0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Observation |

Bilateral Pallidal Stimulation for X-Linked Dystonia Parkinsonism FREE

Pettarusp M. Wadia, MD, DM, DNB; Shen-Yang Lim, MBBS, FRACP; Andres M. Lozano, MD, PhD; John R. Adams, MD, MSc, FRCPC; Yu-Yan Poon, RN; Cristina Torres Diaz, MD; Elena Moro, MD, PhD
[+] Author Affiliations

Author Affiliations: Movement Disorders Centre (Drs Wadia, Lim, and Moro and Ms Poon), and Division of Neurosurgery (Drs Lozano and Diaz), Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada; Centre for Movement Disorders, Markham, Ontario, Canada (Dr Adams); Jaslok Hospital and Research Centre, Mumbai, India (Dr Wadia); Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia (Dr Lim).


Arch Neurol. 2010;67(8):1012-1015. doi:10.1001/archneurol.2010.187.
Text Size: A A A
Published online

ABSTRACT

Objective  To report the clinical benefits of bilateral deep brain stimulation (DBS) of the globus pallidus internus (GPi) in a patient with X-linked dystonia parkinsonism (XDP).

Design  Case report.

Setting  Tertiary referral center.

Patient  A 40-year-old Filipino man with genetically confirmed XDP and severely disabling generalized dystonia.

Intervention  Bilateral GPi DBS.

Main Outcome Measures  The primary outcome measures were the Burke-Fahn-Marsden Dystonia Scale (BFMDS) severity and disability scores, and the secondary outcome measure was the Unified Parkinson Disease Rating Scores.

Results  At the 1-year postoperative follow-up, there was 80.4% improvement in the BFMDS severity score and 66.7% improvement in the BFMDS disability score.

Conclusion  Bilateral GPi DBS seems to be very effective in improving dystonia in XDP.

Figures in this Article

Lubag, or X-linked dystonia parkinsonism (XDP; DYT-3 [monogenetic form of dystonia]), is a rare genetic disorder that affects men and, rarely, women, with maternal roots from the Philippine island of Panay. The disorder most commonly presents in the third to fourth decade of life with progressive, severe dystonia dominating the first 10 to 15 years of illness; it is later replaced by parkinsonian features.1,2 Parkinsonism as a presenting feature is relatively uncommon. Those with onset of segmental dystonia usually progress to generalized dystonia within 5 or 6 years.1,2

The benefit of medical treatment for dystonia in XDP has not been consistent.1 To date, intracranial procedures have been attempted in 9 patients. Four patients who had unilateral thalamotomy, 2 who had unilateral pallidotomy, and 1 who had cerebellar implantation did not demonstrate clinical benefit.3,4 Two patients with XDP have had bilateral globus pallidus internus (GPi) deep brain stimulation (DBS). One had focal dystonia (jaw-opening dystonia) and slowly progressive disease,5 and the other had a rapidly progressive generalized dystonia with parkinsonism.6 Both patients' symptoms were markedly improved after bilateral GPi DBS. Here we report another case of XDP with severe, progressive generalized dystonia and moderate parkinsonism that has also responded favorably to bilateral GPi DBS.

REPORT OF A CASE

A 37-year-old Filipino man born on the Philippine island of Panay first presented with blepharospasm in 2005. The dystonia rapidly spread to involve the entire face and neck and affected his speech, with concurrent development of limb rigidity and bradykinesia (video 1, http://www.archneuro.com). During the subsequent year, the dystonia spread to involve his trunk and limbs, resulting in progressive gait dysfunction. Molecular genetic testing confirmed the clinical diagnosis of XDP by demonstrating a mutated allele (T) at DSC3 and a mutated allele (G) at DSC12 on the X chromosome. 7

The patient had been treated with botulinum toxin A injections for the orofacial and cervical dystonia (2 sessions of 400 IU each) with only partial relief, 12 mg/d of trihexyphenidyl, 75 mg/d of tetrabenazine, 15 mg/d of baclofen, 3.5 mg/d of clonazepam, 1 mg of lorazepam as required, and 100 mg/d of trazodone. Despite the above treatment he became severely disabled and was unable to care for himself, thus requiring admission to a nursing home. He was considered for DBS surgery for medically intractable dystonia.

