Tics emergencies and malignant tourette syndrome: Assessment and management.

Tourette syndrome (TS) is a complex neurodevelopmental disorder characterized by the presence of tics, frequently accompanied by a variety of neuropsychiatric comorbidities. A subset of patients with TS present with severe and disabling symptoms, requiring prompt therapeutic intervention. Some of these manifestations may result in medical emergencies when severe motor or phonic tics lead to damage of anatomical structures closely related to the tic. Examples include myelopathy or radiculopathy following severe neck ("whiplash") jerks or a variety of self-inflicted injuries. In addition to self-aggression or, less commonly, allo-aggression, some patients exhibit highly inappropriate behavior, suicidal tendencies, and rage attacks which increase the burden of the disease and are important components of "malignant TS". This subset of TS is frequently associated with comorbid obsessive-compulsive disorder. Therapeutic measures include intensive behavioral therapy, optimization of oral pharmacotherapy, botulinum toxin injections, and deep brain stimulation.

Responsive deep brain stimulation for the treatment of Tourette syndrome.

To report the results of 'responsive' deep brain stimulation (DBS) for Tourette syndrome (TS) in a National Institutes of Health funded experimental cohort. The use of 'brain derived physiology' as a method to trigger DBS devices to deliver trains of electrical stimulation is a proposed approach to address the paroxysmal motor and vocal tic symptoms which appear as part of TS. Ten subjects underwent bilateral staged DBS surgery and each was implanted with bilateral centromedian thalamic (CM) region DBS leads and bilateral M1 region cortical strips. A series of identical experiments and data collections were conducted on three groups of consecutively recruited subjects. Group 1 (n = 2) underwent acute responsive DBS using deep and superficial leads. Group 2 (n = 4) underwent chronic responsive DBS using deep and superficial leads. Group 3 (n = 4) underwent responsive DBS using only the deep leads. The primary outcome measure for each of the 8 subjects with chronic responsive DBS was calculated as the pre-operative baseline Yale Global Tic Severity Scale (YGTSS) motor subscore compared to the 6 month embedded responsive DBS setting. A responder for the study was defined as any subject manifesting a ≥ 30 points improvement on the YGTSS motor subscale. The videotaped Modified Rush Tic Rating Scale (MRVTRS) was a secondary outcome. Outcomes were collected at 6 months across three different device states: no stimulation, conventional open-loop stimulation, and embedded responsive stimulation. The experience programming each of the groups and the methods applied for programming were captured. There were 10 medication refractory TS subjects enrolled in the study (5 male and 5 female) and 4/8 (50%) in the chronic responsive eligible cohort met the primary outcome manifesting a reduction of the YGTSS motor scale of ≥ 30% when on responsive DBS settings. Proof of concept for the use of responsive stimulation was observed in all three groups (acute responsive, cortically triggered and deep DBS leads only). The responsive approach was safe and well tolerated. TS power spectral changes associated with tics occurred consistently in the low frequency 2-10 Hz delta-theta-low alpha oscillation range. The study highlighted the variety of programming strategies which were employed to achieve responsive DBS and those used to overcome stimulation induced artifacts. Proof of concept was also established for a single DBS lead triggering bi-hemispheric delivery of therapeutic stimulation. Responsive DBS was applied to treat TS related motor and vocal tics through the application of three different experimental paradigms. The approach was safe and effective in a subset of individuals. The use of different devices in this study was not aimed at making between device comparisons, but rather, the study was adapted to the current state of the art in technology. Overall, four of the chronic responsive eligible subjects met the primary outcome variable for clinical effectiveness. Cortical physiology was used to trigger responsive DBS when therapy was limited by stimulation induced artifacts.

Precision Mapping of Thalamic Deep Brain Stimulation Lead Positions Associated With the Microlesion Effect in Tourette Syndrome.

