 4).

Amygdala Deep Brain Stimulation for Post-Traumatic Stress Disorder

Functional neuroimaging studies have suggested that amygdala hyperactivity is responsible for the symptoms of PTSD. Deep brain stimulation (DBS) can functionally reduce the activity of a cerebral target by delivering an electrical signal through an electrode. We tested whether DBS of the amygdala could be used to treat PTSD symptoms. Rats traumatized by inescapable shocks, in the presence of an unfamiliar object, develop the tendency to bury the object when re-exposed to it several days later. This behavior mimics the symptoms of PTSD. 10 Sprague-Dawley rats underwent the placement of an electrode in the right basolateral nucleus of the amygdala (BLn). The rats were then subjected to a session of inescapable shocks while being exposed to a conspicuous object (a ball). Five rats received DBS treatment while the other 5 rats did not. After 7 days of treatment, the rats were re-exposed to the ball and the time spent burying it under the bedding was recorded. Rats treated with BLn DBS spent on average 13 times less time burying the ball than the sham control rats. The treated rats also spent 18 times more time exploring the ball than the sham control rats. In conclusion, the behavior of treated rats in this PTSD model was nearly normalized. We argue that these results have direct implications for patients suffering from treatment-resistant PTSD by offering a new therapeutic strategy 5)

1)

Lavano A, Guzzi G, Della Torre A, Lavano SM, Tiriolo R, Volpentesta G. DBS in Treatment of Post-Traumatic Stress Disorder. Brain Sci. 2018 Jan 20;8(1):18. doi: 10.3390/brainsci8010018. PMID: 29361705; PMCID: PMC5789349.
2)

Reznikov R, Hamani C. Posttraumatic Stress Disorder: Perspectives for the Use of Deep Brain Stimulation. Neuromodulation. 2016 Dec 19. doi: 10.1111/ner.12551. [Epub ahead of print] Review. PubMed PMID: 27992092.
3)

Meeres J, Hariz M. Deep Brain Stimulation for Post-Traumatic Stress Disorder: A Review of the Experimental and Clinical Literature. Stereotact Funct Neurosurg. 2022 Jan 3:1-13. doi: 10.1159/000521130. Epub ahead of print. PMID: 34979516.
4)

Hamani C, Davidson B, Corchs F, Abrahao A, Nestor SM, Rabin JS, Nyman AJ, Phung L, Goubran M, Levitt A, Talakoub O, Giacobbe P, Lipsman N. Deep brain stimulation of the subgenual cingulum and uncinate fasciculus for the treatment of posttraumatic stress disorder. Sci Adv. 2022 Dec 2;8(48):eadc9970. doi: 10.1126/sciadv.adc9970. Epub 2022 Dec 2. PMID: 36459550.
5)

Langevin JP, De Salles AA, Kosoyan HP, Krahl SE. Deep brain stimulation of the amygdala alleviates post-traumatic stress disorder symptoms in a rat model. J Psychiatr Res. 2010 Dec;44(16):1241-5. doi: 10.1016/j.jpsychires.2010.04.022. Epub 2010 May 26. PMID: 20537659.

Temporal lobe epilepsy

Temporal lobe epilepsy

Mesial temporal sclerosis (MTS) is the most common cause of intractable temporal lobe epilepsy.

Clinical features

Temporal lobe epilepsy (TLE) is a chronic neurological condition characterized by recurrent seizures (epilepsy) which originate in the temporal lobe with progressive neurological disabilities, including cognitive deficit, anxiety and depression.

The seizures involve sensory changes, for example smelling an unusual odour that is not there, and disturbance of memory.

Treatment

Based on the promising results of randomized controlled trials, deep brain stimulation (DBS) and responsive neurostimulation (RNS) are increasingly used in the treatment of patients with drug-resistant epilepsy. Drug-resistant temporal lobe epilepsy (TLE) is an indication of either DBS of the anterior nucleus of the thalamus (ANT) or temporal lobe (TL) RNS, but there are no studies that directly compare seizure benefits and adverse effects associated with these therapies in this patient population.

Mesial temporal lobe epilepsy

Mesial temporal lobe epilepsy.

Neocortical temporal lobe epilepsy

Neocortical temporal lobe epilepsy

Unilateral temporal lobe epilepsy

Unilateral temporal lobe epilepsy

Case series

Sixty patients with drug-resistant temporal lobe epilepsy who underwent anterior temporal lobectomy were enrolled. Anterior hippocampal samples were collected after surgery and analyzed by immunofluorescence (n = 7/group). They also evaluated the expression of HMGB1 in TLE patients with hippocampal sclerosis and measured the level of plasma HMGB1 by enzyme-linked immunosorbent assay. The results showed that 28.3% of the patients (17/60) had comorbid depression. HMGB1 was ubiquitously expressed in all subregions of the anterior hippocampus. The ratio of HMGB1-immunoreactive neurons and astrocytes was significantly increased in both TLE patients with hippocampal sclerosis and TLE patients with comorbid depression compared to patients with TLE only. The ratio of cytoplasmic to nuclear HMGB1-positive neurons in the hippocampus was higher in depressed patients with TLE than in non-depressed patients, which suggested that more HMGB1 translocated from the nucleus to the cytoplasm in the depressed group. There was no significant difference in the plasma level of HMGB1 among patients with TLE alone, TLE with hippocampal sclerosis, and TLE with comorbid depression. The results of the study revealed that the translocation of HMGB1 from the nucleus to the cytoplasm in hippocampal neurons may play a previously unrecognized role in the initiation and amplification of epilepsy and comorbid depression. The direct targeting of neural HMGB1 is a promising approach for anti-inflammatory therapy 1)

Yang et al., therefore, examined all patients who underwent ANT-DBS or TL-RNS for drug-resistant TLE.

