Temporal lobe epilepsy

Temporal lobe epilepsy

Mesial temporal sclerosis (MTS) is the most common cause of intractable 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 deficitanxiety and depression.

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

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 epilepsyseizure 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.

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 tremorrigidity, postural abnormalities, and bradykinesia.

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

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

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

UPDRS

Parkinson’s Disease Epidemiology.

see Parkinson’s disease etiology.

Parkinson’s disease Pathogenesis.

see Parkinson’s disease pathophysiology.

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)

see Parkinson’s disease clinical features.

Parkinson’s disease diagnosis.

see Parkinson’s disease treatment.

Parkinson’s disease outcome

Parkinson’s disease complications

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 8)

see Parkinson’s disease case series.

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)

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.

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.

Bilateral anterior cingulotomy has been used to treat chronic painobsessive-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).

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)


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.
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