BACKGROUND: The microlesion effect refers to the improvement of clinical symptoms after deep brain stimulation (DBS) lead placement and is suggested to indicate optimal lead placement. Very few studies have reported its implications in neuropsychiatric disorders. OBJECTIVE: To evaluate the magnitude of the microlesion effect in Tourette syndrome and the relationship between the microlesion effect and the anatomic location of implanted DBS leads. METHODS: Six male patients were included. Their median age at surgery and follow-up period were 25 years (range, 18-47) and 12 months (range, 6-24), respectively. All patients were videotaped pre- and postoperatively, and tic frequencies were counted. We also analyzed the precision of lead placement and evaluated the normative connectome associated with the microlesion area. RESULTS: The microlesion effect was observed as an improvement in tic symptoms in all patients, and the long-term clinical outcomes were favorable. The median motor tic frequency was 20.2 tics/min (range, 9.7-60) at baseline and decreased to 3.2 tics/min (1.2-11.3) in patients on postoperative day 1 ( P = .043) and to 5.7 tics/min (range, 1.9-16.6) in patients on postoperative day 7 ( P = .028). Phonic tic tended to improve immediately after surgery although the changes were not significant. Image analyses revealed that the precise position of the electrode was directed toward the anteromedial centromedian nucleus. Normative connectome analysis demonstrated connections between improvement-related areas and wide areas of the prefrontal cortex. CONCLUSION: This study shows that the microlesion effect may seem as an immediate improvement after optimal DBS lead placement in patients with Tourette syndrome.

Skin-related complications following deep brain stimulation surgery: A single-center retrospective analysis of 525 patients who underwent DBS surgery.

BACKGROUND: Although Deep Brain Stimulation (DBS) is a safe and proven treatment modality for patients suffering from debilitating movement and neuropsychiatric disorders, it is not free from complications. Management of skin erosion and infection following DBS surgery constitutes a challenge in everyday clinical practice. OBJECTIVES: Skin-related complications were evaluated in patients who underwent DBS surgery due to Parkinson's disease (PD), dystonia, essential tremor (ET), and other indications including Tourette syndrome (TS), Obsessive-Compulsive Disorder (OCD), and epilepsy. METHODS: A retrospective analysis of clinical data was performed on patients who underwent DBS surgery between November 2008 and September 2021 at the Department of Neurosurgery, Institute of Psychiatry and Neurology, Warsaw. RESULTS: 525 patients who underwent 927 DBS leads implantations were included in the analysis. There were 398 patients with PD, 80 with dystonia, 26 with ET, 7 with drug-resistant epilepsy, 5 with Multiple Sclerosis, 4 with Holme's or cerebellar tremor, 3 with TS, and 2 with OCD. 42 patients (8,0%) had 78 skin infection episodes. The overall level of skin erosion was 3,8% (20/525 patients). The risk of developing infection episode was connected with younger age at diagnosis (p = 0.017) and at surgery (p = 0.023), whereas the development of skin erosion was connected with the dystonia diagnosis (p = 0.012). Patients with dystonia showed the highest rate of infections and erosions (11/70 and 7/70 patients retrospectively). DISCUSSION: Postoperative skin complications are a serious side effect of DBS surgery. CONCLUSION: Our study suggests that dystonic patients are at higher risk of developing skin-related complications after DBS surgery.

Tourette's Syndrome cervical dystonia induced occipital neuralgia remedied by peripheral nerve stimulation: A case report / Síndrome de Tourette, distonia cervical induzida por neuralgia occipital remediada por estimulação nervosa periférica: relato de caso

BACKGROUND: Dystonia is uncommon in Tourette's syndrome, and occipital neuralgia secondary to Tourette's dystonia is more rare, affecting quality of life. Occipital peripheral nerve stimulation (PNS) is an excellent alternative by being adjustable and minimally invasive. Our case demonstrates occipital PNS as an effective option for refractory Tourette's dystonia. CASE PRESENTATION: A thirty-four-year-old male with poorly controlled Tourette's cervical dystonia presented with severe occipital neuralgia. Various medications were prescribed including propranolol and amitriptyline, and bilateral third-occipital nerve rhizotomies and occipital nerve blocks were trialed. Distal nerve blocks at the occipital protuberance were most effective. Therefore, an occipital PNS trial was done, and a PNS was implanted with no complications. Upon follow-up, the patient reported drastic pain reduction. CONCLUSION: Our case illustrates neuromodulation benefits for a rare presentation of refractory occipital neuralgia secondary to Tourette's-related dystonia. Occipital PNS should be considered for refractory cases because it is safe, easy to implant, and effective.

