DBS Provides a New Lease on Life for Patients With Dystonia

Surgical interventions such as deep brain stimulation(DBS) are slowly becoming part of thestandard of care for patients with disabling dystoniawho are considered medically intractable. Theadvantages of DBS include adjustability and continuedaccess to the CNS target with minimal or no permanentdamage to important motor nuclei. Initial reportson the use of DBS in the treatment of generalizeddystonia have been very encouraging. The continueduse of this technique here and in Europe will establishDBS as a valuable interventional asset in the treatmentof various forms of dystonia, according to MicheleTagliati, MD, associate professor of neurology andchief of the Movement Disorders Center at the MountSinai Medical School in New York City.Some HMOs still consider the DBS procedure to beexperimental, even though the FDA has approved thistype of surgery. The HMO stance has generated somecontroversy, and a recent case involving Tagliati wasbrought to the attention of the television media.Tagliati, an internationally acclaimed expert in thefield of DBS, told Applied Neurology that the actualsurgery in the case had been approved, but the patient'sHMO denied payment for the implantation ofthe electrodes, which they considered "experimental."If nothing else, the incident showed lack of awarenesson the part of the HMO about what exactly DBSentails. An essential part of the total procedure requiresthat the electrodes be linked to a pacemakerthat must be specifically programmed for each patient.Tagliati explained that the neurosurgery without theimplantation and programming of the electrodes is, ofcourse, totally ineffective.Eventually, the HMO reviewed the case and allowedthe patient to have his electrodes reimplantedand reprogrammed. The results of the electrode reimplantationand reprogramming were highly successful,and the patient was able to regain a large degree ofmovement control and muscular coordination.In the Mount Sinai Movement Disorders Center, approximately50 patients with dystonia and 200 patientswith Parkinson disease (PD) and tremor currentlyare treated using DBS, according to Tagliati.During the late 1980s, the DBS procedure was developedfor patients with essential tremor, and it also wasfound to be particularly effective in controlling casesof intractable tremor in PD. In the early 1990s, advancesin neuroscience research increased the understandingof the mechanisms involved in PD and haveled to the routine use of DBS, which can actually beconsidered a second therapeutic revolution in thetreatment of PD following the discovery of levodopa.In the late 1990s, therapy was focused on the DBS ofthe subthalamic nucleus and the globus pallidus parsinterna (GPi). DBS became a treatment modality forpatients who had become refractory to levodopa andother drugs. Even after DBS, many patients still requiredat least a 50% dosage of their usual medication,but there was a 50% better outcome in those patientswho had received this form of combination therapy.Tagliati pointed out that at Mount Sinai, 2 days areregularly scheduled for the surgery. Tagliati's colleagueRon Alterman, MD, associate professor of neurosurgery,performs most of the DBS procedures. About 2patients a week undergo the procedure, said Tagliati.OVERVIEW OF DYSTONIADystonia is a neurologic syndrome consisting of involuntary,patterned, sustained, and often repetitivemuscle contractions of opposing muscle groups. Theseagonistic-antagonistic muscle contractions often inducetwisting of the body, spasmodic movements, orabnormal postures. Dystonia presents itself in a richvariety of ways and possesses a highly variablecourse. Because of this varied expression, it is oftenmisdiagnosed or not recognized.1Underreporting has produced some confusion regardingthe prevalence of dystonia, but more than300,000 cases in the United States is a reasonable estimate,putting the number of cases at about the samelevel as that of multiple sclerosis. The dystonic disordersare generally classified according to 3 criteria: (1)age at onset (ie, adult vs child), (2) region of the bodyinvolved (ie, focal or generalized), and (3) cause (ie,primary or secondary). As in PD, the dystonic disordersare usually divided into primary and secondary,depending on their etiology.2,3Primary dystonia. Included in a diagnosis of primarydystonia are syndromes in which this disorder is thesole observable clinical manifestation (other thantremor) and no pathology is apparent. Primary dystoniacan be inherited, and a number of involved geneshave already been identified. Within this group of disordersis idiopathic torsion dystonia, a childhood conditionoriginally known as Oppenheimer dystonia.However, the most common form of primary dystoniais sporadic adult-onset focal dystonia.2Secondary dystonia. This is a varied group of disorderslargely induced by drugs and environmental toxins.Dopamine receptor inhibitors classically have beenassociated with dystonic complications (tardive dystonia).Other brain lesions associated with dystonia includecerebral palsy (athetoid form), brain trauma, cerebralhypoxia, infectious disease, postinfectious states,and exposure to certain chemical entities includingmanganese, cyanide, and 3-nitropropionic acid.2A prime clinical feature of dystonia, which differentiatesit from the other hyperkinetic movement disorders,is repetitive and patterned muscular contractionsat the same site. This is in contrast with the clinical featuresof Huntington disease, in which brief movementsoccur continuously and flow randomly from one partof the body to another.1 The coexistence of tremor oftencomplicates the diagnosis of dystonia. Dystonic tremoris differentiated from essential tremor by recognizablepatterns of activation and directionality.1Available treatments for dystonia include emotionaland physical support, neurorehabilitation, physicaltherapy, pharmacologic interventions, and surgery.Pharmacologic therapy includes anticholinergics, benzodiazepines,baclofen, dopaminergic agents, and botulinumtoxin.2 Aside from botulinum toxin, the use ofwhich is limited to focal dystonias, pharmacologictherapies have not been particularly effective andhave been associated with adverse effects.NEUROSURGICAL INTERVENTIONSSurgical treatment for movement disorders can betraced back to the 1930s with what Tagliati referred toas "stone age" procedures, such as resection of the primarymotor cortex, extirpation of the caudate nucleus,and resection of the globus pallidus and ansa