Dystonia, chorea, hemiballismus and other dyskinesias.

Hyperkinesias are heterogeneous involuntary movements that significantly differ in terms of clinical and semeiological manifestations, including rhythm, regularity, speed, duration, and other factors that determine their appearance or suppression. Hyperkinesias are due to complex, variable, and largely undefined pathophysiological mechanisms that may involve different brain areas. In this chapter, we specifically focus on dystonia, chorea and hemiballismus, and other dyskinesias, specifically, levodopa-induced, tardive, and cranial dyskinesia. We address the role of neurophysiological studies aimed at explaining the pathophysiology of these conditions. We mainly refer to human studies using surface and invasive in-depth recordings, as well as spinal, brainstem, and transcortical reflexology and non-invasive brain stimulation techniques. We discuss the extent to which the neurophysiological abnormalities observed in hyperkinesias may be explained by pathophysiological models. We highlight the most relevant issues that deserve future research efforts. The potential role of neurophysiological assessment in the clinical context of hyperkinesia is also discussed.

Psychedelic-assisted therapy for functional neurological disorders: A theoretical framework and review of prior reports.

Functional neurological disorders (FNDs), which are sometimes also referred to as psychogenic neurological disorders or conversion disorder, are common disabling neuropsychiatric disorders with limited treatment options. FNDs can present with sensory and/or motor symptoms, and, though they may mimic other neurological conditions, they are thought to occur via mechanisms other than those related to identifiable structural neuropathology and, in many cases, appear to be triggered and sustained by recognizable psychological factors. There is intriguing preliminary evidence to support the use of psychedelic-assisted therapy in a growing number of psychiatric illnesses, including FNDs. We review the theoretical arguments for and against exploring psychedelic-assisted therapy as a treatment for FNDs. We also provide an in-depth discussion of prior published cases detailing the use of psychedelics for psychosomatic conditions, analyzing therapeutic outcomes from a contemporary neuroscientific vantage as informed by several recent neuroimaging studies on psychedelics and FNDs.

Treatment of Dystonia: Medications, Neurotoxins, Neuromodulation, and Rehabilitation.

Dystonia is a complex disorder with numerous presentations occurring in isolation or in combination with other neurologic symptoms. Its treatment has been significantly improved with the advent of botulinum toxin and deep brain stimulation in recent years, though additional investigation is needed to further refine these interventions. Medications are of critical importance in forms of dopa-responsive dystonia but can be beneficial in other forms of dystonia as well. Many different rehabilitative paradigms have been studied with variable benefit. There is growing interest in noninvasive stimulation as a potential treatment, but with limited long-term benefit shown to date, and additional research is needed. This article reviews existing evidence for treatments from each of these categories. To date, there are many examples of incomplete response to available treatments, and improved therapies are needed.

Current and emerging strategies for treatment of childhood dystonia.

Childhood dystonia is a movement disorder characterized by involuntary sustained or intermittent muscle contractions causing twisting and repetitive movements, abnormal postures, or both (Sanger et al, 2003). Dystonia is a devastating neurological condition that prevents the acquisition of normal motor skills during critical periods of development in children. Moreover, it is particularly debilitating in children when dystonia affects the upper extremities such that learning and consolidation of common daily motor actions are impeded. Thus, the treatment and rehabilitation of dystonia is a challenge that continuously requires exploration of novel interventions. This review will initially describe the underlying neurophysiological mechanisms of the motor impairments found in childhood dystonia followed by the clinical measurement tools that are available to document the presence and severity of symptoms. Finally, we will discuss the state-of-the-art of therapeutic options for childhood dystonia, with particular emphasis on emergent and innovative strategies.

Auditory startle reflex and startle reflex to somatosensory inputs in generalized dystonia.