FUNDAMENTO: A distonia é incomum na síndrome de Tourette, e a neuralgia occipital secundária à distonia de Tourette é mais rara, afetando a qualidade de vida. A estimulação do nervo periférico occipital (SNP) é uma excelente alternativa por ser ajustável e minimamente invasiva. Nosso caso demonstra o SNP occipital como uma opção eficaz para a distonia de Tourette refratária. APRESENTAÇÃO DO CASO: Um homem de 34 anos com distonia cervical de Tourette mal controlada apresentou neuralgia occipital grave. Vários medicamentos foram prescritos, incluindo propranolol e amitriptilina, e foram testadas rizotomias bilaterais do nervo terceiro-occipital e bloqueios do nervo occipital. Os bloqueios dos nervos distais na protuberância occipital foram mais eficazes. Portanto, foi feito um ensaio de PNS occipital e um PNS foi implantado sem complicações. Após o acompanhamento, o paciente relatou redução drástica da dor. CONCLUSÃO: Nosso caso ilustra os benefícios da neuromodulação para uma apresentação rara de neuralgia occipital refratária secundária à distonia relacionada a Tourette. O PNS occipital deve ser considerado para casos refratários porque é seguro, fácil de implantar e eficaz.

What makes tics tick? Insights into Tourette syndrome.

This issue of Biomedical Journal provides the reader with articles concerning the latest understanding of Tourette syndrome (TS), the relation to genetic predisposition, defects in the dopaminergic system, and related comorbidities which further complications like sleep disruption. Treatment approaches for TS, attention deficit hyperactivity disorder and developmental coordination disorder are discussed. The second section of this issue offers insights into inside out integrin activation and its link to T cell activation, demonstrates how polarity in immune cells allows adoption to specialized functions, and describes the endosomal signaling of internalized T cell receptors (TCRs). The link between mutations in TCR signaling and immunodeficiencies is elucidated, as well as the interactions of thymocyte-expressed molecule involved in selection in T cell development. Additionally, we learn about a potential biomarker for colorectal cancer, screening tools for determining frailty in older adults, surgical approaches in spinal metastases, the influence of autophagy on mating behavior, and the effect of nitrite administration on SNARE proteins associated with insulin secretion. Finally, parameters for surgery in breast cancer are discussed, as well as gender and age dependent pain perception in a lysosomal storage disease, and the use of laser meridian massage in opioid use disorder. Three letters complement this issue, one concerning neuroimaging in pediatric COVID-19 patients, and two discussing the role of cancer antigen-125 and renal impairment in ovarian cancer patients.

Corneal collagen cross-linking for management of keratoconus in patients affected by Tourette syndrome.

PURPOSE: To present a series of two patients affected by Tourette syndrome (TS) and progressive keratoconus. CASE SERIES: Two young male patients with keratoconus and TS were referred to our center. In both patients eye rubbing was present and in one patient, an ocular tic was present determining blepharospasm. Progression of keratoconus occurred in both cases and corneal collagen cross-linking (CXL) was performed. All treated eyes showed topographic stability with stable refraction and conserved visual acuity, with a follow-up period ranging from 1.5 to 2.5 years. CONCLUSION: Patients with keratoconus and TS should be observed frequently to document topographical and refractive changes, and in case of progressing disease, CXL should be performed in order to prevent further progression.

Anterior Limb of Internal Capsule and Bed Nucleus of Stria Terminalis Stimulation for Gilles de la Tourette Syndrome with Obsessive-Compulsive Disorder in Adolescence: A Case of Success.

