Christian Saleh

Bilateral Globus Pallidus Stimulation in Westphal Variant of Huntington Disease

Huntington’s disease (HD) is a neurodegenerative disorder presenting with progressive motor, cognitive, and behavioral symptoms. The genetic aspects of HD are well characterized and are consistent with abnormal expansion of a cytosine-adenine-guanine (CAG) trinucleotide sequence in the huntingtin (HTT) gene located on chromosome 4. Mutant HTT induces neuronal death in selected areas of the brain, among which the neostriatum represents the main target (1). The Westphal variant of HD (W-HD) accounts for 8–10% of all cases of HD and is characterized clinically by predominance of dystonia, myoclonus, rigidity, motor slowing, and unsteady gait over hyperkinetic (choreic) manifestations (2).The pathophysiologic basis of these clinical manifestations apparently resides on a pronounced degeneration of the direct monosynaptic inhibitory striato-pallidal projection (the so-called “direct” pathway), which ultimately results in increased inhibition of the ventrolateral thalamus (2,3). Patients with this rare form often present with seizures, cerebellar ataxia, action tremor, and oculomotor abnormalities and show more widespread brain atrophy (3). Progressive cognitive impairment also is found, with involvement of planning, attention, cognitive flexibility, abstract thinking, initiating appropriate actions, and inhibiting inappropriate actions. Memory also is affected as the disease progresses. Cognitive deterioration worsens over time, ultimately leading to overt subcortical dementia (3). Neuropsychiatric manifestations also are present and include anxiety, depression, compulsive behavior, irritability, aggression, anorexia, drug addiction, social withdrawal, and a reduced display of emotions (3). An expansion of more than 60 CAG repeats in the HTT gene, which represents about 4% of the whole spectrum of mutations, is usually found in patients with W-HD. The juvenile onset (J-HD), that is, before age 20, and the paternal inheritance are hallmarks of W-HD (4). Drug therapy, which shows some limited efficacy on hyperkinetic symptoms of classical HD, has little if any effect in W-HD. Neuromodulation of deep brain structures is a procedure widely used in the treatment of movement disorders such as idiopathic Parkinson disease, essential tremor and generalized dystonia (5–11). Its use in HD is limited to very few cases with some documented improvement on hyperkinetic symptoms in patients with classical HD (12–21). A,single case of surgical lesioning (bilateral pallidotomy) for treatment of the W-HD has been reported so far but clinical outcome was ineffective, especially on axial symptoms (22). No data exist to our knowledge on deep brain stimulation (DBS) in W-HD.

Temporary deep brain stimulation in Gilles de la Tourette syndrome: A feasible approach?

Background: Gilles de la Tourette Syndrome (GTS) is a complex neuropsychiatric disorder, characterized by chronic motor and vocal tics, associated in 50–90% of cases with psychiatric comorbidities. Patients with moderate and severe clinical picture are treated with psychotherapy and pharmacological therapy. Deep brain stimulation (DBS) is reserved for pharmacological refractory GTS patients. As GTS tends to improve with time and potentially resolves in the second decade of life, the major concern of DBS in GTS is the age at which the patient undergoes surgical procedure. Some authors suggest performing DBS after 18 years, others after 25 years of age. Case Description: We present a 25-year-old patient with GTS, who was aged 17 years and was treated with thalamic DBS. DBS resulted in progressive and sustained improvement of tics and co-morbidities. After 6 years of DBS treatment, it was noted that the clinical improvement was maintained also in OFF stimulation setting, so it was decided to keep it off. After 2 years in off-setting and stable clinical picture the entire DBS device was removed. Six months after DBS device removal the patient remained symptom-free. Conclusions: DBS is a therapeutic option reserved for severe and refractory GTS cases. In our opinion DBS might be considered as a temporary application in GTS.