They performed a retrospective review of patients who were treated with either ANT-DBS or TL-RNS for drug-resistant TLE with at least 12 months of follow-up. Along with the clinical characteristics of each patient’s epilepsy, seizure frequency was recorded throughout each patient’s postoperative clinical course.

26 patients underwent ANT-DBS implantation, and 32 patients underwent TL-RNS for drug-resistant TLE. Epilepsy characteristics of both groups were similar. Patients who underwent ANT-DBS demonstrated a median seizure reduction of 58% at 12-15 months, compared to a median seizure reduction of 70% at 12-15 months in patients treated with TL-RNS (p > 0.05). The responder rate (percentage of patients with a 50% decrease or more in seizure frequency) was 54% for ANT-DBS and 56% for TL-RNS (p > 0.05). Incidence of complications and stimulation-related side effects did not significantly differ between therapies.

They demonstrated in a single-center experience that patients with drug-resistant TLE benefit similarly from either ANT-DBS or TL-RNS. Selection of either ANT-DBS or TL-RNS may therefore depend more heavily on patient and provider preference, as each has unique capabilities and configurations. Future studies will consider subgroup analyses to determine if specific patients have greater seizure frequency reduction from one form of neuromodulation strategy over another 2).

1)

Li XL, Wang S, Tang CY, Ma HW, Cheng ZZ, Zhao M, Sun WJ, Wang XF, Wang MY, Li TF, Qi XL, Zhou J, Luan GM, Guan YG. Translocation of High Mobility Group Box 1 From the Nucleus to the Cytoplasm in Depressed Patients With Epilepsy. ASN Neuro. 2022 Jan-Dec;14:17590914221136662. doi: 10.1177/17590914221136662. PMID: 36383501.
2)

Yang JC, Bullinger KL, Dickey AS, Karakis I, Alwaki A, Cabaniss BT, Winkel D, Rodriguez-Ruiz A, Willie JT, Gross RE. Anterior Nucleus of the Thalamus Deep Brain Stimulation Versus Temporal Lobe Responsive Neurostimulation for Temporal Lobe Epilepsy. Epilepsia. 2022 Jun 15. doi: 10.1111/epi.17331. Epub ahead of print. PMID: 35704344.

Bilateral anterior cingulotomy

Bilateral anterior cingulotomy

Bilateral anterior cingulotomy is a form of psychosurgery, introduced in 1948 as an alternative to lobotomy.

Lesioning of the target area is typically performed using bilateral stereotactic electrode placement and target ablation, which involves transparenchymal access through both hemispheres.

Lauri Laitinen was a pioneer of stereotactic psychosurgery in the 1950s to 1970s, especially by introducing the subgenual cingulotomy.

Indications

Bilateral anterior cingulotomy has been used to treat chronic pain, obsessive-compulsive disorder.

In the early years of the twenty-first century, it was used in Russia to treat addiction.

The objective of this surgical procedure is the severing of the supracallosal fibers of the cingulum bundle, which pass through the anterior cingulate gyrus.

Early localizationists linked anterior cingulate cortex (ACC: Brodmann’s area 24 and adjacent regions) with emotional behavior, paving the way for bilateral cingulotomy psychosurgery in severe, treatment resistant, cases of obsessive-compulsive disorder, chronic pain, depression, and substance abuse.

Limbic system surgery based on initial cingulotomy offers a durable and effective treatment option for appropriately selected patients with severe obsessive compulsive disorder who have not responded to conventional pharmacotherapy or psychotherapy 1).

There are features of anterior cingulate cortex structure and connectivity that predict clinical response to dorsal anterior cingulotomy for refractory obsessive compulsive disorder. These results suggest that the variability seen in individual responses to a highly consistent, stereotyped procedure may be due to neuroanatomical variation in the patients. Furthermore, these variations may allow us to predict which patients are most likely to respond to cingulotomy, thereby refining our ability to individualize this treatment for refractory psychiatric disorders 2)

The presence of neuropathic pain can severely impinge on emotional regulation and activities of daily living including social activities, resulting in diminished life satisfaction. Unfortunately, the majority of patients with neuropathic pain do not experience an amelioration of symptoms from conventional therapies, even when multimodal therapies are used. Chronic refractory neuropathic pain is usually accompanied by severe depression that is prone to incur suicidal events; thus clinical management of chronic neuropathic pain and depression presents a serious challenge for clinicians and patients

Two patients presented with neuropathic pain and severe depression. The patients had different pain symptoms emerging a few months after central or peripheral nervous system impairment. These symptoms were associated with the development of severe depression, social isolation, and a gradual inability to perform daily activities. Both patients were referred for bilateral anterior cingulotomy. After surgery, both patients showed significant progressive improvements in perceived pain, mental health status, and daily functioning.

Bilateral anterior cingulotomy may serve as an alternative treatment for medically refractory neuropathic pain, especially for patients who also experience depression 3).

Stereotactic anterior cingulotomy has been used in the treatment of patients suffering from refractory oncological pain due to its effects on pain perception. However, the optimal targets as well as suitable candidates and outcome measures have not been well defined. We report our initial experience in the ablation of 2 cingulotomy targets on each side and the use of the Brief Pain Inventory (BPI) as a perioperative assessment tool.

A retrospective review of all patients who underwent stereotactic anterior cingulotomy in our Department between November 2015 and February 2017 was performed. All patients had advanced metastatic cancer with a limited prognosis and suffered from intractable oncological pain.