Gilles de la Tourette syndrome (GTS) is a neurobehavioral disorder comprising motor and vocal tics. In most cases it is associated with other disorders such as obsessive-compulsive disorder (OCD). In refractory cases deep brain stimulation (DBS) is a valid treatment option. This paper describes the case of a 15-year-old adolescent with an extremely refractory GTS with associated OCD. The patient developed catatonia associated with OCD, which partially remitted after electroconvulsive therapy. At the peak of the disease the Yale Global Tic Severity Scale (YGTSS) was 100 and the patient required sedation and intubation. All medical treatment options were unsuccessful. Bilateral DBS of the anterior limb of internal capsule (ALIC)/bed nucleus of stria terminalis (BST) region was performed, using a target below the BST and a trajectory through the ALIC, with stimulation of contacts 0 and 3. Two weeks after surgery sedatives were suspended and the patient was successfully extubated. One year after surgery the patient reached a YGTSS of 19, representing an 81% improvement. OCD completely resolved. Adverse events were a superficial infection and weight gain. In conclusion, this ALIC/BST stimulation appears to have been an effective and safe treatment for GTS with OCD in this case. Young age should not be an exclusion criterion for DBS in severe GTS and OCD. Further studies should be pursued for this target.

Rhynchophylline Attenuates Tourette Syndrome via BDNF/NF-κB Pathway In Vivo and In Vitro.

Tourette syndrome (TS) is characterized by one of the chronic neuropsychiatric disorders in multiple children, and the pathogenesis of Tourette syndrome (TS) has not been previously elucidated.The aim of this study was designed to investigate the effects of rhynchophylline (RH) on Tourette syndrome (TS) in rats.TS model was established in rats and BV2 cells by the selective 5-HT2A/2C agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). Behavior evaluations including stereotypy recording and autonomic activity test were performed. Inflammatory cytokine levels such as interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in serum, striatum, and cell supernatant were detected. The expression levels of BDNF/NF-κB pathway in striatum and BV2 cells were measured by Western blot. Dopamine (DA) and dopamine receptor D 2 (D2) in striatum were also measured.Data indicated that RH significantly decreased IL-6, IL-1ß, and TNF-α in serum, striatum, and cell supernatant of TS model, with altered expression of P-NF-κBp65, P-IκBα, and BDNF in TS rats, and DOI-induced BV2 cells, as evidenced by Western blot analysis and immunohistochemistry analysis. RH also significantly reduced the levels of DA and D2 in striatum.Our results shown that the regulation of BDNF/NF-κB pathway might be involved in the effects of RH on TS model.

Caracterización cognitiva del trastorno de Tourette con comorbilidad TDAH: un estudio de caso / Cognitive characterization of Tourette disorder with ADHD comorbidity: a case study

El trastorno de Tourette (TT) es un trastorno del neurodesarrollo que aparece en la primera infancia caracterizado por la presencia de tics fónicos y motores que dificultan la socialización y el proceso de aprendizaje escolar. El TT posee una variada comorbilidad que incluye el trastorno por déficit de atención con hiperactividad (TDAH), el trastorno obsesivo compulsivo (TOC), y dificultades de aprendizaje y del comportamiento. Presentamos el caso de un adolescente de 13 años diagnosticado con TT y con TDAH a los 6 y 10 años respectivamente. El paciente ha tenido una escolarización dificultosa y se encuentra con tratamiento médico de clozapina, aripiprazol, haloperidol y litio. Se aplica una batería neuropsicológica para evaluar la atención e inhibición, organización visuoespacial, memoria de trabajo, flexibilidad cognitiva, memoria verbal y memoria no-verbal, con el propósito de describir su perfil cognitivo de funciones ejecutivas y memoria. El estudio reveló que la atención está deteriorada pero que la inhibición se encuentra preservada; esto confirma el diagnóstico de TDAH y establece el subtipo de inatento para el caso en estudio. Las demás funciones ejecutivas evaluadas se encuentran severamente descendidas, situación que es coincidente con el perfil desarrollado por otros autores para el TT con comorbilidad TDAH. Sin embargo, no es claro si la disfuncionalidad ejecutiva se debe al TDAH que presenta, o a factores sociales y culturales derivados de las dificultades de escolarización causadas por el TT.