When we first evaluated the patient in December 2007, he presented with severe generalized dystonia. His Burke-Fahn-Marsden Dystonia Scale (BFMDS) severity score was 67 (range, 0-120, with higher scores indicative of worse dystonia).8 Dystonia was present at rest in his limbs, face, neck, and trunk. He presented with frequent arching of the trunk (opisthotonus) and laryngeal stridor. He used a wheelchair, and a seatbelt was used to prevent him sliding from his chair. He required assistance for all basic activities of daily living. In addition to dystonia, he also presented with parkinsonian features (hypomimia, bradykinesia, and limb rigidity). His Unified Parkinson Disease Rating Scale (UPDRS) part III (motor) score was 40 of a possible 108. Neuropsychiatric assessment revealed mild executive dysfunction with impairment in visuospatial reasoning, sequencing, and working memory.9 Findings of brain and cervical spine magnetic resonance imaging (1.5 T) were normal.

The dystonia continued to progress until the time of surgery (preoperative BFMDS severity and disability scores were 13% and 4% worse, respectively, compared with 6 months earlier) (video 2; Table). The patient also developed swallowing difficulty, necessitating placement of a gastrostomy tube for feeding. At this time, 100 mg/d of trazodone had been added to his treatment regimen.

Table Graphic Jump LocationTable. Dystonia and Parkinsonism Scores Before and After GPi DBS Surgery at the 3-, 6-, and 12-Month Follow-ups

Bilateral GPi DBS was performed under general anesthesia in June 2008 using standard stereotactic and microelectrode techniques, as described previously.10 Briefly, a stereotactic frame (Leksell model G; Elekta Instrument, Atlanta, Georgia) was applied to the patient's head with local anesthetic; this was followed by magnetic resonance imaging (1.5-T magnet; General Electric, Milwaukee, Wisconsin). The anterior and posterior commissures were identified using axial T2-weighted images and 3-dimensional inversion recovery axial images. Images were transferred to a neuronavigation station and reformatted using the FrameLink 4.1 software (Mach 4.1 SNT StealthStation; Medtronic Inc, Minneapolis, Minnesota). Using StealthStation software, target coordinates for the most posteroventral part of the GPi were obtained. Microelectrode recordings were used to map the targets, starting 15 mm anterosuperior to the final targets, using 2 microelectrodes simultaneously advanced at steps of 0.5 mm. Microstimulation (1-second train of 0.2-millisecond pulses at 300 Hz and currents of 1-100 μA) was carried out at regular intervals. Intraoperative microrecordings were recorded and stored for analysis with Spike2 software (Cambridge Electronic Design, Cambridge, England).

Once the target was localized, bilateral DBS electrodes (3387; Medtronic Inc) were implanted at the sites, and a dual-channel implantable pulse generator (Kinetra; Medtronic) was placed in the right subclavicular region during the same surgical session. Postoperative brain magnetic resonance imaging confirmed the location of the electrodes in the GPi (Figure 1).11 Because of the severity of dystonia and inspiratory stridor, stimulation was started within a few hours of the operation. Stridor started to improve within 1 day of continuous stimulation, whereas phasic dystonic movements showed improvement a few days later. He continued to slowly improve with subsequent programming sessions during hospitalization (1 month).

Place holder to copy figure label and caption
Figure 1.

Postoperative coronal T2-weighted magnetic resonance image demonstrating the electrode locations in the posterolateral globus pallidum internus.

Graphic Jump Location

At the 3-month follow-up after surgery, the patient's generalized dystonia had improved remarkably (62% improvement in BFMDS severity score compared with before surgery) (video 3; Table; Figure 2 and Figure 3). He stopped taking baclofen. A swallowing assessment at that time showed mild improvement but not enough to start oral feeding. Soon after this follow-up, the Kinetra was accidentally switched off. The patient noticed worsening of his symptoms within a few hours, reaching his preoperative state 48 hours later, with recurrence of stridor and marked generalized dystonia (video 4 After switching back on the implantable pulse generator, improvement was seen within minutes, with further improvement occurring during the next 24 hours.