OBJECTIVE: Startle reflex is a generalized defense reaction after unexpected auditory, visual, or tactile stimuli. Auditory startle reflex (ASR) and startle reflex to somatosensory inputs (SSS) have never been studied in generalized dystonia. Here, we aimed to study the characteristics and changes of ASR and SSS in this group. METHODS: We have examined ASR and SSS in patients with generalized dystonia (n=11) and healthy subjects (n=25) under the same conditions. ASRs and SSSs were recorded over the orbicularis oculi (O.oc), sternocleidomastoid, biceps brachii (BB), and abductor pollicis brevis (APB) muscles after bilateral auditory stimulation and unilateral median nerve electrical stimulation at the wrist, respectively. RESULTS: Both ASR and SSS showed the same sequence of muscle activation in both groups. However, the presence rates over the APB and BB muscles after both modalities of stimuli were significantly higher in the generalized dystonia group. ASR did not habituate in the dystonia group. CONCLUSIONS: Both ASR and SSS are disinhibited, and both show a similar sequence of muscle recruitment in generalized dystonia. SIGNIFICANCE: Higher probabilities over caudal muscles probably depend on the higher excitability of motor neurons secondary to central modulation.

Clinical features, MRI brain, and MRS abnormalities of drug-naïve neurologic Wilson's disease.

BACKGROUND: Magnetic resonance imaging (MRI) helps in the diagnosis of neurologic Wilson's disease (WD). The literature regarding MR spectroscopy (MRS) and diffusion-weighted imaging (DWI) in WD is limited. OBJECTIVES: To evaluate the clinical features and neuroimaging findings in drug-naïve neurologic WD and to find correlation between clinical stage and disease duration with different imaging findings. MATERIALS AND METHODS: The study subjects included consecutive and follow-up neurologic WD patients attending movement disorder clinic. The initial clinical and MRI features before commencement of chelation therapy were noted. Of 78 patients, 34 underwent DWI study and MRS was done in 38 patients and in 32 control subjects. RESULTS: Dystonia, dysarthria, tremor, and behavioral abnormality were common presenting features. All patients had MRI abnormality with major affection of basal ganglia. The clinical severity and anatomical extent of MRI abnormalities were positively correlated (P < 0.001; r s = 0.709). Presence of diffusion restriction was inversely related to duration of disease (P < 0.001; r s = 0.760). WD patients had reduced N-acetylaspartate/creatine (Cr) and choline (Cho)/Cr ratio (P < 0.001) as compared with control subjects in MRS study. CONCLUSION: Dystonia, dysarthria and tremor are common neurological features of WD. In this study, MRI abnormalities were positively correlated with disease severity; diffusion restriction was inversely correlated with the duration of the disease process. MRS was also a sensitive tool for diagnosing patient of neurologic WD.

[Neuromuscular electric stimulation therapy in otorhinolaryngology]. / Neuromuskuläre Elektrostimulationsverfahren in der HNO-Heilkunde.

BACKGROUND: Animal experiments have shown that after specific nerve traumatization, neuromuscular electrostimulation (NMES) can promote nerve regeneration and reduce synkinesia without negatively interfering with normal regeneration processes. NMES is used routinely in physical rehabilitation medicine. METHODS: This systematic literature search in the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, the DAHTA database, the Health Technology Assessment Database and MEDLINE or PubMed considered studies on the use of NMES in otorhinolaryngology that have been published in German or English. RESULTS: The search identified 180 studies. These were evaluated and relevant studies were included in the further evaluation. DISCUSSION: In the fields of otorhinolaryngology and phoniatry/paediatric audiology, clinical studies investigating the effects of NMES on facial and laryngeal paresis, as well as dysphonia and dysphagia have been carried out. The evidence collected to date is encouraging; particularly for the treatment of certain forms of dysphagia and laryngeal paresis.

Sensory aspects of movement disorders.