Tourette's disorder (TD) is a neurodevelopmental disorder that appears in early childhood characterized by the presence of phonic and motor tics that hinder socialization and the school learning process. TD has a varied comorbidity that includes attention deficit hyperactivity disorder (ADHD), obsessive compulsive disorder (OCD), learning and behavioral difficulties. We present the case of a 13-year-old adolescent diagnosed with TD and with ADHD at 6 and 10 years old respectively. The patient has had a difficult schooling and is under medical treatment of clozapine, aripiprazole, haloperidol and lithium. A neuropsychological battery is applied to evaluate the attention and inhibition, visuospatial organization, working memory, cognitive flexibility, verbal memory and non-verbal memory, with the purpose of describing its cognitive profile of executive functions and memory. The study revealed that the attention is impaired but that the inhibition is preserved; This confirms the diagnosis of ADHD and establishes the inattentive subtype for the case under study. The other executive functions evaluated are severely descended, a situation that coincides with the profile developed by other authors for TD with comorbid ADHD. However, it is not clear if the executive dysfunctionality is due to the ADHD it presents, or to social and cultural factors derived from the difficulties of schooling caused by the TD.

Toxic Myopathy due to Antidopaminergic Medication Without Neuroleptic Malignant Syndrome.

Severe recurrent proximal muscle weakness without neuroleptic malignant syndrome secondary to antidopaminergic medication has rarely been reported. We report a 29-year-old man with history of obsessive compulsive disorder and Tourette syndrome who presented with 2 months of worsening dyspnea 3 weeks after starting ziprasidone 40 mg daily that required mechanical ventilation. A year before, after an increased risperidone dose from 0.5 to 1 mg daily, he had developed proximal muscle weakness that spontaneously improved 2 months after discontinuation of risperidone. On this admission, his creatine kinase (CK) was 3318 units/L, and ziprasidone was discontinued. He fully recovered 2 months after discontinuation of ziprasidone, and his CK was 62 units/L. Genetic testing for limb-girdle muscular dystrophy was negative. This case highlights the importance of evaluating CK level in patients taking antidopaminergic medication with any suggestion of muscle weakness to prevent potentially life-threatening complication.

Effect of topiramate on sweat chloride level while screening for cystic fibrosis.

Cystic fibrosis is the most common life-limiting genetic condition in Caucasians caused by Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene mutations. Sweat chloride is the current gold standard for diagnosis where values >60 mmol/L are diagnostic and values >30 mmol/L are indeterminate. There is limited literature on the effect of medications on the sweat chloride values. We report a case of topiramate being responsible for false-positive testing which resulted in overutilisation of medical resources and psychosocial stress on the family. Topiramate should be considered during the interpretation of the gold standard testing as one of the cause of false-positive sweat tests.

Olfactory functioning in adults with Tourette syndrome.

Tourette syndrome is a chronic tic disorder characterized by motor and vocal tics. Comorbidities such as attention deficit hyperactivity disorder and obsessive compulsive disorder can be found. The overlap between neuroanatomical regions and neurotransmitter systems in the olfactory system and the pathophysiology of Tourette syndrome let us hypothesize altered olfactory performance in Tourette syndrome. The main objective of this study was to systematically assess olfactory functioning in subjects with Tourette syndrome and to compare it to healthy controls. We assessed 28 adults with Tourette syndrome (age 33.1±9.4 years, disease duration 23.7±9.7 years) and 28 healthy controls (age 32.9±9.0 years) matched in regard to age, sex, education and smoking habits. The "Sniffin Sticks" test battery was applied to assess odor threshold, discrimination, and identification. Additionally, the combined score of the odor threshold test, the odor discrimination test and the odor identification test of the "Sniffin Sticks" test battery was calculated. Although it was not the primary aim of this study, we assessed whether tics and comorbidity could contribute to olfactory alterations in adults with Tourette syndrome. Therefore, clinical scores were used to assess severity of tics and co-morbidity such as attention deficit hyperactivity disorder, obsessive compulsive disorder, anxiety and depression in subjects with Tourette syndrome. Pathology of the nasal cavities was excluded with rhinoendoscopy. Independent sample t-tests were applied to compare performance in olfactory tests. In the case of statistically significant differences (critical p-value: 0.05), multiple linear regression analysis was carried out to explore whether tic severity, social impairment, co-morbidity or medical treatment had an impact on the differences found. Descriptive values are reported as mean ± standard deviation. Tourette syndrome subjects showed lower combined scores (Tourette syndrome subjects 31.9 ± 5.1 versus healthy controls 35.0 ± 3.1; p = 0.007), odor identification scores (Tourette syndrome subjects 12.4 ± 2.0 versus healthy controls 13.7 ± 1.4; p = 0.008) and odor discrimination scores (Tourette syndrome subjects 12.1 ± 2.1 versus healthy controls 13.2 ± 1.6; p = 0.041) in comparison to healthy subjects, while there was no difference in odor threshold (Tourette syndrome subjects 7.3 ± 2.7 versus healthy controls 8.1 ± 2.2; p = 0.22). Seven out of 28 Tourette syndrome subjects (25%) scored in the range of the age- and sex-dependent combined score for hyposmia, while two of 28 healthy controls (7%) had a similar low combined score. None of the participants were found to have functional anosmia. Multiple linear regression analyses suggest that social impairment may a predictor for low combined score and odor identification score in Tourette syndrome subjects (p = 0.003). Compared to healthy controls, altered olfaction in adults with Tourette syndrome was found in this study. Normal odor threshold level but lower scores at tasks involving supra-threshold odor concentrations point towards a central-nervous alteration in the processing of olfactory information in Tourette syndrome.

