Dystonia, defined as a neurological syndrome characterised by involuntary, patterned, sustained, or repetitive muscle contractions of opposing muscles, causing twisting movements and abnormal postures, is one of the most disabling movement disorders. Although gene mutations and other causes are increasingly recognised, most patients have primary dystonia without a specific cause. Although pathogenesis-targeted treatment is still elusive, the currently available symptomatic treatment strategies are quite effective for some types of dystonia in relieving involuntary movements, correcting abnormal posture, preventing contractures, reducing pain, and improving function and quality of life. A small portion of patients have a known cause and respond to specific treatments, such as levodopa in dopa-responsive dystonia or drugs that prevent copper accumulation in Wilson's disease. Therapeutic options must be tailored to the needs of individual patients and include chemodenervation with botulinum toxin injections for patients with focal or segmental dystonia, and medical treatments or deep brain stimulation for patients with generalised dystonia.

https://www.thelancet.com/pdfs/journals/laneur/PIIS1474-4422(06)70574-9.pdf

Treatment of dystonia

Object. The aim of this study was to evaluate the long-term safety and efficacy of bilateral contemporaneous deep brain stimulation (DBS) in patients who have levodopa-responsive parkinsonism with untreatable motor fluctuations. Bilateral pallidotomy carries a high risk of corticobulbar and cognitive dysfunction. Deep brain stimulation offers new alternatives with major advantages such as reversibility of effects, minimal permanent lesions, and adaptability to individual needs, changes in medication, side effects, and evolution of the disease. Methods. Patients in whom levodopa-responsive parkinsonism with untreatable severe motor fluctuations has been clinically diagnosed underwent bilateral pallidal magnetic resonance image—guided electrode implantation while receiving a local anesthetic. Pre- and postoperative evaluations at 3-month intervals included Unified Parkinson's Disease Rating Scale (UPDRS) scoring, Hoehn and Yahr staging, 24-hour self-assessments, and neuropsychological examinations. Six pati...

Efficiency and safety of bilateral contemporaneous pallidal stimulation (deep brain stimulation) in levodopa-responsive patients with Parkinson's disease with severe motor fluctuations: a 2-year follow-up review

Objective—To characterise postural tremors in patients with Parkinson’s disease. Rest tremor is a well recognised cardinal symptom of Parkinson’s disease, but postural tremors associated with the disease may cause more disability than the more typical rest tremor. Postural tremor of Parkinson’s disease has been attributed to enhanced physiological tremor, clonus, or coexistent essential tremor. It is postulated that one type of postural tremor in Parkinson’s disease represents a rest tremor that re-emerges after a variable delay while maintaining posture, hence “re-emergent tremor”. Methods—Accelerometry, peak frequency, peak frequency amplitude, root mean square (RMS) amplitude,and latency were determined in 18 patients (mean age: 63.2 (SD 9.8) years) with Parkinson’s disease who had clinically evident postural tremor, 20 (mean age: 66.9 (SD 5.8) years) with typical essential tremor, and seven (mean age: 68.7 (SD 15.3) years) with the combination of pre-existing essential tremor and subsequent Parkinson’s disease (essential tremor/Parkinson’s disease). Latency, the time interval starting with the assumption of an outstretched posture and ending with the onset of postural tremor, was measured by marking the start time by a pulse produced from interrupting a beam to a photocell when the arm reached a horizontal position. Results—The latency for the re-emergent tremor (9.37 (SD 10.66) s), present in 12 of 18 patients with Parkinson’s disease, was significantly (p<0.0005) longer than the latency for postural tremor of essential tremor (1.29 s in one patient, absent in 19 others); five of seven essential tremor/ Parkinson’s disease patients had an observed latency (6.57 (SD 8.23 s) which was also significantly (p<0.005) longer than that for essential tremor. There was no diVerence in the mean tremor frequency (~5.5 Hz) between the re-emergent tremor and the more typical Parkinson’s disease rest tremor. The amplitudes were generally higher for the postural tremor associated with Parkinson’s disease compared with those of essential tremor. Conclusion—These studies suggest that the re-emergent tremor of Parkinson’s disease can be diVerentiated from the postural tremor of essential tremor and that it may share pathophysiological mechanisms with the more typical rest tremor. (J Neurol Neurosurg Psychiatry 1999;67:646‐650)