Thirteen patients (10 women and 3 men) underwent 14 cingulotomy procedures. Their mean age was 54 ± 14 years. All patients reported substantial pain relief immediately after the operation. Out of the 6 preoperatively bedridden patients, 3 started ambulating shortly after. At the 1-month follow-up, the mean preoperative Visual Analogue Scale score decreased from 9 ± 0.9 to 4 ± 2.7 (p = 0.003). Mean BPI pain severity and interference scores decreased from levels of 29 ± 4 and 55 ± 12 to 16 ± 12 (p = 0.028) and 37 ± 15 (p = 0.043), respectively. During the 1- and 3-month follow-up visits, 9/11 patients (82%) and 5/7 patients (71%) available for follow-up reported substantial pain relief. No patient reported worsening of pain during the study period. Neuropsychological analyses of 6 patients showed stable cognitive functions with a mild nonsignificant decline in focused attention and executive functions. Adverse events included transient confusion or mild apathy in 5 patients (38%) lasting 1-4 weeks.

The initial experience indicates that double stereotactic cingulotomy is safe and effective in alleviating refractory oncological pain 4).

Case series

Four MRgLITT bilateral cingulotomy procedures were performed in 3 patients. Two patients had a single MRgLITT procedure while the third had repeat ablation after pain recurrence. First time ablation coordinates were (medians): x = 7.9 mm (range, 6.9-8.6); y = 20.5 mm (range, 20-22); z = 6.9 mm (range, 2.9-7.0) above the lateral ventricle roof. Median trajectory length was 85.5 mm (range, 80-90). Median ablation volume was 1.5 cm3 (range, 0.6-1.2). Median ablation time was 257 seconds (range, 136-338) per cingulum and power was 10.0 Watts (range, 10-11). Median preoperative pain severity (PSS) and interference scores (PIS) were 7.7 (range, 7.5-9.3) and 9.9 (range, 9.7-10.0), respectively. Median postoperative PSS and PIS scores were 1.6 (range, 1.0-2.8) and 2.0 (range, 0.3-2.6), respectively.

MRgLITT cingulotomy is well tolerated for treatment of cancer pain and can be easily performed framelessly for appropriate candidates 5).

Seven patients suffering from refractory OCD underwent stereotactic surgery and were followed for 12 months. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was used to assess the efficacy. The test was taken before and 6 and 12 months after surgery.

The mean Y-BOCS scores decreased significantly from 32.9 ± 4.7 at baseline to 20.6 ± 5.3 after 12 months. Five out of the 7 patients showed a decrease of more than 35%. During the 12-month follow-up, the effective rate had increased from 28.6 to 71.4%. There were no significant adverse effects observed after surgery.

The BACI and BACA were effective for the treatment of refractory OCD, and no significant adverse effects on long-term follow-up were found 6).

Bilateral radiofrequency cingulotomy was performed in 10 patients. The technique involved stereotaxis using magnetic resonance guidance and local anesthesia, with the placement of a radiofrequency lesion (75 degrees, 60s). Of the 10 patients, 8 had metastatic lesions with musculoskeletal (6) or neurogenic (2) pain. Pain relief was judged excellent (4 patients), fair (1), poor (2) and excellent for 6 months poor in the last patient. The two benign lesions were neurofibromatosis with neurogenic pain and thalamic pain from an old stroke. Pain relief (with 1 year follow-up) in this group was judged excellent in one and poor in the other (thalamic pain) 7).

Forty-two patients out of 300 who had undergone bilateral stereotactic cingulotomies were studied by means of computerized tomography (CT). The appearance showed bilateral encephalomalacia, measuring on the average 5 X 7 mm2, located in the cingulate gyrus. These induced lesions had attenuation values similar to cerebrospinal fluid and did not enhance with contrast. CT is a useful technique for initial evaluation, management, and follow up of these patients 8).

Case reports

In end-stage cancer, oncologic pain refractory to medical management significantly reduces patient’s quality of life. In recent years, ablative surgery has seen a resurgence in treating diffuse and focal cancer pain in terminal patients. The anterior cingulate gyrus has been a key focus as it plays a role in the cognitive and emotional processing of pain. While radiofrequency ablation of the dorsal anterior cingulate is well-described for treating cancer pain, MRI-guided laser-induced thermal therapy (LITT) is novel. Allam et al. describes a patient treated with an MRI-guided LITT therapy of the anterior cingulate gyrus for intractable debilitating pain secondary to terminal metastatic cancer 9).

Huotarinen et al., found 1 patient alive who underwent subgenual cingulotomy in 1971 for obsessive thoughts, anxiety, and compulsions, diagnosed at that time as “schizophrenia psychoneurotica.” MRI showed bilateral subgenual cingulotomy lesions (254 and 160 mm3, respectively). The coordinates of the center of the lesions in relation to the midcommissural point for the right and left, respectively, were: 7.1 and 7.9 mm lateral; 0.2 mm inferior and 1.4 mm superior, and 33.0 and 33.9 anterior, confirming correct subgenual targeting. The patient reported retrospective satisfactory results.

The lesion in this patient was found to be in the expected location, which gives some verification of the correct placement of Laitinen’s subgenus cingulotomy target 10).

A case of debilitating thoracic wall pain due to malignant mesothelioma relieved by bilateral anterior cingulotomy is described and changes in dyspnoea investigated.

Improvements in pain, dyspnoea and the extent to which either symptom bothered the patient was seen for 2 months after surgery before disease progression led to death 5 months after surgery. Quality of life improvements were also seen for 2 months after surgery and pain relief was sustained from surgery to death. Arterial blood gas and lung function tests were unchanged by surgery, suggesting a reduction in pain and dyspnoea awareness by cingulotomy.