Movement disorders, which include disorders such as Parkinson's disease, dystonia, Tourette's syndrome, restless legs syndrome, and akathisia, have traditionally been considered to be disorders of impaired motor control resulting predominantly from dysfunction of the basal ganglia. This notion has been revised largely because of increasing recognition of associated behavioural, psychiatric, autonomic, and other non-motor symptoms. The sensory aspects of movement disorders include intrinsic sensory abnormalities and the effects of external sensory input on the underlying motor abnormality. The basal ganglia, cerebellum, thalamus, and their connections, coupled with altered sensory input, seem to play a key part in abnormal sensorimotor integration. However, more investigation into the phenomenology and physiological basis of sensory abnormalities, and about the role of the basal ganglia, cerebellum, and related structures in somatosensory processing, and its effect on motor control, is needed.

EMG-based visual-haptic biofeedback: a tool to improve motor control in children with primary dystonia.

New insights suggest that dystonic motor impairments could also involve a deficit of sensory processing. In this framework, biofeedback, making covert physiological processes more overt, could be useful. The present work proposes an innovative integrated setup which provides the user with an electromyogram (EMG)-based visual-haptic biofeedback during upper limb movements (spiral tracking tasks), to test if augmented sensory feedbacks can induce motor control improvement in patients with primary dystonia. The ad hoc developed real-time control algorithm synchronizes the haptic loop with the EMG reading; the brachioradialis EMG values were used to modify visual and haptic features of the interface: the higher was the EMG level, the higher was the virtual table friction and the background color proportionally moved from green to red. From recordings on dystonic and healthy subjects, statistical results showed that biofeedback has a significant impact, correlated with the local impairment, on the dystonic muscular control. These tests pointed out the effectiveness of biofeedback paradigms in gaining a better specific-muscle voluntary motor control. The flexible tool developed here shows promising prospects of clinical applications and sensorimotor rehabilitation.

Thalamic neuronal and EMG activity in psychogenic dystonia compared with organic dystonia.

BACKGROUND: This is a retrospective analysis of thalamic neuronal and electromyogram activities between subjects with organic dystonia and a subject with psychogenic dystonia in whom a thalamotomy was carried out before the diagnosis of psychogenic dystonia was made. RESULTS: The signal-to-noise ratio in the lowest frequency band (dystonia frequency < 0.76 Hz) in the electromyogram was not significantly different by diagnosis or muscle. The coherence at dystonia frequency for wrist flexors X biceps electromyograms was significantly higher in organic dystonia, whereas the phase was not apparently different from zero for either diagnosis. In a thalamic pallidal relay nucleus (ventral oral posterior), neuronal firing rates were not apparently different between psychogenic and organic dystonia. The neuronal signal-to-noise ratio in ventral oral posterior was significantly higher in organic dystonia than in psychogenic dystonia, whereas both were greater than in controls with chronic pain. Spike X electromyogram coherence apparently was not different between psychogenic and organic dystonia. The proportion of thalamic cells responding to joint movements was higher in the cerebellar relay nucleus (ventral intermediate) of psychogenic dystonia than in organic dystonia. CONCLUSIONS: These results suggest that some features, such as firing rates and thalamic reorganization, are similar in psychogenic and organic dystonia. Other features differ, such as the coherence between the electromyograms from different muscles and the thalamic neuronal signal-to-noise ratio, which may reflect pathophysiological factors in organic dystonia. © 2011 Movement Disorder Society.

Psychogenic movement disorders.

Psychogenic movement disorders (PMDs) represent a challenging dilemma for the treating neurologist. The terminology to classify this disorder is confusing and making the diagnosis is difficult. Once the diagnosis has been established, treatment options are limited, and the patient generally does not accept the diagnosis.

"Dystonic" body perception in childhood dystonia.

