Improvement of obsessive-compulsive disorder after pallidothalamic tractotomy for cervical dystonia.

A 30-year-old woman with tardive dystonia in the cervical region from long-term antipsychotic meds was treated with radiofrequency ablation of the right pallidothalamic tract in the fields of Forel. The patient showed improvement in both cervical dystonia and obsessive-compulsive disorder after the procedure, with 77.4% improvement in cervical dystonia and 86.7% improvement in obsessive-compulsive disorder. Although the treatment site in this case was intended to treat cervical dystonia, the lesion was located in the optimal stimulation network for both obsessive-compulsive disorder and cervical dystonia, suggesting that neuromodulation of this region could potentially treat both simultaneously.

Unilateral pallidothalamic tractotomy at Forel's field H1 for cervical dystonia.

BACKGROUND: Neurosurgical ablation of Forel's field H1 for cervical dystonia, which is currently abandoned, was formerly used in the 1960s-1970s. Regardless of the lack of neuroimaging modalities and objective evaluation scales, the reported efficacy was significant. Although recent studies have reappraised the ablation of the pallidothalamic tract at Forel's field H1 for Parkinson's disease, the efficacy for cervical dystonia has not been investigated well. METHODS: Data of 35 patients with cervical dystonia who underwent unilateral pallidothalamic tractotomy at Forel's field H1 were retrospectively analyzed. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) scores, the neck score of the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), and adverse events were evaluated preoperatively and at the last available follow-up period. RESULTS: The mean clinical follow-up period was 13.9 ± 6.5 months. The mean TWSTRS total scores were 34.3 ± 14.0 preoperatively and 18.4 ± 16.5 at the last available follow-up period (46.4% improvement, p < 0.0001). The BFMDRS neck score also improved significantly from 6.2 ± 2.9 preoperatively to 2.8 ± 2.8 at the last available follow-up period (55.0% improvement on the neck score, p < 0.0001). Reduced hand dexterity in seven patients, hypophonia in five patients, dysarthria in four patients, and executive dysfunction in one patient were confirmed as adverse events at the last available follow-up evaluation. One patient had postoperative hemorrhage. CONCLUSION: The current study confirmed significant improvement in TWSTRS total scores and BFMDRS neck scores at the 13.9-month follow-up after unilateral pallidothalamic tractotomy. The pallidothalamic tract in Forel's field H1 is expected to be an alternative treatment target for cervical dystonia.

Comorbid seizure reduction after pallidothalamic tractotomy for movement disorders: Revival of Jinnai's Forel-H-tomy.

Forel-H-tomy for intractable epilepsy was introduced by Dennosuke Jinnai in the 1960s. Recently, Forel-H-tomy was renamed to "pallidothalamic tractotomy" and revived for the treatment of Parkinson's disease and dystonia. Two of our patients with movement disorders and comorbid epilepsy experienced significant seizure reduction after pallidothalamic tractotomy, demonstrating the efficacy of this method. The first was a 29-year-old woman who had temporal lobe epilepsy with focal impaired awareness seizure once every three months and an aura 10-20 times daily, even with four antiseizure medicines. For the treatment of hand dyskinesia, she underwent left pallidothalamic tractotomy and her right-hand dyskinesia significantly improved. Fourteen months later, she had experienced no focal impaired awareness seizure and the aura decreased to one to three times per month. The second case was that of a 15-year-old boy diagnosed with progressive myoclonic epilepsy, who developed generalized tonic-clonic seizure, which manifested once every month, despite treatment with five antiseizure medicines. After surgery, myoclonic movements in his right hand slightly improved. A one-year follow-up revealed that he had not experienced a generalized tonic-clonic seizure. The lesion locations in the two cases were close to the vicinity of Jinnai's Forel-H-tomy. Forel's field H deserves reconsideration as a treatment target for intractable epilepsy.

Revisiting Forel Field Surgery.