Bilateral anterior cingulotomy effectively relieved both pain and dyspnoea. The role of the anterior cingulate cortex in pain and autonomic control of respiration is discussed alongside the evidence for this palliative procedure for cancer pain 11).

Books

by Ernest. Feigenbaum (Author)

References

1)

Sheth SA, Neal J, Tangherlini F, Mian MK, Gentil A, Cosgrove GR, Eskandar EN, Dougherty DD. Limbic system surgery for treatment-refractory obsessive-compulsive disorder: a prospective long-term follow-up of 64 patients. J Neurosurg. 2013 Mar;118(3):491-7. doi: 10.3171/2012.11.JNS12389. Epub 2012 Dec 14. PubMed PMID: 23240700.
2)

Banks GP, Mikell CB, Youngerman BE, Henriques B, Kelly KM, Chan AK, Herrera D, Dougherty DD, Eskandar EN, Sheth SA. Neuroanatomical Characteristics Associated With Response to Dorsal Anterior Cingulotomy for Obsessive-Compulsive Disorder. JAMA Psychiatry. 2014 Dec 23. doi: 10.1001/jamapsychiatry.2014.2216. [Epub ahead of print] PubMed PMID: 25536384.
3)

Deng Z, Pan Y, Li D, Zhang C, Jin H, Wang T, Zhan S, Sun B. Effect of Bilateral Anterior Cingulotomy on Chronic Neuropathic Pain with Severe Depression. World Neurosurg. 2019 Jan;121:196-200. doi: 10.1016/j.wneu.2018.10.008. Epub 2018 Oct 10. PubMed PMID: 30315971.
4)

Strauss I, Berger A, Ben Moshe S, Arad M, Hochberg U, Gonen T, Tellem R. Double Anterior Stereotactic Cingulotomy for Intractable Oncological Pain. Stereotact Funct Neurosurg. 2018 Jan 10;95(6):400-408. doi: 10.1159/000484613. [Epub ahead of print] PubMed PMID: 29316566.
5)

Patel NV, Agarwal N, Mammis A, Danish SF. Frameless stereotactic magnetic resonance imaging-guided laser interstitial thermal therapy to perform bilateral anterior cingulotomy for intractable pain: feasibility, technical aspects, and initial experience in 3 patients. Neurosurgery. 2015 Mar;11 Suppl 2:17-25; discussion 25. doi: 10.1227/NEU.0000000000000581. PubMed PMID: 25584953.
6)

Zhang QJ, Wang WH, Wei XP. Long-term efficacy of stereotactic bilateral anterior cingulotomy and bilateral anterior capsulotomy as a treatment for refractory obsessive-compulsive disorder. Stereotact Funct Neurosurg. 2013;91(4):258-61. doi: 10.1159/000348275. Epub 2013 May 7. PubMed PMID: 23652367.
7)

Pillay PK, Hassenbusch SJ. Bilateral MRI-guided stereotactic cingulotomy for intractable pain. Stereotact Funct Neurosurg. 1992;59(1-4):33-8. PubMed PMID: 1295044.
8)

Bernad PG, Ballantine HT. Computed tomographic analysis of bilateral cingulotomy for intractable mood disturbance and chronic pain. Comput Radiol. 1987 May-Jun;11(3):117-23. PubMed PMID: 3301189.
9)

Allam AK, Larkin MB, Katlowitz KA, Shofty B, Viswanathan A. Case report: MR-guided laser induced thermal therapy for palliative cingulotomy. Front Pain Res (Lausanne). 2022 Nov 1;3:1028424. doi: 10.3389/fpain.2022.1028424. PMID: 36387414; PMCID: PMC9663803.
10)

Huotarinen A, Kivisaari R, Hariz M. Laitinen’s Subgenual Cingulotomy: Anatomical Location and Case Report. Stereotact Funct Neurosurg. 2018;96(5):342-346. doi: 10.1159/000492058. Epub 2018 Oct 2. PubMed PMID: 30278436.
11)

Pereira EA, Paranathala M, Hyam JA, Green AL, Aziz TZ. Anterior cingulotomy improves malignant mesothelioma pain and dyspnoea. Br J Neurosurg. 2014 Aug;28(4):471-4. doi: 10.3109/02688697.2013.857006. Epub 2013 Nov 7. PubMed PMID: 24199940.

Deep brain stimulation (DBS)

Deep brain stimulation (DBS)

General information

Deep brain stimulation (DBS): Neurosurgical procedure that uses electrical stimulation through surgically implanted electrodes to produce neuromodulation of electrical signals for the purpose of symptom improvement. For many indications, DBS has supplanted ablative procedures in the brain.

Deep brain stimulation (DBS) is a neurosurgical procedure introduced in 1987, involving the implantation of a medical device called a neurostimulator (sometimes referred to as a ‘brain pacemaker’), which sends electrical impulses, through implanted electrodes.

The system consists of a lead that is implanted into a specific deep brain target. The lead is connected to an implantable pulse generator (IPG), which is the power source of the system. The lead and the IPG are connected by an extension wire that is tunneled under the skin between both of them. This system is used to chronically stimulate the deep brain target by delivering a high-frequency current to this target.

Deep brain stimulation of different targets has been shown to drastically improve symptoms of a variety of neurological conditions. However, the occurrence of disabling side effects may limit the ability to deliver adequate amounts of current necessary to reach the maximal benefit. Computed models have suggested that reduction in electrode size and the ability to provide directional lead stimulation could increase the efficacy of such therapies 1).