Why so many deep brain stimulation targets in Tourette’s syndrome? Toward a broadening of the definition of the syndrome

Tourette’s syndrome (TS) is a neuro-developmental disorder characterized by simple or complex motor and sound tics starting before age 18 and that last for more than 1 year (TSA definition). TS can be considered as a sensory-sensitive-motor circuit dysfunction along with a strong behavioural component (Zapparoli et al. 2015a, b). It typically affects males more frequently than females (Khalifa and von Knorring 2003). The prevalence of tic disorder is about 0.85–1 % in the adults and up to 20 % in children according to (Robertson 2015). In the whole spectrum 90 % of patients present with at least one comorbidity, such as obsessive–compulsive disorder (OCD), learning difficulty, poor impulse control, self-injury behaviour (SIB), attention-deficit-hyperactive-disorder (ADHD), non-obscene socially inappropriate behaviour (NOSI) and autistic spectrum disorder (Eapen et al. 2015; Robertson et al. 2015). Coexisting diseases are depression and anxiety symptoms (Robertson 2015). Tics are the main components in childhood, whereas OCD and other psychopathological traits are encountered more frequently in adolescence. TS is considered increasingly a neurological disorder rather than a psychiatric disease. Traditionally TS is differentiated in pure-Tourette syndrome and Tourette syndrome-plus (Eapen et al. 2015). More recently five phenotypes have been identified by the London TS group. Phenotypes are (1) minimally affected class, (2) CMT (chronic motor tics) ? OCD, (3) TS ? OCD/OCB, (4) TS ? OCD, (5) TS ? OCD ? ADHD (Grados and Mathews 2008; Eapen and Robertson 2015; Eapen et al. 2015). Based on our large experience OCD is probably the most debilitating and disturbing aspect of the disease, foremost from a social impairment standpoint (Servello et al. 2015), followed by sound tics and motor tics. Over the last decades, deep brain stimulation (DBS) has been considered an effective treatment option in severe TS patients’ refractory to medication and by psychotherapeutic or cognitive behavioural therapies.

How to Avoid Twiddler's Syndrome in Deep Brain Stimulation for Dystonia?

To the Editor: We report an unusual hardware complication after deep brain stimulation (DBS) for primary dystonia. A 43-year-old woman with primary refractory dystonia, characterized by dysphonia, dysphagia, and torticollis, underwent DBS of the posteroventral globus pallidus internus. Three days later, the patient had a second surgical procedure for lead internalization with the positioning of the internal pulse generators (IPG, Kinetra-Medtronic, Minneapolis, MN, USA) placed subcutaneously in the right subclavicular region. Both procedures were uneventful. Postoperative T1-weighted magnetic resonance imaging showed electrodes in place (Fig. 1). One week after the second procedure, the IPG was switched on, resulting in a slow and progressive improvement of dystonia. However, after six months, the patient experienced worsening of dysphonia with dysarthria. IPG interrogation evidenced high levels of impedance (>2000 ;W) indicating potential hardware malfunction. The patient was hospitalized and plain x-rays of the skull, neck, and chest were performed, showing twisting of the two lead cords with a doublehelix pattern (Figs. 2 and 3). The patient had manipulated the IPG, causing a rotation of the IPG in the subcutaneous pocket that resulted in a twisting of the extension wires. This rare complication is known in the scientific literature as Twiddler’s syndrome. The first description of this phenomenon dates back to 1968 (1). Bayliss and colleagues from Canada called Twiddler’s syndrome the rotation of the cardiac pacemaker within its subcutaneous pocket secondary to external manipulation (1). However, contrary to the cardiac literature, only recent DBS studies reported this complication (2–6). In our patient, we suspect equally that repetitive external manipulation of the IPG may have caused displacement and rotation of the pulse generator. Initially, we thought that anchoring the IPG to the muscular fascia might be a fast and simple solution for this kind of complication. However, a review of the literature showed that displacement of devices occurs even if the IPG is sutured to the muscular fascia (2,4,5). Anchoring is consequently not sufficient to avoid device displacement. We propose therefore to position the IPG in a submuscular pocket. In this way, the IPG is less likely object to manipulation by external factors. The lead internalization is performed under general anesthesia. Leads are exposed in the retromastoid region. A horizontal linear subclavicular skin incision is performed, and subsequently, the muscular fascia coagulated and opened in a linear fashion. The muscle fibers are dissected with a smooth technique to the ribs. A submuscular pouch is obtained. The extension wires (60 cm) are internalized subcutaneously from the retromastoid region to the subclavicular region. The extension wires are connected proximally to the lead and distally to the IPG. The IPG is positioned in the pocket and fixed to the profound fascia. Advantages of submuscular positioning are better aesthetic results, a more stable placed IPG, and better protection from external trauma. The disadvantages of submuscular IPG placement consist of a more invasive procedure and consequently also in a more difficult substitution of a submuscular-placed IPG.

Deep brain stimulation for Parkinson's disease prior to L-dopa treatment: A case report.