Positive clinical effects of gamma knife capsulotomy in a patient with deep brain stimulation-refractory Tourette Syndrome and Obsessive Compulsive Disorder.

We report the first case of a patient with severe, intractable Tourette Syndrome with comorbid Obsessive Compulsive disorder, who recovered from both disorders with gamma-knife (GK) 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.

Streptococcal infection and immune response in children with Tourette's syndrome.

BACKGROUND: Streptococcal infection and basal ganglia inflammation are hypothesized to be involved in Tourette's syndrome (TS). There is a need for effective therapies for managing TS. We studied streptococcal infection and immunity in TS following immunomodulator (pidotimod) therapy. METHODS: Blood samples from 58 patients with TS and 128 age-matched healthy controls enabled measurement of antistreptolysin O (ASO), T cells, natural killer (NK) cells, interleukin-6 (IL-6) and interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α). Forty-four patients with abnormal T cell numbers were divided into two groups and treated with pidotimod granules (pidotimod group, n = 20) or pidotimod plus dopaminergic receptor antagonists (combination group, n = 24). Yale Global Tic Severity Scale (YGTSS) scores and immunologic indices were assessed after treatment. RESULTS: An ASO >1:200 was found in 22.4% of children with TS, 7.5% of controls, and 38.9% of children with both TS and attention deficit hyperactivity disorder (ADHD) compared to 15.0% of children with TS alone (P < 0.05). Children with TS showed decreased CD3(+) and CD4(+) T cells, CD4(+)/CD8(+) ratio, IL-6 and IL-8, increased NKC and TNF-α (P < 0.05) as compared to controls. ASO-positive children with TS had lower CD4(+) T cells as compared to ASO-negative children with TS, and lower IL-6 and IL-8 levels as compared to controls (P < 0.05). After 8 weeks of pidotimod treatment, IL-8 was increased compared to either tiapride hydrochloride or haloperidol and pidotimod (P < 0.05). CONCLUSIONS: Streptococcal infection in TS patients is associated with immune and cytokine dysfunction, which can be potentially managed with immunomodulator therapy.

Five-months-postoperative neuropsychological outcome from a pilot prospective randomized clinical trial of thalamic deep brain stimulation for Tourette syndrome.