lenticularis.During the 1950s, modern procedures includingthalamotomy and pallidotomy were developed. Withthe discovery of levodopa therapy in the 1960s and1970s, the focus of treatment shifted away fromsurgery, in part because many neurologists had becomedisappointed with surgical outcomes.3Because of disappointing results with surgical interventions--including high morbidity and mortality--older neurologists still continue to see neurosurgeryin a somewhat suspicious light. A popularfear of neurosurgery at that time was exemplified bythe Tennessee Williams' play Suddenly, Last Summer(1959), in which a frontal lobotomy was to be used asa sinister weapon to destroy the unsavory and scandalousmemories of the play's heroine.4The work of Tagliati and others are leading to greatchanges in medicine and great hope for patients.Much of the early DBS research work and hands-ontraining were done in Switzerland and France, particularlyunder the direction of Alim-Louis Benabid, MD,PhD, chief of neurosurgery at the University of Grenoblewho is regarded by many as the "Father of DBS."NEW LEASE ON LIFEDBS has been remarkably successful in the treatmentof dystonia, particularly generalized dystonia, inTagliati's experience. Indeed, such treatment hasgreatly improved the quality of life of affected children.Drug therapy often is not successful and also canaffect a child's cognitive abilities. DBS has become apromising procedure for these young persons. Indeed,many children with genetically based dystonia (the DYT1 defect on chromosome 9) have responded wellto DBS, said Tagliati, and should be considered primecandidates for the procedure.Other patients who have responded well to DBS, inTagliati's experience, are those with primary dystonia,whereas a less than optimal response is more oftenseen in patients with secondary dystonia. Therefore,when patients are candidates for DBS, it is very importantto distinguish between primary and secondarydystonia, he said.When patients are well-selected, well-implanted,and well-programmed, the results following DBS canbe astonishingly good. On average, 50% to 60% ormore of patients treated with DBS have shown excellentresponses, said Tagliati. "Our center at MountSinai reflects the same results as many others that performDBS. Results in primary dystonia studies havedemonstrated an average improvement rate of 75%.These are diseases in which there was little help to offer5 or 10 years ago--until the development of DBS,"said Tagliati.Failures reported from several centers basicallywere caused by 3 factors: poor candidate selection,misplacement of electrodes, and the improper programmingof electrodes (accounting for 35% of failures).Tagliati was emphatic in clarifying why DBSfailures sometimes occur: "The actual neurosurgery isnot just a quick fix. The correct combination of settingsin the implanted device that governs voltage and electricalpulse rate are essential for success. These parametersvary with each individual patient."In treating dystonia with DBS, the clinician maywait weeks or even months to see improvement. Inmost cases, if the DBS procedure is done well and coordinatedclosely with the treatment team, the outcomesof dystonic patients can be quite satisfying.Three areas are usually targeted for DBS, all ofwhich are in the basal ganglia. Tagliati specified that"for tremor we target the nucleus ventralis intermediusof the thalamus, the anatomic center intimatelyinvolved in involuntary shaking and tremor. ForParkinson disease, there are 2 targets: the subthalamicnucleus and the globus pallidus pars interna. Currentthinking based on encouraging data favors the subthalamicnucleus as the target for DBS." However,both targets in PD have produced impressive resultsusing DBS. In dystonia, targeting the GPi has producedthe best results, and this target has become reasonablywell established, said Tagliati. "We are stillvery empirical at this stage in our knowledge, and werely on a lot of trial and error in our work, mainly becauseour understanding of the underlying mechanismsremains limited," Tagliati added.TREATMENT CENTERS GROWINGDuring the mid-1990s, DBS was considered an experimentalprocedure, but now there are many centersacross the country that are achieving excellent results.Many large medical facilities, especially academic centers,have vigorous DBS programs in place. Academiccenters, above all, can provide the expert team effortthat is essential for successful outcomes. The team includesa neurologist to select appropriate patients, aneuropsychiatrist to exclude those with dementia (animportant exclusion criterion), a neurosurgeon withextensive experience in performing the stereotacticelectrode placement procedure, and a programmerwho can individualize voltage levels and frequencieswith a high degree of accuracy.Because of the intensely coordinated effort involvedin DBS, follow-up by the original team is veryimportant for optimal outcomes. A way to overcomepossible "overload" at the implantation center mightbe to have a primary medical facility with severalsatellites centers, each with neurologists who refer patientsfor the implantation procedure, Tagliati suggested.These referring neurologists would then have easyaccess to all patient medical records and images on acomputer network for in-depth follow-up care whenpatients return for evaluation to their community officesor hospitals.TRAINING IN DBSTraining in the DBS procedure is ongoing, and it isroughly divided into 2 efforts. Training is being spearheadedby the device industry and is making DBS informationavailable to neurologists across the country.Medtronics, Inc, the manufacturer of the implanteddevice, is particularly active--providing focus groupsand hands-on workshops in major medical centers,explained Tagliati. The American Academy of Neurologyis also involved in training; they organize coursesthat attract a great deal of interest nationwide. ?REFERENCES1. Jankovic J, Fahn S. Dystonic disorders. In: Jankovic J, Tolosa E, eds. Parkinson'sDisease and Movement Disorders. 2nd ed. Baltimore: Williams & Wilkins.1993:337-374.
2. DeLong MR, Luncos JL. Parkinson's disease and other movement disorders.In: Kasper DL, Fauci AS, Longo DL, et al, eds. Harrison's Principles of InternalMedicine. Vol 2. 16th ed. New York: McGraw-Hill. 2005:2406-2418.
3. Walter BL, Vitek JL. Surgical treatment for Parkinson's disease. Lancet Neurol.2004;3:719-728.
4. Dirks T. A review of Suddenly, Last Summer (1959). Available at: www.filmsite.org/suddl.html. Accessed May 21, 2006.