Deep brain stimulation surgery, create an opportunity to conduct cognitive or behavioral experiments during the acquisition of invasive neurophysiology. Optimal design and implementation of intraoperative behavioral experiments require consideration of stimulus presentation, time and surgical constraints. Tekriwal et al., describe the use of a modular, inexpensive system that implements a decision-making paradigm, designed to overcome challenges associated with the operative environment.

They created an auditory, two-alternative forced choice (2AFC) task for intraoperative use. Behavioral responses were acquired using an Arduino based single-hand held joystick controller equipped with a 3-axis accelerometer, and two button presses, capable of sampling at 2 kHz. We include designs for all task relevant code, 3D printed components, and Arduino pin-out diagram.

They demonstrated feasibility both in and out of the operating room with behavioral results represented by three healthy control subjects and two Parkinson’s disease subjects undergoing deep brain stimulator implantation. Psychometric assessment of performance indicated that the subjects could detect, interpret and respond accurately to the task stimuli using the joystick controller. We also demonstrate, using intraoperative neurophysiology recorded during the task, that the behavioral system described here allows us to examine neural correlates of human behavior.

COMPARISON WITH EXISTING METHODS: For low cost and minimal effort, any clinical neural recording system can be adapted for intraoperative behavioral testing with our experimental setup.

CONCLUSION: Our system will enable clinicians and basic scientists to conduct intraoperative awake and behaving electrophysiologic studies in humans 2).

Indications

see Deep brain stimulation indications.

Targets

see Deep Brain Stimulation Targets.

Research has demonstrated that multi-target DBS shows some benefits over single target DBS.

Deep Brain Stimulation during Pregnancy and Delivery

Scelzo et al. report a retrospective case series of women, followed in two DBS centers, who became pregnant and went on to give birth to a child while suffering from disabling MD or psychiatric diseases [Parkinson’s disease, dystonia, Tourette’s syndrome (TS), Obsessive Compulsive Disorder (OCD)] treated by DBS. Clinical status, complications and management before, during, and after pregnancy are reported. Two illustrative cases are described in greater detail.

DBS improved motor and behavioral disorders in all patients and allowed reduction in, or even total interruption of disease-specific medication during pregnancy. With the exception of the spontaneous early abortion of one fetus in a twin pregnancy, all pregnancies were uneventful in terms of obstetric and pediatric management. DBS parameters were adjusted in five patients in order to limit clinical worsening during pregnancy. Implanted material limited breast-feeding in one patient because of local pain at submammal stimulator site and led to local discomfort related to stretching of the cable with increasing belly size in another patient whose stimulator was implanted in the abdominal wall.

Not only is it safe for young women with MD, TS and OCD who have a DBS-System implanted to become pregnant and give birth to a baby but DBS seems to be the key to becoming pregnant, having children, and thus greatly improves quality of life 3).

Technique

Deep brain stimulation technique.

see Short pulse deep brain stimulation.

Frameless deep brain stimulation

Postoperative evaluation

Recent developments in the postoperative evaluation of deep brain stimulation surgery on the group level warrant the detection of achieved electrode positions based on postoperative imaging. Computed tomography (CT) is a frequently used imaging modality, but because of its idiosyncrasies (high spatial accuracy at low soft tissue resolution), it has not been sufficient for the parallel determination of electrode position and details of the surrounding brain anatomy (nuclei). The common solution is rigid fusion of CT images and magnetic resonance (MR) images, which have much better soft tissue contrast and allow accurate normalization into template spaces. Here, we explored a deep-learning approach to directly relate positions (usually the lead position) in postoperative CT images to the native anatomy of the midbrain and group space.

Materials and methods: Deep learning is used to create derived tissue contrasts (white matter, gray matter, cerebrospinal fluid, brainstem nuclei) based on the CT image; that is, a convolution neural network (CNN) takes solely the raw CT image as input and outputs several tissue probability maps. The ground truth is based on coregistrations with MR contrasts. The tissue probability maps are then used to either rigidly coregister or normalize the CT image in a deformable way to group space. The CNN was trained in 220 patients and tested in a set of 80 patients.

Results: Rigorous validation of such an approach is difficult because of the lack of ground truth. We examined the agreements between the classical and proposed approaches and considered the spread of implantation locations across a group of identically implanted subjects, which serves as an indicator of the accuracy of the lead localization procedure. The proposed procedure agrees well with current magnetic resonance imaging-based techniques, and the spread is comparable or even lower.

Postoperative CT imaging alone is sufficient for accurate localization of the midbrain nuclei and normalization to the group space. In the context of group analysis, it seems sufficient to have a single postoperative CT image of good quality for inclusion. The proposed approach will allow researchers and clinicians to include cases that were not previously suitable for analysis 4).

Complications

see Deep brain stimulation complications.

Case series

Harmsen et al. assessed the state of DBS-related research by analyzing the DBS literature as well as active studies sponsored by the National Institutes of Health (NIH) or German Research Foundation (Deutsche Forschungsgemeinschaft [DFG]).In total, 8,974 publications, 172 active NIH-funded projects, and 34 active DFG projects were identified. Records spanned 52 different disorders across 31 distinct brain targets and showed a shift toward studies examining conditions other than movement disorders. Most published works involved human research (80.6% of published studies), of which 10.2% were identified as clinical trials. Increasingly, studies focused on imaging or electrophysiological changes associated with DBS (69.8% NIH-active and 70.6% DFG-active vs. 25.8% published) or developing new stimulation techniques and adaptive technologies (37.8% NIH-active and 17.6% DFG-active vs. 6.5% published).