Dystonia refers to a syndrome of sustained muscle contractions, frequently causing twisting and repetitive movements, or abnormal postures. Although the pathophysiology of the abnormal posture is still unknown and a wide variety of abnormal postures can be observed, recent psychophysical studies have revealed abnormalities in the way patients with focal and generalized dystonia judge the position of their bodies in space [Bove M, Brichetto G, Abbruzzese G, Marchese R, Schieppati M. Neck proprioception and spatial orientation in cervical dystonia. Brain 2004;127(Pt 12):2764-78; Molloy FM, Carr TD, Zeuner KE, Dambrosia JM, Hallett M. Abnormalities of spatial discrimination in focal and generalized dystonia. Brain 2003;126(Pt 10):2175-82; Anastasopoulos D, Nasios G, Psilas K, Mergner T, Maurer C, Lucking CH. What is straight ahead to a patient with torticollis? Brain 1998;121(Pt 1):91-101]. Most intriguingly, patients do not always recognize "straight ahead" in the way normal individuals do [Anastasopoulos D, Nasios G, Psilas K, Mergner T, Maurer C, Lucking CH. What is straight ahead to a patient with torticollis? Brain 1998;121(Pt 1):91-101]. We describe a patient with childhood-onset dystonia who consistently drew images of his unaffected family members with 'dystonic' postures without being aware that this posture is abnormal.

Oscillations in the basal ganglia under normal conditions and in movement disorders.

A substantial body of work within the last decade has demonstrated that there is a variety of oscillatory phenomena that occur in the basal ganglia and in associated regions of the thalamus and cortex. Most of the earlier studies focused on recordings in rodents and primates. More recently, significant advances have been made in this field of research through the analysis of basal ganglia field potentials recorded from implanted deep brain stimulation electrodes in the basal ganglia of human patients with Parkinson's disease and other disorders. It now appears that oscillatory activity may play a significant role in the pathogenesis of these diseases. The most significant finding is that in Parkinson's disease synchronized oscillatory activity in the 10- to 35-Hz band (often termed "beta-band") is prevalent in the basal ganglia-thalamocortical circuits, and that such activity can be reduced by dopaminergic treatments. The entrainment of large portions of these circuits may disrupt information processing in them and may lead to parkinsonian akinesia (and perhaps tremor). Although less firmly established than the role of oscillations in movement disorders, oscillatory activities at higher frequencies may also be a component of normal basal ganglia physiology.

Mutations in the gene encoding peroxisomal sterol carrier protein X (SCPx) cause leukencephalopathy with dystonia and motor neuropathy.

In this report, we describe the first known patient with a deficiency of sterol carrier protein X (SCPx), a peroxisomal enzyme with thiolase activity, which is required for the breakdown of branched-chain fatty acids. The patient presented with torticollis and dystonic head tremor as well as slight cerebellar signs with intention tremor, nystagmus, hyposmia, and azoospermia. Magnetic resonance imaging showed leukencephalopathy and involvement of the thalamus and pons. Metabolite analyses of plasma revealed an accumulation of the branched-chain fatty acid pristanic acid, and abnormal bile alcohol glucuronides were excreted in urine. In cultured skin fibroblasts, the thiolytic activity of SCPx was deficient, and no SCPx protein could be detected by western blotting. Mutation analysis revealed a homozygous 1-nucleotide insertion, 545_546insA, leading to a frameshift and premature stop codon (I184fsX7).

Motor conversion disorders reviewed from a neuropsychiatric perspective.

BACKGROUND: Conversion disorder is a somatoform disorder defined by the presence of pseudoneurologic symptoms relating to voluntary sensory or motor function. The correct diagnosis of conversion disorder presenting with motor symptoms is complicated by the lack of gold-standard diagnostic tests and the absence of a universally accepted set of positive diagnostic criteria. This article reviews the epidemiology, pathophysiology, presentation, differential diagnosis, treatment, and prognosis of motor conversion, placing emphasis on diagnostic validity, reliability, and utility, while evaluating the empirical evidence supporting diagnostic and treatment strategies. DATA SOURCES AND STUDY SELECTION: Literature searches were carried out in PubMed using the keywords conversion disorder, motor conversion, dystonia, psychogenic, hysteria, somatization, motion disorder, movement disorder, and patho-physiology. Articles and book chapters in the author's personal collection were also utilized. CONCLUSIONS: Advances in neuropsychiatric research are leading to significant improvements in the diagnosis and understanding of motor conversion disorders. Positive, objective, and quantitative diagnostic criteria show significant promise for enhancing diagnostic accuracy. Current pathophysiologic research has begun to provide mechanistic explanations for conversion symptoms, thus blurring the distinction between psychogenic and organic motor disorders.