BACKGROUND: Lesioning the Forel field or the subthalamic region is considered a possible treatment for tremoric patients with Parkinson disease, essential tremor, and other diseases. This surgical treatment was performed in the 1960s to 1970s and was an alternative to thalamotomy. Recently, there has been increasing interest in the reappraisal of stimulating and/or lesioning these targets, partly as a result of innovations in imaging and noninvasive ablative technologies, such as magnetic resonance-guided focused ultrasonography. OBJECTIVE: We wanted to perform a thorough review of the subthalamic region, both from an anatomic and a surgical standpoint, to offer a comprehensive and updated analysis of the techniques and results reported for patients with tremor treated with different techniques. METHODS: We performed a systematic review of the literature, gathering articles that included patients who underwent ablative or stimulation surgical techniques, targeting the pallidothalamic pathways (pallidothalamic tractotomy), cerebellothalamic pathway (cerebellothalamic tractotomy), or subthalamic area. RESULTS: Pallidothalamic tractotomy consists of a reduced area that includes pallidofugal pathways. It may be considered an interesting target, given the benefit/risk ratio and the clinical effect, which, compared with pallidotomy, involves a lower risk of injury or involvement of vital structures such as the internal capsule or optic tract. Cerebellothalamic tractotomy and/or posterior subthalamic area are other alternative targets to thalamic stimulation or ablative surgery. CONCLUSIONS: Based on the significant breakthrough that magnetic resonance-guided focused ultrasonography has meant in the neurosurgical world, some classic targets such as the pallidothalamic tract, Forel field, and posterior subthalamic area may be reconsidered as surgical alternatives for patients with movement disorders.

Pallidothalamic Tractotomy (Forel's Field H1-tomy) for Dystonia: Preliminary Results.

OBJECTIVES: The pallidothalamic tract connects the globus pallidus internus with the ventroanterior and ventrolateral parts of the thalamus. Lesioning or stimulation of the pallidothalamic tract has ameliorating effects on dyskinesia and dystonia in patients with Parkinson disease. However, the effect of the procedure on dystonia due to other etiologies has not been reported. METHODS: We retrospectively analyzed patients with dystonia who underwent unilateral pallidothalamic tractotomy between July 2017 and October 2018 at Tokyo Women's Medical University Hospital. The Burke-Fahn-Marsden Dystonia Rating Scale-Movement Scale was used to evaluate the severity of dystonia at three time points (before surgery, 3 months postoperatively, and the last available follow-up). Adverse events were also evaluated. RESULTS: Eleven patients underwent unilateral pallidothalamic tractotomy, including 5 with generalized dystonia, 4 with segmental dystonia, and 2 with focal (cervical) dystonia. All patients had undergone unilateral pallidotomy before contralateral pallidothalamic tractotomy. The mean interval between the previous surgery (pallidotomy) and pallidothalamic tractotomy was 9.5 ± 3.1 months. The mean follow-up period was 11.5 ± 4.2 months. The Burke-Fahn-Marsden Dystonia Rating Scale-Movement Scale scores at 3 months after pallidothalamic tractotomy (5.8 ± 8.4) and at the last available follow-up (5.6 ± 8.3, P < 0.001) were significantly improved compared with that before pallidothalamic tractotomy (21.8 ± 16.3). The most common adverse event was reduced voice volume (6 patients), which was mild and did not interfere with the patient's daily activities. CONCLUSIONS: This study suggests that pallidothalamic tractotomy can be an alternative treatment target for dystonia. A larger and longer prospective study is needed to elucidate the safety and efficacy of pallidothalamic tractotomy for dystonia.

Stereotactic Lesion in the Forel's Field H: A 2-Years Prospective Open-Label Study on Motor and Nonmotor Symptoms, Neuropsychological Functions, and Quality of Life in Parkinson Disease.