This overview in 2022 of past and present DBS-related studies provides insight into the status of DBS research and what we can anticipate in the future concerning new indications, improved/novel target selection and stimulation paradigms, closed-loop technology, and a better understanding of the mechanisms of action of DBS 5).

see Deep Brain Stimulation case series

Case reports

A 79-year-old woman with a history of coarse tremors effectively managed with deep brain stimulation presented with multiple intracranial metastases from a newly diagnosed lung cancer and was referred for whole-brain radiation therapy. She was treated with a German helmet technique to a total dose of 30 Gy in 10 fractions using 6 MV photons via opposed lateral fields with the neurostimulator turned off prior to delivery of each fraction. The patient tolerated the treatment well with no acute complications and no apparent change in the functionality of her neurostimulator device or effect on her underlying neuromuscular disorder. This represents the first reported case of the safe delivery of whole-brain radiation therapy in a patient with an implanted neurostimulator device. In cases such as this, neurosurgeons and radiation oncologists should have discussions with patients about the risks of brain injury, device malfunction or failure of the device, and plans for rigorous testing of the device before and after radiation therapy 6).

Books

see Deep Brain Stimulation Books.

1)

Pollo C, Kaelin-Lang A, Oertel MF, Stieglitz L, Taub E, Fuhr P, Lozano AM, Raabe A, Schüpbach M. Directional deep brain stimulation: an intraoperative double-blind pilot study. Brain. 2014 Jul;137(Pt 7):2015-26. doi: 10.1093/brain/awu102. Epub 2014 May 19. PubMed PMID: 24844728.
2)

Tekriwal A, Felsen G, Thompson JA. Modular auditory decision-making behavioral task designed for intraoperative use in humans. J Neurosci Methods. 2018 May 7. pii: S0165-0270(18)30134-1. doi: 10.1016/j.jneumeth.2018.05.004. [Epub ahead of print] PubMed PMID: 29746889.
3)

Scelzo E, Mehrkens JH, Bötzel K, Krack P, Mendes A, Chabardès S, Polosan M, Seigneuret E, Moro E, Fraix V. Deep Brain Stimulation during Pregnancy and Delivery: Experience from a Series of “DBS Babies”. Front Neurol. 2015 Sep 1;6:191. doi: 10.3389/fneur.2015.00191. eCollection 2015. PubMed PMID: 26388833.
4)

Reisert M, Sajonz BEA, Brugger TS, Reinacher PC, Russe MF, Kellner E, Skibbe H, Coenen VA. Where Position Matters-Deep-Learning-Driven Normalization and Coregistration of Computed Tomography in the Postoperative Analysis of Deep Brain Stimulation. Neuromodulation. 2022 Nov 21:S1094-7159(22)01330-7. doi: 10.1016/j.neurom.2022.10.042. Epub ahead of print. PMID: 36424266.
5)

Harmsen IE, Wolff Fernandes F, Krauss JK, Lozano AM. Where Are We with Deep Brain Stimulation? A Review of Scientific Publications and Ongoing Research. Stereotact Funct Neurosurg. 2022 Feb 1:1-14. doi: 10.1159/000521372. Epub ahead of print. PMID: 35104819.
6)

Kotecha R, Berriochoa CA, Murphy ES, Machado AG, Chao ST, Suh JH, Stephans KL. Report of whole-brain radiation therapy in a patient with an implanted deep brain stimulator: important neurosurgical considerations and radiotherapy practice principles. J Neurosurg. 2016 Apr;124(4):966-70. doi: 10.3171/2015.2.JNS142951. Epub 2015 Aug 28. PubMed PMID: 26315009.

Tourette’s syndrome

Tourette’s syndrome

A disorder characterized by random, repeated, and stereotyped motor tic or vocal tics for over > 1 year, 1) usually in several “bouts” per day. Onset is before age 18 years (mean age: 5 years). Male: female ratio is 4:1. The tics may be socially inappropriate, as such, are disabling. TS is often associated with OCD, ADHD & other personality disorders.

The eponym was bestowed by Jean-Martin Charcot (1825–1893) on behalf of his resident, Georges Albert Édouard Brutus Gilles de la Tourette (1857–1904), a French physician and neurologist, who published an account of nine patients with Tourette’s in 1885.

Tourette’s was once considered a rare and bizarre syndrome, most often associated with the exclamation of obscene words or socially inappropriate and derogatory remarks (coprolalia), but this symptom is present in only a small minority of people with Tourette’s.

Tourette’s is no longer considered a rare condition, but it is not always correctly identified because most cases are mild and the severity of tics decreases for most children as they pass through adolescence. Between 0.4% and 3.8% of children ages 5 to 18 may have Tourette’s; the prevalence of other tic disorders in school-age children is higher, with the more common tics of eye blinking, coughing, throat clearing, sniffing, and facial movements. Extreme Tourette’s in adulthood is a rarity, and Tourette’s does not adversely affect intelligence or life expectancy.

Genetic and environmental factors play a role in the etiology of Tourette’s, but the exact causes are unknown. In most cases, medication is unnecessary. There is no effective treatment for every case of tics, but certain medications and therapies can help when their use is warranted. Education is an important part of any treatment plan, and explanation and reassurance alone are often sufficient treatment.

Comorbid conditions (co-occurring diagnoses other than Tourette’s) such as attention-deficit hyperactivity disorder (ADHD) and obsessive–compulsive disorder (OCD) are present in many patients seen in tertiary specialty clinics. These other conditions often cause more functional impairment to the individual than the tics that are the hallmark of Tourette’s; hence, it is important to correctly identify comorbid conditions and treat them.

