Refractory status dystonicus in ataxia telangiectasia
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.198206
Source of Support: None, Conflict of Interest: None
Status dystonicus (SD), also termed as “dystonic storm,” is defined as increasingly frequent and severe episodes of generalized dystonia, requiring medical attention at the earliest. Penn and Jankovic described this rare condition in the year 1982. SD is the severe and life threatening stage of evolution of primary or secondary dystonia. The risk of a dystonic storm developing is directly proportional to the severity of dystonia. To the best of our knowledge, this is the first report of ataxia telangiectasia (AT) presenting as refractory status dystonicus.
A 10-year-old boy presented in 2012 with a history of abnormal limb movements since the age of 2 years. He was the first born child of a nonconsanguineous marriage with a normal antenatal history. He developed imbalance on walking at 18 months of age with upper limb incoordination and an abnormal dystonic neck posturing. Gait imbalance worsened over time and he also developed recurrent chest infections. The parents noticed redness of his eyes at this time. There was no history of jaundice, skeletal deformities, seizures, myoclonus, drop attacks or mental retardation.
On general examination, the patient was conscious and alert and did not have any dysmorphic features. Neurological examination showed features of pan-cerebellar ataxia, oculomotor apraxia, ocular telangiectasia [Figure 1], and slow saccades with broken pursuits. Deep tendon reflexes were normal and the plantar reflex was flexor.
Investigations showed a serum alfa-feto protein level of 67 ng/dl. He was diagnosed as having AT based on these features.
In 2014, he presented to the emergency department of our hospital for the second time with worsening of abnormal posturing of the neck and trunk, with dystonic spasms associated with pain for 4 months. The patient was bedridden and had severe dystonic posturing of both upper limbs and trunk. On examination, he was drowsy, afebrile, with intermittent dystonic spasms, and ophistonous posturing. Deep tendon reflexes were absent in the lower limb. Magnetic resonance imaging (MRI) of the brain, done in 2014, was normal. The CD4 count was 804 cells/cumm. Creatinine kinase was 852 IU/L. His cerebrospinal fluid examination was normal.
He was started on haloperidol 4 mg, lorazepam 6 mg, baclofen 10 mg, and trihexylphenidyl (THP) 6 mg daily dose. He developed fever on the second day of the admission and was started on antibiotics and antipyretics. However, the patient did not show any improvement; baclofen was increased to 40 mg, levodopa to 400 mg, and THP to 6 mg dose, with addition of pimozide 8 mg in a daily dosage schedule. Gabapentin 300 mg/day was also added to the regimen. In view of his poor response and worsening sensorium, the patient was intubated and started on parenteral lorazepam, propofol, and thiopentone infusion, and THP was increased to 18 mg/day. The patient showed a mild response to thiopentone infusion, but redeveloped recurrent spasms on tapering the medication. Fentanyl, haloperidol (15 mg per day), levetiracetam, clonidine, phenytoin, and midazolam were also tried. On the basis of anecdotal reports in literature, 1 gm methylprednisolone, in a single dose, and tetrabenazine 75 mg/day were also given. The patient continued to have incessant ophistonous posturing.
Since the child was resistant to pharamacological treatment, surgical treatment was attempted. He, therefore, underwent a bilateral pallidotomy in an attempt to relieve the dystonic spasms. Following the procedure, he was free of dystonia on the first postoperative day, but developed a recurrence the very next day. Another pulse of methylprednisolone was given after the pallidotomy; however, the patient did not respond to the medication. He was subsequently discharged and succumbed to his illness.
The first case of SD was described in an 8-year-old boy who was previously diagnosed to be having primary dystonia. This patient had developed complications of SD namely myoglobinuria, acute renal failure, and secondary hyperpyrexia. SD has been reported to progress from secondary dystonia in Wilson's disease, Batten disease More Details, pantothenate kinase associated degeneration, juvenile cerebral palsy, and striatal necrosis. The precipitating factors in SD are trauma, surgery, infection, and an abrupt introduction or cessation of dopaminergic medication. However, in many cases reports, the precipitating factors remain elusive, as was seen in our patient.
Intubation and mechanical ventilation, treatment of the triggering factors, and administration of anti-dystonia medication are the standard therapies being administered in SD. Intravenous sedation has been suggested as the first line treatment in the management of SD in view of its rapid and effective response. Midazolam is the drug of choice for intravenous sedation. Propofol may be given with regular monitoring, if the patient does not respond to midazolam. The factors influencing SD are dictated by the phenotype; the male gender and the tonic form of SD are associated with a worse prognosis when compared to the female gender and the phasic form of SD. Static diseases appear to have a higher likelihood of progressing to SD than progressive diseases.
Neurodegenerative disorders resulting in secondary dystonia respond poorly to conventional treatment. In these cases, intrathecal baclofen (ITB) may be tried. Grosso et al., reported a child with SD, having an underlying athetoid cerebral palsy, who responded excellently to ITB when other drugs had failed.
Surgical procedures are the only effective alternative treatment options for drug-resistant dystonic storms [Table 1]. Thalamotomy and pallidotomy were initially done in SD; however, with the advent of deep brain stimulation (DBS), lesioning surgeries are rarely being practiced. The youngest patient, in whom DBS has been done, is a 5-year-old boy with bilateral pallidal calcification. DBS has given an excellent outcome in refractory SD. In view of its absolute success, DBS has been proposed as the first line of treatment in SD, as an emergency surgery, in order to prevent the onset of complications of the ongoing SD from setting in. Pallidal DBS has been shown to cause a dramatic improvement in primary dystonia; however, the improvement achieved is variable in secondary dystonia. Andrew et al., reported post-thalamotomy improvement in only 25% of his patients with dystonia. Pallidotomy has clearly been more valuable in alleviating the symptoms of primary dystonia compared to a thalamotomy. However, secondary dystonia responds equally to both a thalamotomy and pallidotomy. Patients with hemidystonia apparently benefit more from a thalamotomy than patients with generalized dystonia. The complications of a thalamotomy include hemiparesis, dysarthria and hydrocephalus whereas that of pallidotomy include visual field defects, speech disorder, hypersomnia, seizures, dysphagia, and rarely coma., A staged bilateral pallidotomy is preferable to a simultaneously performed bilateral pallidotomy in view of lesser complications associated with the former.
Hence, bilateral pallidotomy can be an effective substitute when DBS is unavailable. Bilateral pallidotomy completely resolved refractory SD in a child with PANK2 mutation. Another study by Teive et al., reported a significant improvement in a child with SD after bilateral pallidotomy. However, our patient failed to respond immediately to bilateral pallidotomy. The effect of pallidotomy on dystonia may not be immediate and several weeks of observation might be needed to ascertain the success of the procedure. However, in life threatening SD, as in our patient, a multi-target ablation, that is, staged bilateral stereotactic pallidothalamotomy, must be considered, if the patient fails to respond to mono-target ablation. However, this could not be performed in our patient.
An aggressive approach needs to be adopted while treating patients with SD where the outcome might still be poor. DBS may be tried at the earliest in patients with SD. If DBS cannot be done, staged pallidotomy and thalamopallidotomy must be attempted in life threatening drug refractory SD.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.