Background: Leva-dopa (L-dopa) is the gold-standard treatment for Parkinsons disease (PD). Deep brain stimulation is generally reserved for patients who become refractory to l-dopa treatment. Case Description: We present a male patient with a 9-year course of PD who at 53 years of age preferred deep brain stimulation (DBS) of the subthalamic nucleus over initial l-dopa treatment. The patient argued that he wanted to avoid the serious adverse effects of l-dopa, which would have presented within his time of full professional activity. DBS resulted in significant motor improvement lasting for 6 years without l-dopa treatment. Conclusion: Large multicentre-based international trials with long follow-ups are needed to answer the effectiveness of early DBS in PD.

The pros and cons of intraoperative CT scan in evaluation of deep brain stimulation lead implantation: A retrospective study

Background: Deep brain stimulation (DBS) is an established therapy for movement disorders, such as Parkinsons disease (PD), dystonia, and tremor. The efficacy of DBS depends on the correct lead positioning. The commonly adopted postoperative radiological evaluation is performed with computed tomography (CT) scan and/or magnetic resonance imaging (MRI). Methods: We conducted a retrospective study on 202 patients who underwent DBS from January 2009 to October 2013. DBS indications were PD, progressive supranuclear palsy, tremor, dystonia, Tourette syndrome, obsessive compulsive disorder, depression, and Huntingtons disease. Preoperatively, all patients underwent brain MRI and brain CT scan with the stereotactic frame positioned. The lead location was confirmed intraoperatively with CT. The CT images were subsequently transferred to the Stealth Station Medtronic and merged with the preoperative planning. On the first or second day after, implantation we performed a brain MRI to confirm the correct position of the lead. Results: In 14 patients, leads were in suboptimal position after intraoperative CT scan positioning. The cases with alteration in the Z-axis were corrected immediately under fluoroscopic guidance. In all the 14 patients, an immediate repositioning was done. Conclusions: Based on our data, intraoperative CT scan is fast, safe, and a useful tool in the evaluation of the position of the implanted lead. It also reduces the patients discomfort derived from the transfer of the patient from the operating room to the radiological department. However, intraoperative CT should not be considered as a substitute for postoperative MRI.

How to compare clinical results of different neurosurgical centers? Is a classification of complications in neurosurgery necessary for this purpose?

A classification of complications in neurosurgery, to be approved and validated by the scientific community, has been advocated as the main vehicle for comparing different series of patients having undergone surgery in different centers and/or at different times.[12] The ultimate goal of such a classification would be-in the long period and from the point of view of healthcare policy-the quality improvement of health services to be offered to patients. Such improvement (which would also be relevant with regard to saving economic resources) could be achieved through an analysis-with quantitative (or at least objective) data-to establish which medical center guarantees the best clinical results in a specific surgical procedure. If a simple, practical-and therefore applicable in any medical center-classification of complications could achieve this purpose, it would be logical that all efforts should be made toward developing it. Should this aim not be pursued, or should it be achieved through different tools, the effort of defining a complications’ classification would be a mere intellectual exercise lacking any practical usefulness. Historical overview: The refinement of the definition of surgical complications and of classification of complications in general surgery The question of how to define negative results following invasive therapeutic procedures has been a matter for discussion for many years now in the field of general surgery. A classification of complications to be accepted by the entire scientific community has not been developed yet, even starting from the definition itself of complication; any proposed definition of complication,[4,5,6,16,17] as a matter of fact, has not been approved by those authors who later dealt with this subject. Sokol and Wilson,[17] for example, define as a complication “any undesirable, unintended, and direct result of an operation affecting the patient, which would not have occurred had the operation gone as well as could reasonably be hoped;” the authors themselves admit, however, that establishing in each case if a negative event could or could not be considered as a complication entails wide margins of subjectivity. The attempt to precise a classification of complications faces even harder obstacles, in as much the clarification of categories within which to classify the innumerable unexpected events that might occur in the surgical field will necessarily be either too generic or too specific. In the former case, such classification will include many different negative events not strictly homogeneous with regard to the cause of the complication; in the latter one, such classification will appear fastidious and not handy because of the excessive number of categories to be detailed. The most thorough paper in this field-dealing with cholecystectomies-was published by Clavien in 1992.[4] In this paper, a fundamental concept is introduced, that is, the grading of complications based on patients’ morbidity on the basis of the severity of any residual or lasting disability. Other authors also[8,9] stated that life quality measures should be used to evaluate surgery outcomes. Clavien,[4] moreover, recommended considering as “complications” only unexpected negative events; any predictable unfavorable outcome caused by a specific surgical risk inherent to the procedure being on the contrary a “sequela.” This idea, also approved by other authors,[2,16,10] logically introduces the concept of a definition of surgical risk (i.e., the likelihood that a patient might develop a disability following a technically irreproachable surgical procedure). In the field of general surgery, Dindo et al., in 2004,[5] specified the complexity of surgery in three main categories as follows. Type A: surgical procedures without opening of the abdominal cavity; type B: abdominal procedures except liver surgery, representing instead type C procedures. Complications have been classified in five grades according to the importance of the therapy necessary to treat them. Grade I complications, requiring only routine drugs, include transient atrial fibrillation, atelectasis, transient elevation of serum creatinine; grade II complications, requiring specific drug treatment, include tachyarrhythmia, pneumonia, urinary tract infection; grade III complications, treated with invasive procedures, include bradyarrhythmia requiring pacemaker implantation, bronchopleural fistula, and stenosis of the ureter treated surgically. Grade IV includes single or multiorgan dysfunction and life threatening complications requiring intensive care unit management. Grade V represents the death of the patient. For each of the three classes of risk in which complications have been grouped, every type of negative event occurred much more frequently in group C patients (P < 0.0001).