BACKGROUND: Stereotactic lesion in the Forel's field H (campotomy) was proposed in 1963 to treat Parkinson disease (PD) symptoms. Despite its rationale, very few data on this approach have emerged. Additionally, no study has assessed its effects on nonmotor symptoms, neuropsychological functions and quality of life. OBJECTIVE: To provide a prospective 2-yr assessment of motor, nonmotor, neuropsychological and quality of life variables after unilateral campotomy. METHODS: Twelve PD patients were prospectively evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS), the Dyskinesia Rating Scale and the Parkinson's disease quality of life questionnaire (PDQ39) before campotomy, and after 6 and 24 mo. Nonmotor, neuropsychiatric, neuropsychological and quality of life variables were assessed. The impact of PD on global health was also rated. RESULTS: A significant reduction in contralateral rest tremor (65.7%, P < .001), rigidity (87.8%, P < .001), bradykinesia (68%, P < .001) and axial symptoms (24.2%, P < .05) in offmedication condition led to a 43.9% reduction in UPSDRS III scores 2 yr after campotomy (P < .001). Gait improved by 31.9% (P < .05) and walking time to cover 7 m was reduced by 43.2% (P < .05). Pain decreased by 33.4% (P < .01), while neuropsychiatric and neuropsychological functions did not change. Quality of life improved by 37.8% (P < .05), in line with a 46.7% reduction of disease impact on global health (P < .001). CONCLUSION: A significant 2-yr improvement of motor symptoms, gait performance and pain was obtained after unilateral campotomy without significant changes to cognition. Quality of life markedly improved in parallel with a significant reduction of PD burden on global health.

Anatomical predictors of cognitive decline after subthalamic stimulation in Parkinson's disease.

We investigated whether pre-operative MRI measures of focal brain atrophy could predict cognitive decline occurring after deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson's disease (PD). For that purpose, we prospectively collected data of 42 consecutive patients with PD who underwent bilateral STN-DBS. Normalized brain structure volumes and cortical thicknesses were measured on pre-operative T1-weighted MRI. Patients were tested for their cognitive performances before surgery and 1 year after. After controlling for age, gender, pre-operative disease severity, change in dopaminomimetic dose after surgery and contact location, we found correlations: (1) between the variation of the total Mattis dementia rating scale (MDRS) score and left lateral ventricle volume (p = 0.032), (2) between the variation of the initiation/perseveration subscore of the MDRS and the left nucleus accumbens volume (p = 0.042) and the left lateral ventricle volume (p = 0.017) and (3) between the variation of the backward digit-span task and the right and left superior frontal gyrus thickness (p = 0.004 and p = 0.007, respectively). Left nucleus accumbens atrophy was associated with decline in the initiation/perseveration subscore with the largest effect size (d = - 1.64). Pre-operative left nucleus accumbens volume strongly predicted postoperative decline in the initiation/attention subscore (AUC = 0.92, p < 0.001, 96.3% sensitivity, 80.0% specificity, 92.9% PPV and 92.9% NPV). We conclude that the morphometric measures of brain atrophy usually associated with cognitive impairment in PD can also explain or predict a part of cognitive decline after bilateral STN-DBS. In particular, the left accumbens nucleus volume could be considered as a promising marker for guiding surgical decisions.

Subtalamotomía como neuroprotección en la enfermedad de Parkinson. El papel de los ultrasonidos guiados por resonancia como cirugía temprana / Neuroprotective subthalamotomy in Parkinson's disease. The role of magnetic resonance-guided focused ultrasound in early surgery

La hiperactividad del núcleo subtalámico en la enfermedad de Parkinson puede ser un fenómeno temprano. El comienzo de la misma no se conoce con exactitud pero podría ocurrir en la fase presintomática de la enfermedad. Esta hiperactividad glutamatérgica puede ser tóxica para las neuronas dopaminérgicas de la sustancia negra compacta. Si esto fuera así, el neurotransmisor excitador, ácido glutámico, afectaría a las neuronas que se encuentran con un turnover elevado como mecanismo compensador. ¿Podría una lesión en el núcleo subtalámico reducir esta hiperactividad y ser un mecanismo neuroprotector para dichas neuronas? Los autores hipotetizan sobre la posibilidad de realizar una cirugía sobre la lesión en el núcleo subtalámico en una fase muy temprana para evitar el efecto neurotóxico del ácido glutámico sobre las neuronas dopaminérgicas y ser una cirugía neuroprotectora que pudiera alterar la historia natural de la enfermedad en sus primeras fases motoras. En este sentido, los ultrasonidos guiados por resonancia abren una nueva ventana en el arsenal estereotáctico