Place holder to copy figure label and caption
Figure 2.

Improvement in axial vs appendicular dystonia over time. Axial scores were calculated from a sum of the product of eye, mouth, neck, trunk, speech, and swallowing scores. Appendicular scores were calculated as a sum of bilateral upper and lower limb scores. BFMD stands for Burke-Fahn-Marsden Dystonia.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.

Change in dystonia scores over time for selected regions of the body using the Burke-Fahn-Marsden Dystonia (BFMD) severity scores.

Graphic Jump Location

At the 6-month postoperative follow-up, further improvement in the patient's dystonia was noted (Table), formal swallowing evaluation revealed significant improvement, and he was allowed to resume oral intake. Because there was further improvement in dystonia, treatment with tetrabenazine and trazodone was stopped.

At the 1-year follow-up (video 5; Table; Figure 2 and Figure 3), the BFMDS severity score had further improved by 80% compared with before surgery. Clonazepam use was reduced to 2 mg/d. The patient was able to swallow normally and eat solid food, and he no longer required the gastrostomy feeding tube. He was independent in all of his activities of daily living and able to cook his own meals and travel independently using public transportation. While there was no improvement in the UPDRS part III scores with GPi stimulation, there was a significant reduction in the part I and II scores (Table).

COMMENT

Surgical treatment with GPi DBS has been found to be effective for primary generalized and segmental dystonia in a class 1 clinical trial and in other large studies with blinded assessments.12,13 Genetic types of generalized dystonia such as DYT-1,12,13 DYT-11,14 and parkinsonism15 have been reported to markedly improve after GPi and subthalamic nucleus DBS surgery. Our case adds to the evidence supporting the use of bilateral GPi DBS in patients with severe XDP (DYT-3).

Of the patients in 2 previous reports of GPi DBS in XDP, 1 had a mild form of dystonia predominantly involving the oromandibular region and with relatively slow progression.5 The second patient with XDP with GPi DBS presented with a rapid progressive dystonia parkinsonism that started with blepharospasm (similar to our case). Both of the previous cases, though very different in phenotype, had good clinical response up to 1 year after GPi DBS.5,6

Unlike most primary genetic dystonias in which no pathology is demonstrated in postmortem studies,16 in XDP, neurodegenerative changes including neuronal loss and astrogliosis have been found in the caudate and putamen.3,4 Some studies have suggested that disinhibition of the nigral dopaminergic neurons owing to loss of striosomal GABAergic projection neurons would result in the hyperkinetic dystonia observed in XDP. At a later stage, dopamine-mediated toxic effects on striatal neurons would produce a subsequent striatonigral neurodegeneration, resulting in the dystonia being replaced by parkinsonism.17 Despite these clinicopathological differences to other genetic dystonias, a favorable response to GPi DBS sustained for 1 year in patients with XDP is encouraging. The efficacy of GPi DBS over ablative procedures may be related to a more complex mechanism of DBS in the stimulated structures.

Stimulation of the GPi in our patient was not only effective in improving appendicular, cervical, and truncal dystonia but was also effective in improving less frequent focal types of dystonia such as laryngeal stridor. Obstructed breathing and stridor due to laryngeal adductor dystonia has been described in XDP and can be severe enough to necessitate tracheostomy.18 The complete remission of stridor under GPi stimulation in our patient indicates that this may be a treatment option for this rare form of dystonia in cases in which other medical options have failed.

As has been reported earlier,19,20 the clinical improvement following bilateral GPi stimulation was gradual (Table). In our case there was rapid improvement in appendicular dystonia and a slower improvement in axial symptoms (Figure 2 and Figure 3).

As in the second case of XDP to undergo GPi DBS,6 the dystonia in our case rapidly worsened when the stimulator was accidentally turned off, further confirming the robust response to GPi DBS in XDP.