Associations

Cavum septum pellucidum may also indicate disruption of neurodevelopment and has been associated with neurodevelopmental and psychiatric conditions including bipolar disorder, Tourette’s syndrome, obsessive-compulsive disorder, and schizophrenia, among others 2)

Clinical features

Tourette syndrome (also called Tourette’s syndrome, Tourette’s disorder, Gilles de la Tourette syndrome, GTS or, more commonly, simply Tourette’s or TS) is an inherited neuropsychiatric disorder with onset in childhood, characterized by multiple physical (motor) tics and at least one vocal (phonic) tic. These tics characteristically wax and wane, can be suppressed temporarily, and are preceded by a premonitory urge. Tourette’s is defined as part of a spectrum of tic disorders, which includes provisional, transient and persistent (chronic) tics.

Characterized by motor and vocal tics, which is often associated with psychiatric comorbidities. Dysfunction of basal ganglia pathways might account for the wide spectrum of symptoms in TS patients. Although psychiatric symptoms may be related to limbic networks, the specific contribution of different limbic structures remains unclear.

Temiz et al. used tractography to investigate cortical connectivity with the striatal area (caudate, putamen, core and shell of the nucleus accumbens), the subthalamic nucleus (STN), and the adjacent medial subthalamic region (MSR) in 58 TS patients and 35 healthy volunteers. 82% of TS patients showed psychiatric comorbidities, with significantly higher levels of anxiety and impulsivity compared to controls. Tractography analysis revealed significantly increased limbic cortical connectivity of the left MSR with the entorhinal cortex (BA34), insular cortex (BA48), and temporal cortex (BA38) in TS patients compared to controls. Furthermore, they found that left insular-STN connectivity was positively correlated with impulsivity scores for all subjects and with anxiety scores for all subjects, particularly for TS. The study highlights a heterogenous modification of limbic structure connectivity in TS, with specific abnormalities found for the subthalamic area. Abnormal connectivity with the insular cortex might underpin the higher level of impulsivity and anxiety observed in Tourette syndrome 3).

Treatment

see Tourette’s syndrome treatment.

Case series

Tourette’s syndrome case series.

Case reports

2018

Richieri et al., report the first case of a patient with severe, intractable Tourette Syndrome (TS) with comorbid Obsessive Compulsive disorder (OCD), who recovered from both disorders with gamma knife stereotactic radiosurgery following deep brain stimulation (DBS). This case highlights the possible role of the internal capsule within the neural circuitries underlying both TS and OCD, and suggests that in cases of treatment-refractory TS and comorbid OCD, bilateral anterior capsulotomy using stereotactic radiosurgery may be a viable treatment option 4).

1)

Kurlan R. Clinical practice. Tourette’s Syndrome. N Engl J Med. 2010; 363:2332–2338
2)

Silk T, Beare R, Crossley L, et al. Cavum septum pellucidum in pediatric traumatic brain injury. Psychiatry Res. 2013; 213:186–192
3)

Temiz G, Atkinson-Clement C, Lau B, Czernecki V, Bardinet E, Francois C, Worbe Y, Karachi C. Structural hyperconnectivity of the subthalamic area with limbic cortices underpins anxiety and impulsivity in Tourette syndrome. Cereb Cortex. 2022 Oct 30:bhac408. doi: 10.1093/cercor/bhac408. Epub ahead of print. PMID: 36310093.
4)

Richieri R, Blackman G, Musil R, Spatola G, Cavanna AE, Lançon C, Régis J. Positive clinical effects of gamma knife capsulotomy in a patient with deep brain stimulation-refractory Tourette Syndrome and Obsessive Compulsive Disorder. Clin Neurol Neurosurg. 2018 Apr 26;170:34-37. doi: 10.1016/j.clineuro.2018.04.018. [Epub ahead of print] PubMed PMID: 29723733.

Parkinson’s Disease Treatment Guidelines

Parkinson’s Disease Treatment Guidelines

An update of the Parkinson’s Disease treatment Guidelines was commissioned by the European Academy of Neurology and the European section of the Movement Disorder Society. Although these treatments are initiated usually in specialized centers, the general neurologist should know the therapies and their place in the treatment pathway.

Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to assess the spectrum of approved interventions including deep brain stimulation (DBS) or brain lesioning with different techniques (radiofrequency thermocoagulation, radiosurgery, magnetic resonance imaging-guided focused ultrasound surgery [MRgFUS] of the following targets: subthalamic nucleus [STN], ventrolateral thalamus, and pallidum internum [GPi]). Continuous delivery of medication subcutaneously (apomorphine pump) or through percutaneous ileostomy (Intrajejunal levodopa-carbidopa therapy) [LCIG]) was also included. Changes in motor features, health-related quality of life (QoL), adverse effects, and further outcome parameters were evaluated. Recommendations were based on high-class evidence and graded in three gradations. If only lower class evidence was available but the topic was felt to be of high importance, a clinical consensus of the guideline task force was gathered.