OBJECTIVE: Tourette syndrome (TS) is a neuropsychiatric disorder presenting with motor and/or sonic tics associated with frontostriatal dysfunction. This study provided pilot data of the neuropsychological safety of bilateral thalamic deep brain stimulation (DBS) to treat medication-refractory TS in adults. METHOD: This study used a repeated-measures design with pretest and 3-month follow-up from start of continuous bilateral DBS. Five male patients underwent DBS surgery for medically refractory TS. Repeated-measures ANOVA was used to evaluate for any change in neuropsychological test scores, employing a false discovery rate. Outcome measures included 14 neuropsychological tests assessing psychomotor speed, attention, memory, language, visuoconstructional, and executive functions, as well as subjective mood ratings of depression and anxiety. RESULTS: Average age was 28.2 years (SD = 7.5) with 12-17 years of education. Participants were disabled by tics, with a tic frequency of 50-80 per minute before surgery. At baseline, subjects' cognitive function was generally average, although mild deficits in sequencing and verbal fluency were present, as were clinically mild obsessive-compulsive symptoms. At 3 months of continuous DBS (5 months after implantation), 3 of 5 participants had clinical reductions in motor and sonic tics. Cognitive scores generally remained stable, but declines of moderate to large effect size (Cohen's d > 0.6) in verbal fluency, visual immediate memory, and reaction time were observed. Fewer symptoms of depression and anxiety, as well as fewer obsessions and compulsions, were reported after 3 months of continuous high-frequency DBS. CONCLUSIONS: Bilateral centromedian-parafascicular thalamic DBS for medically refractory TS shows promise for treatment of medically refractory TS without marked neuropsychological morbidity. Symptoms of depression and anxiety improved.

The anteromedial GPi as a new target for deep brain stimulation in obsessive compulsive disorder.

Deep brain stimulation (DBS) is now well established in the treatment of intractable movement disorders. Over the past decade the clinical applications have expanded into the realm of psychosurgery, including depression and obsessive compulsive disorder (OCD). The optimal targets for electrode placement in psychosurgery remain unclear, with numerous anatomical targets reported for the treatment of OCD. We present four patients with Tourette's syndrome and prominent features of OCD who underwent DBS of the anteromedial globus pallidus internus (GPi) to treat their movement disorder. Their pre-operative and post-operative OCD symptoms were compared, and responded dramatically to surgery. On the basis of these results, we propose the anteromedial (limbic) GPi as a potential surgical target for the treatment of OCD, and furnish data supporting its further investigation as a DBS target for the treatment of psychiatric conditions.

Phenomenology and natural history of Tourette syndrome: brief summary or research / Fenomenologia e história natural da síndrome de Tourette: breve resumo da pesquisa

The phenomenology of Tourette syndrome is complex. Although overt motor and vocal tics are the defining features of Tourette syndrome, many individuals report experiencing sensory "urges," which are often difficult to describe. The natural history of this condition is also variable, with some individuals experiencing a marked reduction in tics by the end of the second decade of life while others go on to have a lifelong condition. The aim of this thesis was three-fold: (1) to develop a valid and reliable clinical rating instrument; (2) to investigate the sensory phenomena associated with Tourette syndrome; and (3) to document the course of tic severity over the course of the first two decades of life. Each of these three studies involved groups of patients with Tourette syndrome or a chronic tic disorder and each of these studies has been published in a peer-reviewed journal. The Yale Global Tic Severity Scale (YGTSS) has excellent psychometric properties that have been independently replicated. It has also emerged as the most widely used clinician-rated tic severity scale in randomized clinical trials around the world. Sensory phenomena, particularly premonitory urges, are commonly reported among individuals with Tourette syndrome by the age of 10 years. There is considerable overlap with the sensory phenomena described by individuals with Obsessive-Compulsive Disorder. Tics usually have their onset in the first decade of life. They then follow a waxing and waning course and a changing repertoire of tics. As documented in the third study, for a majority of patients the period of worst tic severity usually falls between the ages of 7 and 15 years of age, after which tic severity gradually declines. This falloff in tic symptoms is consistent with available epidemiological data that indicate a much lower prevalence of Tourette syndrome among adults than children. This decline in tic severity has been confirmed in subsequent studies...