Contrary to previous articles,6 the UPDRS motor part did not show a benefit at the 1-year follow-up (Table). This is a remarkable observation and might support the investigation of another target in patients with XDP for whom parkinsonism is the most important symptom.

In conclusion, bilateral GPi DBS appears to be a safe and effective treatment option for patients with XDP with severe generalized dystonia and poor response to medication. This case report not only confirms the benefits of GPi DBS in XDP but also highlights the effectiveness of bilateral GPi DBS across different phenotypic presentations of dystonia in this disease (such as severe laryngeal dystonia). Long-term follow up is required to know if the benefits are sustained.

ARTICLE INFORMATION

Correspondence: Elena Moro, MD, PhD, Movement Disorders Centre, Toronto Western Hospital, 399 Bathurst St, McL7-402, Toronto, Ontario, Canada, M5T 2S8 (elena.moro@uhn.on.ca).

Accepted for Publication: November 2, 2009.

Author Contributions:Study concept and design: Wadia and Moro. Acquisition of data: Wadia, Lim, Lozano, Adams, Poon, Torres Diaz, and Moro. Analysis and interpretation of data: Wadia, Lim, Torres Diaz, and Moro. Drafting of the manuscript: Wadia, and Moro. Critical revision of the manuscript for important intellectual content: Wadia, Lim, Lozano, Adams, Poon, Torres Diaz, and Moro. Administrative, technical, and material support: Wadia, Lozano, Poon, Torres Diaz, and Moro. Study supervision: Lozano and Moro.

Financial Disclosure: Dr Moro reports having received honoraria from Medtronic for lecturing and consulting services. Dr Lozano reports receiving honoraria for consulting with Medtronic Inc.

REFERENCES

Evidente  VGAdvincula  JEsteban  R  et al.  Phenomenology of “Lubag” or X-linked dystonia-parkinsonism. Mov Disord 2002;17 (6) 1271- 1277
PubMed Link to Article
Lee  LVMunoz  ELTan  KTReyes  MT Sex linked recessive dystonia parkinsonism of Panay, Philippines (XDP). Mol Pathol 2001;54 (6) 362- 368
PubMed
Lee  LVMaranon  EDemaisip  C  et al.  The natural history of sex-linked recessive dystonia parkinsonism of Panay, Philippines (XDP). Parkinsonism Relat Disord 2002;9 (1) 29- 38
PubMed Link to Article
Waters  CHFaust  PLPowers  J  et al.  Neuropathology of lubag (x-linked dystonia parkinsonism). Mov Disord 1993;8 (3) 387- 390
PubMed Link to Article
Evidente  VGLyons  MKWheeler  M  et al.  First case of X-linked dystonia-parkinsonism (“Lubag”) to demonstrate a response to bilateral pallidal stimulation. Mov Disord 2007;22 (12) 1790- 1793
PubMed Link to Article
Martinez-Torres  ILimousin  PTisch  S  et al.  Early and marked benefit with GPi DBS for Lubag syndrome presenting with rapidly progressive life-threatening dystonia. Mov Disord 2009;24 (11) 1710- 1712