Subthalamic nucleus hyperactivity in Parkinson's disease may be a very early phenomenon. Its start is not well known, and it may occur during the pre-symptomatic disease stage. Glutamatergic hyperactivity may be neurotoxic over the substantia nigra compacta dopaminergic neurons. If this occurred, the excitatory neurotransmitter, glutamate, should affect the neurons that maintain a high turnover as a compensatory mechanism. Would a subthalamic nucleus lesion decrease this hyperactivity and thus be considered as a neuroprotective mechanism for dopaminergic neurons? The authors hypothesise about the possibility to perform surgery on a subthalamic nucleus lesion at a very early stage in order to avoid the neurotoxic glutamatergic effect over the dopaminergic neurons, and therefore be considered as a neuroprotective surgery able to alter the progress of the disease during early motor symptoms. In this regard, magnetic resonance-guided focused ultrasound techniques open a new window in the stereotactic armamentarium

Subthalamotomy-induced changes in dopamine receptors in parkinsonian monkeys.

Subthalamotomy allows a reduction of doses of l-DOPA in dyskinetic patients while its antiparkinsonian benefits are preserved. However, the mechanisms of the potentiation of this response to medication remain to be elucidated. Hence, dopamine D1 and D2 receptors as well as the dopamine transporter were investigated using receptor binding autoradiography. D1 and D2 receptors as well as preproenkephalin and preprodynorphin mRNA levels were measured by in situ hybridization. Four dyskinetic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) parkinsonian monkeys that underwent unilateral subthalamotomy were compared to four controls, four saline-treated and four l-DOPA-treated MPTP monkeys. Dopamine, its metabolites and its transporter were extensively and similarly decreased in all parkinsonian monkeys. D1 receptor specific binding was decreased in the striatum of all MPTP monkeys. The l-DOPA-induced decrease in D1 receptor specific binding was reversed in the striatum ipsilateral to subthalamotomy. D1 receptor mRNA levels followed a similar pattern. D2 receptor specific binding and mRNA levels remained unchanged in all groups. Striatal preproenkephalin mRNA levels were overall increased in MPTP monkeys; the STN-lesioned parkinsonian group had significantly lower values than the saline-treated and l-DOPA-treated parkinsonian monkeys in the dorsolateral putamen. Striatal preprodynorphin mRNA levels remained unchanged in MPTP monkeys compared to controls whereas it increased in all monkeys treated with l-DOPA compared to controls; subthalamotomy induced a decrease in the dorsolateral putamen ipsilateral to surgery. The improved motor response to l-DOPA after subthalamotomy in the parkinsonian monkeys investigated may be associated with an increased synthesis and expression of D1 receptors ipsilateral to STN lesion of the direct pathway.

Individualized current-shaping reduces DBS-induced dysarthria in patients with essential tremor.

OBJECTIVE: To investigate in patients with essential tremor (ET) treated with thalamic/subthalamic deep brain stimulation (DBS) whether stimulation-induced dysarthria (SID) can be diminished by individualized current-shaping with interleaving stimulation (cs-ILS) while maintaining tremor suppression (TS). METHODS: Of 26 patients screened, 10 reported SID and were invited for testing. TS was assessed by the Tremor Rating Scale and kinematic analysis of postural and action tremor. SID was assessed by phonetic and logopedic means. Additionally, patients rated their dysarthria on a visual analog scale. RESULTS: In 6 of the 10 patients with ET, DBS-ON (relative to DBS-OFF) led to SID while tremor was successfully reduced. When comparing individualized cs-ILS with a non-current-shaped interleaving stimulation (ILS) in these patients, there was no difference in TS while 4 of the 6 patients showed subjective improvement of speech during cs-ILS. Phonetic analysis (ILS vs cs-ILS) revealed that during cs-ILS there was a reduction of voicing during the production of voiceless stop consonants and also a trend toward an improvement in oral diadochokinetic rate, reflecting less dysarthria. Logopedic rating showed a trend toward deterioration in the diadochokinesis task when comparing ON with OFF but no difference between ILS and cs-ILS. CONCLUSION: This is a proof-of-principle evaluation of current-shaping in patients with ET treated with thalamic/subthalamic DBS and experiencing SID. Data suggest a benefit on SID from individual shaping of current spread while TS is preserved. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that in patients with ET treated with DBS with SID, individualized cs-ILS reduces dysarthria while maintaining tremor control.