A fenomenologia da síndrome de Tourette (ST) é complexa. Apesar de tiques motores e vocais serem as características definidoras da síndrome, muitas pessoas relatam ter urgências premonitórias (fenômenos sensoriais) de difícil descrição. A história natural da ST também é variável, com alguns indivíduos que experimentam uma redução acentuada nos tiques até o final da segunda década de vida, enquanto outros permanecem com sintomas ao longo de toda a vida adulta. Os objetivos principais desta tese são três: (1) desenvolver um instrumento de avaliação clínica com boa validade e confiabilidade para ST; (2) investigar os fenômenos sensoriais (FS) associados a ST; e (3) documentar o curso da gravidade dos tiques durante as duas primeiras décadas de vida. Para atingir esses objetivos incluíram-se grupos de pacientes clinicamente bem caracterizados e de artigos científicos publicados em periódicos internacionais de alto impacto. A Escala de Gravidade Global de tiques de Yale (YGTSS) apresentou excelentes propriedades psicométricas, o que foi replicado em estudos independentes. Também emergiu como a escala de gravidade mais utilizada em ensaios clínicos randomizados para ST em todo o mundo. Os FS, particularmente urgências premonitórias, são comumente relatados entre os indivíduos com ST com a partir da idade de 10 anos. Há uma sobreposição considerável com os FS descritos por indivíduos com Transtorno Obsessivo- Compulsivo (TOC). Os tiques costumam ter seu início na primeira década de vida e, então, seguem um curso flutuante com mudança do seu repertório. Conforme documentado no terceiro estudo, para a maioria dos pacientes, o período de pior gravidade dos tiques ocorre geralmente entre 7 e 15 anos de idade, após o qual a gravidade declina gradualmente. Esta queda dos sintomas de tiques é consistente com os dados epidemiológicos disponíveis que indicam uma prevalência muito menor de ST entre adultos do que crianças. Em resumo, há um esforço para incremento...

Type IIB thyroplasty for phonic tics in a pediatric patient with autism spectrum disorder: a case report.

OBJECTIVES/HYPOTHESIS: Autism spectrum disorders (ASDs) are commonly associated with Tourette syndrome (TS). TS is classically associated with tic production. A tic is defined as sudden, brief, involuntary production of movement (motor tics) or sound (phonic tics). STUDY DESIGN: Case report. METHODS: We present a case report of a 14-year-old boy with ASD and vocal tics. Vocal tic frequency was nearly 2000 per day and 90 dB in volume. He presented to our laryngology clinic after multiple failed attempts of pharmacologic management of vocal fold botulinum toxin injection. After evaluation in our clinic, we recommended a lateralization (type IIB) thyroplasty. An autologous cartilage graft from the superior thyroid ala was used and held in place with a bioresorbable mesh. Using 4-0 prolene sutures, the mesh was secured in place. The operation was well tolerated with minimal signs of aspiration, and he was discharged to his home within 48 hours. RESULTS: Six months postoperatively, there was 90% reduction in tic frequency and 50% reduction in intensity. Additionally, he has shown improved ability to converse with his peers, participate in school activities, and even has improved nutritional status. CONCLUSIONS: Alteration of laryngeal geometry could serve as an effective site of intervention for intractable phonic tics. Reduction of phonic tic frequency and intensity may also stimulate language development in patients ASD. We also demonstrate additional use of bioresorbable plates in pediatric laryngeal framework surgery. Additional neurophysiologic studies are needed to explore the mechanism by which midline lateralization thyroplasty influences phonic tic generation.

Surgical treatment of Tourette syndrome.

In severely affected, treatment resistant patients with Tourette syndrome (TS) new therapeutic strategies are urgently needed. Since 1999, 34 studies including more than 90 patients have been performed to investigate the efficacy and safety of deep brain stimulation (DBS) in the treatment of tics resulting in the vast majority of patients in an improvement of tics and in some patients even of comorbidities. Both surgery-related (e.g., bleeding, infection) and stimulation-related adverse events (e.g., loss of energy, blurred vision) seem to occur only in a minority of patients and not to cause significant impairment, respectively. Since randomized controlled studies including a larger number of patients are still lacking, up to now, no definite conclusion can be drawn. Therefore, at present time DBS is recommended only in adult, treatment resistant, and severely affected patients. However, most experts have no doubt that DBS is indeed effective in the treatment of tics. Future studies should aim to identify which target in which patient is optimal depending on the individual symptomatology.