Regional cerebral hyperperfusion with ictal dystonic posturing: ictal-interictal SPECT subtraction.

PURPOSE: Ictal-interictal single-photon emission computed tomography (SPECT) subtraction was performed to find brain structures related to ictal dystonic posturing (DP) in patients with temporal lobe epilepsy (TLE). METHODS: Thirty-two patients with mesial TLE who had ictal and interictal SPECTs were included. They were divided into two groups; DP group with ictal dystonia during ictal SPECT (n = 15) and Non-DP group without ictal DP (n = 17). Ictal-interictal SPECT subtraction was performed, and then subtracted SPECT was coregistered with brain spoiled gradient recalled (SPGR) magnetic resonance imaging (MRI). The ictal hyperperfusion on subtracted SPECT was analyzed in basal ganglia, frontal cortex, thalamus, temporal lobe, and insular cortex. RESULTS: The incidences of ictal hyperperfusion on brain regions in DP versus Non-DP groups were 80.0% (12 of 15 patients) versus none (0 of 17), p = 0.001, chi2, in caudate nucleus; 93.3% (14 of 15) versus 47.0% (eight of 17), p = 0.005, in putamen; and 80.0% (12 of 15) versus 41.2% (seven of 17), p = 0.026, in thalamus. No significant difference of ictal hyperperfusion was found in globus pallidus, temporal lobes, insular and frontal cortices between DP and Non-DP groups. DP patients showed an earlier age at seizure onset [8.6 years (DP) vs. 15.7 years (Non-DP) (p = 0.015)] and a longer duration of seizure history [19.0 years (DP) vs. 11.9 years (Non-DP) (p = 0.015)]. CONCLUSIONS: Caudate nucleus, putamen, and thalamus were significantly related to the ictal DP during TLE seizures. Our study showed first an active involvement of the caudate nucleus in the generation of ictal DP.

Dystonia in AIDS: report of four cases.

Dystonia is a rare complication of acquired immune deficiency syndrome (AIDS). We report four such cases related to three different causes. Cases 1 and 2 both developed dystonia secondary to biopsy-proven progressive multifocal leukoencephalopathy. One had left arm dystonia, whereas the other had bilateral upper limb dystonia. One patient had associated akinesia and rigidity. Imaging demonstrated frontal and/or parietal white matter lesions but no basal ganglia abnormalities. Case 3 developed hemidystonia and cervical dystonia from biopsy-proven toxoplasmosis with a lesion in the thalamus. Case 4 suffered from AIDS dementia complex and developed cervical dystonia while taking risperidone therapy. We also review previously reported cases of dystonia in AIDS patients with the same causes and discuss the issue of increased vulnerability of the basal ganglia to HIV infection which, in turn, leads to increased sensitivity to neuroleptics. When dystonia is seen in AIDS patients, its pattern may be a clue to the ultimate cause.

Transient dystonia following magnetic resonance imaging in a patient with deep brain stimulation electrodes for the treatment of Parkinson disease. Case report.

Data from previous studies have shown that magnetic resonance (MR) imaging of the head can be performed safely in patients with deep brain stimulators. The authors report on a 73-year-old patient with bilaterally implanted deep brain electrodes for the treatment of Parkinson disease, who exhibited dystonic and partially ballistic movements of the left leg immediately after an MR imaging session. Such dystonic or ballistic movements had not been previously observed in this patient. In the following months, this focal movement disorder resolved completely. This case demonstrates the possible risks of MR imaging in patients with deep brain stimulators.