Link to Article
Nolte  DNiemann  SMuller  U Specific sequence changes in multiple transcript system DYT3 are associated with X-linked dystonia parkinsonism. Proc Natl Acad Sci U S A 2003;100 (18) 10347- 10352
PubMed Link to Article
Burke  REFahn  SMarsden  CDBressman  SBMoskowitz  CFriedman  J Validity and reliability of a rating scale for the primary torsion dystonias. Neurology 1985;35 (1) 73- 77
PubMed Link to Article
Saint-Cyr  JATrepanier  LL Neuropsychologic assessment of patients for movement disorder surgery. Mov Disord 2000;15 (5) 771- 783
PubMed Link to Article
Hutchison  WDLang  AEDostrovsky  JOLozano  AM Pallidal neuronal activity: implications for models of dystonia. Ann Neurol 2003;53 (4) 480- 488
PubMed Link to Article
Hamani  CMoro  EZadikoff  CPoon  YYLozano  AM Location of active contacts in patients with primary dystonia treated with globus pallidus deep brain stimulation. Neurosurgery 2008;62 (3) ((suppl 1)) 217- 225
PubMed Link to Article
Kupsch  ABenecke  RMuller  J  et al. Deep-Brain Stimulation for Dystonia Study Group, Pallidal deep-brain stimulation in primary generalized or segmental dystonia. N Engl J Med 2006;355 (19) 1978- 1990
PubMed Link to Article
Vidailhet  MVercueil  LHoueto  JL  et al. French SPIDY Study Group, Bilateral, pallidal, deep-brain stimulation in primary generalized dystonia: a prospective 3 year follow-up study. Lancet Neurol 2007;6 (3) 223- 229
PubMed Link to Article
Gil-Robles  SCif  LBiolsi  BTancu  CEl Fertit  HCoubes  P Neurosurgical treatment in childhood dystonias and dyskinesias [in Spanish]. Rev Neurol 2006;43 ((suppl 1)) S169- S172
PubMed
Moro  EVolkmann  JKonig  IR  et al.  Bilateral subthalamic stimulation in Parkin and PINK1 parkinsonism. Neurology 2008;70 (14) 1186- 1191
PubMed Link to Article
Kamm  C Early onset torsion dystonia (Oppenheim's dystonia). Orphanet J Rare Dis 2006;148
PubMed Link to Article
Goto  SLee  LVMunoz  EL  et al.  Functional anatomy of the basal ganglia in X-linked recessive dystonia-parkinsonism. Ann Neurol 2005;58 (1) 7- 17
PubMed Link to Article
Lew  MFShindo  MMoskowitz  CBWilhelmsen  KCFahn  SWaters  CH Adductor laryngeal breathing dystonia in a patient with lubag (X-linked dystonia-Parkinsonism syndrome). Mov Disord 1994;9 (3) 318- 320
PubMed Link to Article
Bittar  RGYianni  JWang  S  et al.  Deep brain stimulation for generalised dystonia and spasmodic torticollis. J Clin Neurosci 2005;12 (1) 12- 16
PubMed Link to Article
Yianni  JBain  PGGregory  RP  et al.  Post-operative progress of dystonia patients following globus pallidus internus deep brain stimulation. Eur J Neurol 2003;10 (3) 239- 247
PubMed Link to Article