Two research questions have been answered with eight recommendations and five clinical consensus statements. Invasive therapies are reserved for specific patient groups and clinical situations mostly in the advanced stage of Parkinson’s disease (PD). Interventions may be considered only for special patient profiles, which are mentioned in the text. Therapy effects are reported as a change compared with current medical treatment. Subthalamic deep brain stimulation for Parkinson’s disease is the best-studied intervention for advanced disease with fluctuations not satisfactorily controlled with oral medications; it improves motor symptoms and QoL, and treatment should be offered to eligible patients. GPi-DBS can also be offered. For early PD with early fluctuations, STN-DBS is likely to improve motor symptoms, and QoL and can be offered. DBS should not be offered to people with early PD without fluctuations. LCIG and an apomorphine pump can be considered for advanced PD with fluctuations not sufficiently managed with oral treatments. Unilateral MRgFUS of the STN can be considered for distinctly unilateral PD within registries. The clinical consensus was reached on the following statements: Radiosurgery with gamma radiation cannot be recommended, unilateral radiofrequency thermocoagulation of the pallidum for advanced PD with treatment-resistant fluctuations, and unilateral radiofrequency thermocoagulation of the thalamus for resistant tremor can be recommended if other options are not available, unilateral MRgFUS of the thalamus for medication-resistant tremor of PD can be considered only within registries, and unilateral MRgFUS of the pallidum is not recommended.

Evidence for invasive therapies in PD is heterogeneous. Only some of these therapies have a strong scientific basis 1) 2).

European Academy of Neurology/Movement Disorder Society-European Section Guidelines on Pallidotomy for Parkinson’s Disease 3).

1)

Deuschl G, Antonini A, Costa J, Śmiłowska K, Berg D, Corvol JC, Fabbrini G, Ferreira J, Foltynie T, Mir P, Schrag A, Seppi K, Taba P, Ruzicka E, Selikhova M, Henschke N, Villanueva G, Moro E. European Academy of Neurology/Movement Disorder Society-European Section Guideline on the Treatment of Parkinson’s Disease: I. Invasive Therapies. Mov Disord. 2022 Jul;37(7):1360-1374. doi: 10.1002/mds.29066. Epub 2022 Jul 6. PMID: 35791767.
2)

Deuschl G, Antonini A, Costa J, Śmiłowska K, Berg D, Corvol JC, Fabbrini G, Ferreira J, Foltynie T, Mir P, Schrag A, Seppi K, Taba P, Ruzicka E, Selikhova M, Henschke N, Villanueva G, Moro E. European Academy of Neurology/Movement Disorder Society – European Section guideline on the treatment of Parkinson’s disease: I. Invasive therapies. Eur J Neurol. 2022 Sep;29(9):2580-2595. doi: 10.1111/ene.15386. Epub 2022 Jul 6. PMID: 35791766.
3)

Hariz M, Bronstein JM, Cosgrove GR, de Bie RMA, DeLong MR, Gross RE, Krack P, Krauss JK, Lang AE, Lees AJ, Lozano AM, Obeso JA, Schuurman PR, Vitek JL. European Academy of Neurology/Movement Disorder Society-European Section Guidelines on Pallidotomy for Parkinson’s Disease: Let’s Be Accurate. Mov Disord. 2022 Sep 1. doi: 10.1002/mds.29210. Epub ahead of print. PMID: 36047463.

Microvascular decompression for trigeminal neuralgia outcome

Microvascular decompression for trigeminal neuralgia outcome

Microvascular decompression (MVD) is the most effective long-term surgical treatment for trigeminal neuralgia (TN) patients. The risk factors for poor pain control following MVD surgery are not fully understood.

A significant proportion of patients with significant neurovascular compression fail to achieve long-term pain relief after technically successful surgery. Neuroimaging using magnetic resonance imaging (MRI) provides a non-invasive method to generate objective biomarkers of eventual response to TN surgery 1).

Younger patients with TN had worse long-term pain outcomes following MVD. Additional factors associated with postoperative recurrence included poor preoperative pain control (BNI score > IV) and multivessel compression. Furthermore, SCA combined with PV was confirmed to be associated with a worse outcome 2).

Not all patients with TN manifest unequivocal neurovascular compression (NVC). Furthermore, over time patients with an initially successful MVD manifest a relentless rate of TN recurrence.

It does not achieve 100 % cure rate. Re-exploration of the posterior fossa may carry increased risk over first-time MVD and is not always successful, so other treatments are needed.

Age itself does not seem to represent a major contraindication of microvascular decompression for typical trigeminal neuralgia 3).

Patients 60 yr of age and older have significantly better long-term pain outcomes following MVD than younger patients 4).

1)

Wang Z, Zhao Z, Song Z, Wang Y, Zhao Z. The application of magnetic resonance imaging (MRI) for the prediction of surgical outcomes in trigeminal neuralgia. Postgrad Med. 2022 May 3:1-7. doi: 10.1080/00325481.2022.2067612. Epub ahead of print. PMID: 35503235.
2)

Shi J, Qian Y, Han W, Dong B, Mao Y, Cao J, Guan W, Zhou Q. Risk factors for outcomes following microvascular decompression for trigeminal neuralgia. World Neurosurg. 2020 Jan 17. pii: S1878-8750(20)30100-5. doi: 10.1016/j.wneu.2020.01.082. [Epub ahead of print] PubMed PMID: 31958591.
3)

Mastronardi L, Caputi F, Rinaldi A, Cacciotti G, Roperto R, Scavo CG, Stati G, Sufianov A. Typical Trigeminal Neuralgia: Comparison of Results between Patients Older and Younger than 65 Operated on with Microvascular Decompression by Retrosigmoid Approach. J Neurol Surg A Cent Eur Neurosurg. 2019 Aug 29. doi: 10.1055/s-0039-1693126. [Epub ahead of print] PubMed PMID: 31466107.
4)

Bick SK, Huie D, Sneh G, Eskandar EN. Older Patients Have Better Pain Outcomes Following Microvascular Decompression for Trigeminal Neuralgia. Neurosurgery. 2019 Jan 1;84(1):116-122. doi: 10.1093/neuros/nyy011. PubMed PMID: 29562363.