Brief Report

Life-Threatening Dystonia–Dyskinesias in a Child: SuccessfulTreatment With Bilateral Pallidal Stimulation

*Lucia Angelini, MD, *Nardo Nardocci, MD, *Margherita Estienne, MD, *Chiara Conti, MD,†Ivano Dones, MD, and †Giovanni Broggi, MD

Departments of *Neuropediatrics and †Neurosurgery, National Neurological Institute “C. Besta,” Milan, Italy

Summary: We report a 13-year-old boy who developed se-vere, refractory dystonia–dyskinesias as an abrupt worsening ofa previously nonprogressive movement disorder. The move-ments became continuous, requiring artificial respiration andcontinuous sedation in the intensive-care unit. Various drugsand drug combinations failed to achieve control. The child was

then treated successfully with bilateral pallidal (GPi) stimula-tion as shown in the videotape. Four months later and withoutmedication, the boy regained autonomous gait and audiblespeech; his neurologic condition continues to improve.KeyWords: Deep brain stimulation—Pallidal stimulation—Refractory dystonia—Refractory dyskinesia.

Life-threatening dystonia is rare in children. In suchcases, the dystonic spasms may be so severe that theycompromise respiration, cause hyperthermia and evenmuscle necrosis; successful control is difficult toachieve.1,2 We present the case of a child in whom anearly-onset, nonprogressive symptomatic dystoniasuddenly worsened to an intractable dystonic–dyskinetic condition. Various drugs did not relieve thespasms and movements, but control was eventuallyachieved, as shown in the videotape, by deep brainstimulation.

CASE REPORT

This 13-year-old boy, the only son of healthy, non-consanguineous parents, was born at term after a normalpregnancy and delivery. Apgar scores were 8 and 10 at 1and 5 minutes, respectively. Psychomotor developmentwas normal until 5 months of age when he developed a

fever and severe irritability 1 week after an anti-poliovaccination followed by loss of developmental mile-stones. At 8 months of age neurologic evaluation re-vealed bilateral dystonic postures associated with pyra-midal signs in the lower limbs; a diagnosis of cerebralpalsy was posed. Prominent dystonia was confirmedat subsequent examinations, and at 3 years of age se-vere dysarthria and mild cognitive impairment weredocumented.

Autonomous gait was eventually achieved at 5 yearsof age. The neurologic picture remained unchanged untilMarch 1998 when, at age 12, he developed paroxysmsof segmental or generalized, rapid, high-amplitude in-voluntary movements, which appeared sporadicallyand lasted a few minutes to an hour. The frequency ofthe attacks increased progressively until, in January1999, they became continuous. Levodopa at a dosage ofup to 500 mg per day, up to 4.5 mg haloperidol per day,and up to 100 mg clotiapine per day had no beneficialeffect.

The child was referred to us in February 1999, whenwe observed dramatic dystonic spasms involving alllimbs and trunk, associated with ballismus. We judgedhis condition to be life-threatening and admitted him toour intensive-care unit, where artificial respiration wasgiven under continuous sedation (propofol). Triple

A videotape accompanies this article.Received July 12, 1999; revision received October 6, 1999. Accepted

April 4, 2000.Address correspondence and reprint requests to Lucia Angelini, MD,

Department of Neuropediatrics, National Neurological Institute“C. Besta,” Via Celoria 11, 20133 Milan, Italy.

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therapy with anticholinergics, a dopamine depletor, and adopamine receptor-blocker was introduced with increas-ing dosage (up to 10 mg trihexyphenidyl, 125 mg tetra-benazine, and 20 mg pimozide per day). Sedation wassuspended every 4 days to monitor movements but nocontrol was observed. A single injection of intrathecalbaclofen was also tried but was ineffective. We thereforedecided to apply deep brain stimulation.

The day before surgery the patient underwent mag-netic resonance (MR) examination with a T1 protocol.On the day of surgery, under general anesthesia, a CRWframe (Radionics, Burlington, MA, USA) was positionedon the head and a computed tomography (CT) scan wasperformed in stereotactic conditions. The geometricallyaccurate CT images were passed to the workstation forimage fusion (Stereoplan, Radionics), with the anatomi-cally accurate MR images, to determine the coordinatesof the implantation sites. A possible target for basal nu-clei stimulation (GPi) was identified on the fused imagesand its position was verified on a stereotactic anatomicatlas available as software.

The coordinates of the target were then transferred tothe CRW frame in the operating room. The patientwas not curarized to permit observation of clinicalresponses to the introduction of the electrode and stimu-lation. A Siegfried-type electrode (Radionics) was in-serted stereotactically to verify the efficacy of stimula-tion at the calculated target and to create a passage for aquadripolar electrode (Medtronic, Minneapolis, MN,USA) that was inserted shortly thereafter. Using differentpole stimulation combinations, nearby structures (inter-nal capsule and optic tract) were investigated, the effi-cacy of stimulation was clinically confirmed, and post-operative MRI was performed to check the position ofthe electrode; no intraoperative electrophysiological re-cording was performed.