https://jnnp.bmj.com/content/jnnp/67/5/646.full.pdf

Re-emergent tremor of Parkinson’s disease

To consider whether the various clinical types of primary late-onset dystonia have a common aetiological background, or are each distinct and separate entities, sharing only the clinical appearance of dystonia, we reviewed epidemiological, clinical, neurophysiological and imaging data reported in patients with different forms of primary late-onset dystonia. The epidemiological and clinical features that distinguished the various clinical types and suggest aetiological differences were prevalence, age of onset, sex preference, sensory tricks, and tendency to spread. Likewise, aetiological differences were also supported by the observation that environmental risk factors possibly triggering focal dystonias in predisposed subjects can differ from one form to the other. The fact that different forms of focal dystonia may coexist in the same individual as the result of spread nevertheless suggests that the various focal dystonias are related. Detailed examination of available familial and genetic data indicates that the different forms of primary late-onset dystonia share aetiological factors, most probably genetic. Neurophysiological and imaging studies have demonstrated a number of abnormalities in focal dystonias and some of these are shared by the different clinical types. The shared abnormality of sensorimotor integration (and cortical excitability) beyond the symptomatic body part identified in various clinical types and in unaffected relatives might reflect the genetic abnormality indicating the substrate on which the dystonia develops.

/pdf/do-primary-adult-onset-focal-dystonias-share-aetiological-3r7et2eh21.pdf

Do primary adult-onset focal dystonias share aetiological factors?

Surgical options for Parkinson's disease (PD) are rapidly expanding and include ablative procedures, deep brain stimulation, and cell transplantation. The target nuclei for ablative surgery and deep brain stimulation are the motor thalamus, the globus pallidus, and the subthalamic nucleus. Multiple factors have led to the resurgence of interest in the surgical treatment of PD: 1) recognition that long-term medical therapy for PD is often unsatisfactory, with patients eventually suffering from drug-induced dyskinesias, motor fluctuations, and variable responses to medication; 2) greater understanding of the pathophysiology of PD, providing a better scientific rationale for some previously developed procedures and suggesting new targets; and 3) use of improved techniques, such as computed tomography- and magnetic resonance imaging-guided stereotaxy and single-unit microelectrode recording, making surgical intervention in the basal ganglia more precise. We review the present status of ablative surgery and deep brain stimulation for PD, including theoretical aspects, surgical techniques, and clinical results.

Ablative surgery and deep brain stimulation for Parkinson's disease.

OBJECTIVES—Oromandibular dystonia (OMD) is a focal dystonia manifested by involuntary muscle contractions producing repetitive, patterned mouth, jaw, and tongue movements. Dystonia is usually idiopathic (primary), but in some cases it follows peripheral injury. Peripherally induced cervical and limb dystonia is well recognised, and the aim of this study was to characterise peripherally induced OMD.
METHODS—The following inclusion criteria were used for peripherally induced OMD: (1) the onset of the dystonia was within a few days or months (up to 1 year) after the injury; (2) the trauma was well documented by the patient's history or a review of their medical and dental records; and (3) the onset of dystonia was anatomically related to the site of injury (facial and oral).
RESULTS—Twenty seven patients were identified in the database with OMD, temporally and anatomically related to prior injury or surgery. No additional precipitant other than trauma could be detected. None of the patients had any litigation pending. The mean age at onset was 50.11 (SD 14.15) (range 23-74) years and there was a 2:1 female preponderance. Mean latency between the initial trauma and the onset of OMD was 65 days (range 1 day-1 year). Ten (37%) patients had some evidence of predisposing factors such as family history of movement disorders, prior exposure to neuroleptic drugs, and associated dystonia affecting other regions or essential tremor. When compared with 21 patients with primary OMD, there was no difference for age at onset, female preponderance, and phenomenology. The frequency of dystonic writer's cramp, spasmodic dysphonia, bruxism, essential tremor, and family history of movement disorder, however, was lower in the post-traumatic group (p<0.05). In both groups the response to botulinum toxin treatment was superior to medical therapy (p<0.005). Surgical intervention for temporomandibular disorders was more frequent in the post-traumatic group and was associated with worsening of dystonia.
CONCLUSION—The study indicates that oromandibular-facial trauma, including dental procedures, may precipitate the onset of OMD, especially in predisposed people. Prompt recognition and treatment may prevent further complications.