Management of patent foramen ovale in patients with cryptogenic stroke: Is device closure superior to medical treatment? A brief review

Background: Recent randomized controlled trial (RCTs) comparing percutaneous closure with antithrombotic treatment in patients with patent foramen ovale (PFO) and cryptogenic stroke revealed inconsistent results. Indeed, there is still no consensus on the management of these patients, namely closure or medical therapy treatment. Methods: To take stock of the PFO management after cryptogenic stroke, we conducted a literature review that included 16 articles dealing with different therapeutic strategies and long-term outcomes of these results. Results: The reviewed studies showed great methodological diversity rendering an exhaustive and balanced comparison between studies difficult. Low recurrence rates under prevention regimens, crossovers, procedure- and device-related complications, as well as inappropriate patient selection might explain the inconsistency of trials. However, despite the methodological heterogeneity certain patterns could be detected. It appears that device closure as secondary prevention measure is an effective and safe procedure reducing the recurrence of neurological events in cryptogenic stroke patients <60 years with large PFOs. Standardization of procedures and larger trials are needed to arrive to definitive conclusions. Conclusion: In cryptogenic stroke patients <60 years with large PFOs, PFO closure seems to be safe and more effective compared to medical treatment alone. For all other patients group, for example, patients >60 years further trials are needed to clarify the role of PFO closure.

Dual floor burr hole technique in deep brain stimulation: A retrospective study on 209 patients

Background: Skin erosion/infections due to deep brain stimulation hardware are highly worrisome complications. They can lead to the removal of the entire deep brain stimulation device, and consequently hold the whole treatment in otherwise pharmacologically refractory patients. Several techniques have been used such as C-shape skin incision and dual floor burr hole or single passage of connecting cables to reduce the incidence of skin complications. Methods: In this paper, we describe our experience in 209 patients using a dual-floor burr hole technique to reduce skin adverse effects. Conclusion: The dual floor burr hole technique is a safe technique with a low incidence of skin erosions and complications.

Creativity Assessment in Subjects with Tourette Syndrome vs. Patients with Parkinson’s Disease: A Preliminary Study

(1) Background: Literature suggests that high levels of dopamine are associated with creative thoughts. Tourette Syndrome (TS) patients have high dopamine levels, while Parkinson’s Disease (PD) subjects have low dopamine levels. Consequently, TS individuals are supposed to have a major and PD patients less creative output. Moreover, dopamine medications may alter the level of creativity, and therefore Quality of Life, in both pathologies. (2) Methods: The aim of the study was to verify the hypothesis of TS patients having higher creative scores than PD patients. The assessment consisted of the administration of the Creative Thinking ASK Test. There were 54 participants—36 males and 18 females—i.e., 27 TS patients and 27 PD subjects. Age of the sample was 35 to 57 years old, high school certificate was required. (3) Results: TS sample (103.11 ASK average score) was more creative than PD sample (94.11 ASK average score). (4) Conclusions: The results supported the aforementioned hypothesis: TS sample resulted in having higher creative scores than PD sample. Dopamine and other neurotransmitters of TS and PS appear to affect subject’s creativity. Further studies with creative assessments in TS and PD patients are needed to support the preliminary results of our study.