What is the primary status of DBS as a treatment for Alcohol Use Disorder (AUD)? a) It is a standard and FDA-approved treatment for AUD. b) It is experimental and emerging, with ongoing research and clinical trials. c) It is widely available and accessible. d) It is a widely used alternative to medications. Which brain region has been commonly targeted in DBS for AUD due to its role in addiction? a) Prefrontal cortex b) Hippocampus c) Nucleus accumbens d) Cerebellum What is the believed mechanism of action of DBS for AUD? a) Modulating neural circuits involved in motor control b) Modulating neural circuits involved in memory processing c) Modulating neural circuits involved in reward processing and craving d) Modulating neural circuits involved in visual perception What type of patients are typically considered for DBS for AUD? a) Individuals with mild alcohol addiction b) Individuals who have not responded to other therapies but have not severe addiction c) Patients with severe and treatment-resistant alcohol addiction d) Patients with a history of addiction to other substances What does the DBS procedure involve? a) Implanting electrodes in the heart b) Implanting electrodes in the eyes c) Implanting electrodes in the target brain region connected to a pulse generator d) Implanting electrodes in the liver What are some potential risks associated with DBS for AUD? a) Hair loss and skin discoloration b) Mood changes, cognitive changes, and physical symptoms c) Improved memory and concentration d) Enhanced athletic performance How does the effectiveness of DBS for AUD vary among individuals? a) It has a consistent and high success rate in all cases. b) It is equally effective for all stages of AUD. c) It varies among individuals, with some showing promising results and others less successful. d) It only works for young individuals. What ethical questions are raised by the use of DBS for AUD? a) Questions about the patient's age and gender b) Questions about the potential for altering behavior through brain manipulation, patient autonomy, and consent c) Questions about the cost of the procedure d) Questions about the potential for addiction to DBS What is the primary status of DBS for AUD in terms of cost and accessibility? a) It is widely available and affordable. b) It is a standard procedure covered by most insurance plans. c) It is complex and costly, typically reserved for research settings and specialized centers. d) It is free of charge for all patients. What does FDG-PET measure in the context of DBS for AUD? a) Brain structure b) Glucose metabolism in the nucleus accumbens c) Alcohol content in the bloodstream d) Electrical activity in the brain
Latest Pubmed Related Articles
Typical trigeminal neuralgia caused by microvascular compression of the trigeminal nerve root in the posterior fossa may become transformed over time into atypical trigeminal neuralgia, if left untreated. This transformation involves change in the character of pain and development of sensory impairment. Two representative cases are presented to support this theory.
If the theory of progressive change in character of pain and degree of sensory impairment in the course of otherwise typical trigeminal neuralgia is correct, trigeminal neuralgia, atypical neuralgia, and trigeminal neuropathic pain may represent different degrees of injury to the trigeminal nerve, therefore comprising a continuous spectrum rather than discrete diagnoses 2).
Slavin KV. Commentary: Development and Evaluation of a Preoperative Trigeminal Neuralgia Scoring System to Predict Long-Term Outcome Following Microvascular Decompression. Neurosurgery. 2019 Dec 9. pii: nyz540. doi: 10.1093/neuros/nyz540. [Epub ahead of print] PubMed PMID: 31813971.
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).
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
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
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)
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).
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)
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).
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)
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).
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).
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).
“5–5-5” incision (5mm medial, extending 5cm up to 5cm down), used for approach to seventh/ eighth nerve complex:
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).
Transposition in microvascular decompression for hemifacial spasm
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.
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).
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)
Temporal lobe epilepsy
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.
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
Neocortical temporal lobe epilepsy
Unilateral temporal lobe epilepsy
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).
Bilateral anterior cingulotomy
Lesioning of the target area is typically performed using bilateral stereotactic electrode placement and target ablation, which involves transparenchymal access through both hemispheres.
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).
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).
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).
by Ernest. Feigenbaum (Author)
Deep brain stimulation (DBS)
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).
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).
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).
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).
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).
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.
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)
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).
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).