Figures

Place holder to copy figure label and caption
Figure 1.

Postoperative coronal T2-weighted magnetic resonance image demonstrating the electrode locations in the posterolateral globus pallidum internus.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Improvement in axial vs appendicular dystonia over time. Axial scores were calculated from a sum of the product of eye, mouth, neck, trunk, speech, and swallowing scores. Appendicular scores were calculated as a sum of bilateral upper and lower limb scores. BFMD stands for Burke-Fahn-Marsden Dystonia.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.

Change in dystonia scores over time for selected regions of the body using the Burke-Fahn-Marsden Dystonia (BFMD) severity scores.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable. Dystonia and Parkinsonism Scores Before and After GPi DBS Surgery at the 3-, 6-, and 12-Month Follow-ups

References

Evidente  VGAdvincula  JEsteban  R  et al.  Phenomenology of “Lubag” or X-linked dystonia-parkinsonism. Mov Disord 2002;17 (6) 1271- 1277
PubMed Link to Article
Lee  LVMunoz  ELTan  KTReyes  MT Sex linked recessive dystonia parkinsonism of Panay, Philippines (XDP). Mol Pathol 2001;54 (6) 362- 368
PubMed
Lee  LVMaranon  EDemaisip  C  et al.  The natural history of sex-linked recessive dystonia parkinsonism of Panay, Philippines (XDP). Parkinsonism Relat Disord 2002;9 (1) 29- 38
PubMed Link to Article
Waters  CHFaust  PLPowers  J  et al.  Neuropathology of lubag (x-linked dystonia parkinsonism). Mov Disord 1993;8 (3) 387- 390
PubMed Link to Article
Evidente  VGLyons  MKWheeler  M  et al.  First case of X-linked dystonia-parkinsonism (“Lubag”) to demonstrate a response to bilateral pallidal stimulation. Mov Disord 2007;22 (12) 1790- 1793
PubMed Link to Article
Martinez-Torres  ILimousin  PTisch  S  et al.  Early and marked benefit with GPi DBS for Lubag syndrome presenting with rapidly progressive life-threatening dystonia. Mov Disord 2009;24 (11) 1710- 1712
Link to Article
Nolte  DNiemann  SMuller  U Specific sequence changes in multiple transcript system DYT3 are associated with X-linked dystonia parkinsonism. Proc Natl Acad Sci U S A 2003;100 (18) 10347- 10352
PubMed Link to Article
Burke  REFahn  SMarsden  CDBressman  SBMoskowitz  CFriedman  J Validity and reliability of a rating scale for the primary torsion dystonias. Neurology 1985;35 (1) 73- 77
PubMed Link to Article
Saint-Cyr  JATrepanier  LL Neuropsychologic assessment of patients for movement disorder surgery. Mov Disord 2000;15 (5) 771- 783
PubMed Link to Article
Hutchison  WDLang  AEDostrovsky  JOLozano  AM Pallidal neuronal activity: implications for models of dystonia. Ann Neurol 2003;53 (4) 480- 488
PubMed Link to Article
Hamani  CMoro  EZadikoff  CPoon  YYLozano  AM Location of active contacts in patients with primary dystonia treated with globus pallidus deep brain stimulation. Neurosurgery 2008;62 (3) ((suppl 1)) 217- 225
PubMed Link to Article
Kupsch  ABenecke  RMuller  J  et al. Deep-Brain Stimulation for Dystonia Study Group, Pallidal deep-brain stimulation in primary generalized or segmental dystonia. N Engl J Med 2006;355 (19) 1978- 1990
PubMed Link to Article
Vidailhet  MVercueil  LHoueto  JL  et al. French SPIDY Study Group, Bilateral, pallidal, deep-brain stimulation in primary generalized dystonia: a prospective 3 year follow-up study. Lancet Neurol 2007;6 (3) 223- 229
PubMed Link to Article
Gil-Robles  SCif  LBiolsi  BTancu  CEl Fertit  HCoubes  P Neurosurgical treatment in childhood dystonias and dyskinesias [in Spanish]. Rev Neurol 2006;43 ((suppl 1)) S169- S172
PubMed
Moro  EVolkmann  JKonig  IR  et al.  Bilateral subthalamic stimulation in Parkin and PINK1 parkinsonism. Neurology 2008;70 (14) 1186- 1191
PubMed Link to Article
Kamm  C Early onset torsion dystonia (Oppenheim's dystonia). Orphanet J Rare Dis 2006;148
PubMed Link to Article
Goto  SLee  LVMunoz  EL  et al.  Functional anatomy of the basal ganglia in X-linked recessive dystonia-parkinsonism. Ann Neurol 2005;58 (1) 7- 17
PubMed Link to Article
Lew  MFShindo  MMoskowitz  CBWilhelmsen  KCFahn  SWaters  CH Adductor laryngeal breathing dystonia in a patient with lubag (X-linked dystonia-Parkinsonism syndrome). Mov Disord 1994;9 (3) 318- 320
PubMed Link to Article
Bittar  RGYianni  JWang  S  et al.  Deep brain stimulation for generalised dystonia and spasmodic torticollis. J Clin Neurosci 2005;12 (1) 12- 16
PubMed Link to Article
Yianni  JBain  PGGregory  RP  et al.  Post-operative progress of dystonia patients following globus pallidus internus deep brain stimulation. Eur J Neurol 2003;10 (3) 239- 247
PubMed Link to Article

Correspondence

CME
Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Web of Science® Times Cited: 10

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles
X-linked Dystonia-Deafness syndrome. Mov Disord 1998;13(2):303-8.
[Genetics of dystonia]. Nervenarzt 2000;71(6):431-41.
JAMAevidence.com

The Rational Clinical Examination
Make the Diagnosis: Parkinsonism

The Rational Clinical Examination
Original Article: Does This Patient Have Parkinson Disease?