Evolution and rebirth of functional stereotaxy in the subthalamus.

The first human stereotactic surgery based on intracerebral landmarks and Cartesian coordinates was performed in 1947. With this followed the publication of a number of stereotactic frames and atlases. The intercommissural line joining the anterior and posterior commissures was to define stereotactic coordinate systems used in movement disorders and other functional neurosurgical procedures. Initially the target for Parkinson disease was the globus pallidus internus (GPi), but many investigators soon turned to the thalamus or parts of the subthalamus, but not the subthalamic nucleus. Microelectrode recording was introduced in 1961. With the apparent clinical efficacy of L-DOPA in 1965 interest in stereotactic surgery for Parkinson disease declined. The failure of prolonged, consistent pharmacologic management of bradykinesia and tremor, the side effects of dyskinesias, and the fading therapeutic success of medical treatment of movement disorders led to a resurgence of interest in the surgical management of movement disorders. With advances in understanding of the functional anatomy of the corticobasal ganglia circuit, advances in brain imaging, more sophisticated electrophysiologic recordings, and the use of deep brain stimulation as a reversible lesion, stereotactic surgery returned as a viable option for the treatment of movement disorders. The posterior medial part of the globus pallidus, ventral intermediate nucleus of the thalamus, and the subthalamus, its nuclei and pathways, are sites for interrupting pathophysiologic circuits. Not only has this been applied to movement disorders, but to epilepsy, chronic pain, and behavioral disorders.

Unilateral caudal zona incerta deep brain stimulation for Parkinsonian tremor.

BACKGROUND: The subthalamic nucleus is currently the target of choice in deep brain stimulation (DBS) for Parkinson's disease (PD), while thalamic DBS is used in some cases of tremor-dominant PD. Recently, a number of studies have presented promising results from DBS in the posterior subthalamic area, including the caudal zona incerta (cZi). The aim of the current study was to evaluate cZi DBS in tremor-dominant Parkinson's disease. METHODS: 14 patients with predominately unilateral tremor-dominant PD and insufficient relief from pharmacologic therapy were included and evaluated according to the motor part of the Unified Parkinson Disease Rating Scale (UPDRS). The mean age was 65 ± 6.1 years and the disease duration 7 ± 5.7 years. Thirteen patients were operated on with unilateral cZi DBS and 1 patient with a bilateral staged procedure. Five patients had non-L-dopa responsive symptoms. The patients were evaluated on/off medication before surgery and on/off medication and stimulation after a minimum of 12 months after surgery. RESULTS: At the follow-up after a mean of 18.1 months stimulation in the off-medication state improved the contralateral UPDRS III score by 47.7%. Contralateral tremor, rigidity, and bradykinesia were improved by 82.2%, 34.3%, and 26.7%, respectively. Stimulation alone abolished tremor at rest in 10 (66.7%) and action tremor in 8 (53.3%) of the patients. CONCLUSION: Unilateral cZi DBS seems to be safe and effective for patients with severe Parkinsonian tremor. The effects on rigidity and bradykinesia were, however, not as profound as in previous reports of DBS in this area.

Reoperation after failed deep brain stimulation for essential tremor.

OBJECTIVE: To evaluate the effects of reoperation with deep brain stimulation (DBS) in the caudal zona incerta (cZi) in patients with failed DBS in the ventral intermediate (Vim) nucleus of the thalamus for essential tremor. METHODS: The results of reoperation with cZi DBS in five patients with failed Vim DBS were retrospectively analyzed. RESULTS: Two patients had early failure of Vim DBS, and three after several years of good effect. The mean deviation from the atlas Vim target point was 1.4 mm. Before the reoperation Vim DBS improved hand function and tremor in the treated hand at 25 %, whereas cZi DBS achieved an improvement of 57%. Although cZi was more efficient than Vim DBS, also in the patients with late failure of Vim DBS, they still exhibited a considerable residual tremor on cZi DBS. CONCLUSIONS: The effect on tremor was, in this small sample population, improved by implanting an electrode in the cZi. The effect was modest in those patients suffering a deterioration years after the initial operation.

Visualisation of the zona incerta for deep brain stimulation at 3.0 Tesla.