Within a week, sedation with propofol had beenstopped and autonomous respiration was possible. A testperiod of stimulation was performed by using an externaltemporary stimulator, thus resulting in marked improve-ment of the abnormal movements. A progressive de-crease of drug therapy up to its withdrawal was possibleas well. Switching off the test stimulation resulted in thesudden reappearance of the abnormal movements. There-fore, again under general anesthesia, the permanent pulsegenerator was implanted subcutaneously in the supracla-vicular space. Over the next 3 weeks all pharmacologictreatment was discontinued, and pulse with stimulationfrequencies and current intensities were adjusted, moni-toring neurologic manifestations to optimize the benefi-cial effect.

In the present case, after successful permanent implan-tation of the stimulator and optimization of the stimu-lation parameters, the child’s neurologic conditioncontinued to improve. He regained autonomous walking.Mild dystonic postures of the arms and legs and low-amplitude dyskinesias in the arms, mainly on the right,persisted. Talking became possible, although moder-ate dysarthria was still present. During this period,repetitive tests of stimulation at different parametersand with stimulators off confirmed the efficacy andright positioning of electrodes by reducing abnormalmovements.

Following implantation, investigations for the differ-ential diagnosis of the progressive symptomatic dystoniacontinued. All resulted in normal results. CT andMRI were unrevealing. However, more recently, assayof biogenic amine metabolites and pterins in cerebro-spinal fluid showed extremely low 5HIAA and HVAlevels, together with low 5HIAA/HVA ratio, suggest-ing tyrosine hydroxylase deficiency. DNA analysis fora mutation in the gene coding for this enzyme is inprogress.

After 7 months of follow up, the boy is able to walkindependently, can speak audibly, and can eat indepen-dently (see the videotape). All medication has been dis-continued. Residual dystonic signs and symptoms aremilder than those present before the dramatic worseningof his neurologic condition.

DISCUSSION

Posterior internal pallidal ablation (GPi pallidotomy)was introduced to treat intractable parkinsonian symp-toms.3,4 Recently, unilateral and bilateral pallidotomyhas been proposed for medically refractory primary andsecondary dystonia.5,6

Pallidotomy offers advantages over thalamotomy,which has been traditionally used for the surgical treat-ment of dystonia. The pallidal target (sensorimotorportion of the GPi) is somatotopically better definedthan targets in the motor thalamus, and the risk of dys-arthria, dysphagia, weakness, and sensory loss often as-sociated with thalamotomy is lower. Furthermore, unlikethalamotomy which blocks the pallidal-cerebellar-thalamic-cortical loop, a pallidotomy that may blockneuronal input to the peduncolopontine nucleus and re-ticulospinal tract may also allow control of otherwiseunresponsive axial muscles that are involved in general-ized dystonia.7

The satisfactory results of pallidotomy have been con-firmed by the newer technique of bilateral chronic elec-trostimulation of the ventrolateral pallidum,8,9 mainlyused to treat parkinsonian, essential, and cerebellar trem-

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ors. Unlike pallidotomy, this approach is both nonde-structive and reversible, and the unwanted side effectsfrequently associated with bilateral ablative proceduresare probably less severe. Therefore, notwithstanding thehigh cost of bilateral implants, pallidal stimulation maybe an attractive alternative to pallidotomy.

LEGENDS TO THE VIDEOTAPESegment 1(in the intensive-care unit): Generalized,

severe dystonic dyskinesias on discontinuation ofpropofol.

Segment 2 (1 week after surgery): Oromandibulardyskinesias and mild-to-moderate dystonic dyskinesiasof both arms and the right leg.

Segment 3(3 weeks after surgery): Further improve-ment of the movement disorder; there is restoration ofwalking ability with slight support and of intelligiblespeech.

Segment 4(2 months after surgery): The boy returnsto everyday life. He is able to walk autonomously andpresents satisfactory motor skills.

Acknowledgments: The authors thank Dr. F. Bouquet,Dept. of Neuropediatrics, Burlo-Garofalo Hospital, Trieste,Italy, for referring the patient, and Dr. Donald Ward for revis-ing the English version of the manuscript.

REFERENCES

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2. Manji H, Howard RS, Miller DH, et al. Status dystonicus: thesyndrome and its management.Brain 1998;121:243–252.

3. Baron MS, Vitek JL, Bakay RAE, et al. Treatment of advancedParkinson’s disease by posterior GPi pallidotomy: 1-year results ofa pilot study.Ann Neurol1996;40:355–366.

4. Lang AE, Lonzano A, Montgomery E, et al. Posteroventral medialpallidotomy in advanced Parkinson’s disease.N Engl J Med1997;337:1036–1042.

5. Ondo WG, Desaloms JM, Jankovic J, Grossman RG. Pallidotomyfor generalized dystonia.Mov Disord1998;13:693–698.

6. Vitek JL, Zhang J, Evatt M, et al. GPi pallidotomy for dystonia:clinical outcome and neuronal activity.Adv Neurol1998;78:211–219.

7. Broggi G. Chronic deep brain stimulation: clinical results. In:Germano IM, ed.Neurosurgical Treatment of Movement Disor-ders. Neurosurgical Topics.Park Ridge, IL: American Associationof Neurological Surgeons, 1998:169–175.

8. Siegfried J, Lippitz B. Bilateral chronic electrostimulation of ven-troposterolateral pallidum: a new therapeutic approach for allevi-ating all parkinsonian symptoms.Neurosurgery1994;35:1126–1130.

9. Tronnier VM, Fogel W, Kronenbuerger M, Steinvorth S. Pallidalstimulation: an alternative to pallidotomy?J Neurosurg1997;87:700–705.

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