https://jnnp.bmj.com/content/jnnp/65/5/722.full.pdf

Peripherally induced oromandibular dystonia

Despite a paucity of controlled data, stereotactic pallidotomy is increasingly used for the treatment of advanced Parkinson's disease (PD). To study the efficacy of the procedure on the cardinal PD features of rigidity, tremor, bradykinesia, and postural instability, we blindly rated randomized videos of 34 patients recorded in the "off' state immediately before and 3 months after unilateral stereotactic lesioning of the globus pallidus internus. Total "off' time Unified Parkinson's Disease Rating Scale motor scores improved 13.6% from 28.9 +/- 7.5 to 25.0 +/- 7.0 (p < 0.001). Particularly robust improvement was seen in contralateral tremor, gait, and arising from a chair (p < 0.001). Significant improvement was also seen in ipsilateral tremor, contralateral and some ipsilateral dexterity measures, and body bradykinesia. Most other features tended toward improvement but did not reach statistical significance. We conclude that pallidotomy is a safe and effective treatment of parkinsonian symptoms, many of which improve bilaterally.

Assessment of motor function after stereotactic pallidotomy

Immunoresistance (Ab+) to botulinum toxin type A (BTX-A) has been a serous concern since the introduction of BTX-A in the treatment of dystonia and other disorders associated with abnormal muscle contractions. We studied seven patients who developed Ab+ and later reverted to antibodynegative (Ab-) status. These seven patients, six women (mean age, 56 years; range, 41–80 years), with an average duration of dystonia for all patients of 197 months (range, 84–360 months), received a total mean cumulative dose of 1659 units (U) (range,810-1975 U), with an average dose of 207 U per visit. All of these patients became unresponsive to BTX-A treatment and became Ab+ as determined by mouse bioassay. Their response to BTX-A after they revertedd to Ab- was analyzed. The average latency between the initial BTX-A treatment and development of Ab+ was 27 months (range, 15–43 months). The average duration between the detection of Ab+ status and subsequent reversal to Ab- status was 30 months (range, 10–78 months). Six of these Ab- patients were reinjected with BTX-A, and all six benefited from repeat injections comparable with their earlier response. Three patients lost their clinical response to subsequent injections and were found to be again Ab+. Two of the five patients who became immunoresistant to BTX-A received botulinum toxin type F (BTX-F) injections and one patient received a single session of BTX-B with improvement in their symptoms. In conclusion, this unique group of patients who were Ab+ and became Ab- responded favorably to repeat BTX-A injections, but some lost the benefit with subsequent injections. These observations suggest that the anamnestic immunologic response to BTX-A can wane, but can be reactivated by repeat BTX-A treatments. The presence of antibodies did not interfere with the response to BTX-F or BTX-B injections, thus confirming the antigenic specificity of various BTX serotypes.

Variability of the immunologic and clinical response in dystonic patients immunoresistant to botulinum toxin injections

Adverse events of dopamine-blocking agents include acute dystonic reactions and oculogyric crises (OGCs). OGCs may be recurrent on maintenance of or re-exposure to the drug. Thus, complete withdrawal is recommended. Recurrent episodes of acute dystonia despite withdrawal and the lack of further exposure to antidopaminergic agents are usually not seen. Here, we report three cases with recurrent OGCs despite complete withdrawal of neuroleptics. Triggering or priming factors were a single dose of haloperidol in two cases and a single dose of metoclopramide in one case. Episodes reoccurred spontaneously, but responded to anticholinergics. The pathomechanisms of acute dystonic reactions and OGCs remain unclear. Parallels to levodopa-induced dyskinesias in Parkinson's disease, as well as to dopa-responsive dystonia, paroxysmal dyskinesias, and channelopathies are discussed here. Whether there is a genetic susceptibility or some other reason for only some patients developing this phenomenon remains unclear.

Recurrent acute dystonic reaction and oculogyric crisis despite withdrawal of dopamine receptor blocking drugs.

https://www.pedneur.com/article/S0887-8994(12)00020-3/pdf

Charulata Sankhla

Papers

Peripherally induced oromandibular dystonia

Assessment of motor function after stereotactic pallidotomy

Variability of the immunologic and clinical response in dystonic patients immunoresistant to botulinum toxin injections

Recurrent acute dystonic reaction and oculogyric crisis despite withdrawal of dopamine receptor blocking drugs.

Nonparaneoplastic anti-N-methyl-D-aspartate receptor encephalitis: a case series of four children.