PURPOSE: Deep-brain stimulation (DBS) of the zona incerta (ZI) has shown promising results for medication-refractory neurological disorders including Parkinson's disease (PD) and essential tremor (ET). The success of the intervention is indispensably dependent on the reliable visualisation of the ZI. The aim of the study was to evaluate different promising new magnetic resonance imaging (MRI) methods at 3.0 Tesla for pre-stereotactic visualisation of the ZI using a standard installation the protocol. METHODS: MRI of nine healthy volunteers was acquired (T1-MPRAGE, T2-FLAIR, T2*-FLASH2D, T2-SPACE and susceptibility-weighted imaging (SWI). Image quality and visualisation of the ZI for each sequence were analysed independently by two neuroradiologists using a 6-point scale. For T2*-FLASH2D the axial, coronal and sagittal planes were compared. The delineation of the ZI versus the internal capsule, the subthalamic nucleus and the pallidofugal fibres was evaluated in all sequences and compared to T2-FLAIR using a paired t-test. Inter-rater reliability, contrast-to-noise ratios (CNR), and signal-to-noise ratios (SNR) for the ZI were computed. For illustration, coronal T2*-FLASH2D images were co-registered with the corresponding section schema of the Schaltenbrand-Wahren stereotactic atlas. RESULTS: Only the rostral part of the ZI (rZI) could be identified. The rZI was best and reliably visualised in T2*-FLASH2D (particularly coronal orientation; p < 0.05). No major artifacts in the rZI were observed in any of the sequences. SWI, T2-SPACE, and T2*-FLASH imaging offered significant higher CNR values for the rZI compared to T2-FLAIR imaging using standard parameters. The co-registration of the coronal T2*-FLASH2D images projected the ZI clearly into the boundaries of the anatomical sections. CONCLUSIONS: The delineation of the rZI is best possible in T2*-FLASH2D (particularly coronal view) using a standard installation protocol at 3.0 T. The caudal ZI could not be discerned in any of the sequences.

Quality of life following DBS in the caudal zona incerta in patients with essential tremor.

BACKGROUND: Essential tremor (ET) is the most common movement disorder and often affects the quality of life. There are only a few studies evaluating the quality of life after deep brain stimulation (DBS). FINDINGS: This is a prospective study of 16 patients undergoing deep brain stimulation in the caudal Zona incerta (cZi). The quality of life was assessed with Quality of Life in Essential Tremor Questionnaire (QUEST) and SF-36 scores, and the tremor was evaluated using the essential tremor rating scale (ETRS). RESULTS: In the tremor rating, hand tremor on the treated side improved by 95%, hand function by 78% and activities of daily living by 71%. The QUEST score showed statistically significant improvements in the psychosocial and activities of daily living subscores. The SF-36 score did not show any significant improvement. CONCLUSIONS: Although very good tremor reduction was achieved, the improvement in the quality of life scores was more modest. This could partly be explained by the quality of life being affected by other factors than the tremor itself.

Deep brain stimulation of the subthalamic nucleus versus the zona incerta in the treatment of essential tremor.

BACKGROUND: Deep brain stimulation (DBS) is an effective treatment for essential tremor (ET). Currently the ventrolateral thalamus is the target of choice, but the posterior subthalamic area (PSA), including the caudal zona incerta (cZi), has demonstrated promising results, and the subthalamic nucleus (STN) has been suggested as a third alternative. The objective of the current study was to evaluate the effect of STN DBS in ET and to compare this to cZi DBS. METHODS: Four patients with ET were implanted with two ipsilateral electrodes, one in the STN and one in the cZi. All contacts were evaluated concerning the acute effect on tremor, and the effect of chronic DBS in either target was analyzed. RESULTS: STN and cZi both proved to be potent targets for DBS in ET. DBS in the cZi was more efficient, since the same degree of tremor reduction could here be achieved at lower energy consumption. Three patients became tremor-free in the treated hand with either STN or cZi DBS, while the fourth had a minor residual tremor after stimulation in either target. CONCLUSION: In this limited material, STN DBS was demonstrated to be an efficient treatment for ET, even though cZi DBS was more efficient. The STN may be an alternative target in the treatment of ET, pending further investigations to decide on the relative merits of the different targets.