Ainhi D. Ha

Huntington's disease.

PURPOSE OF REVIEW This review highlights the recent advances in Huntingtons disease, with particular focus on clinical characterization of prodromal Huntingtons disease, as well as the growing literature regarding pathophysiological mechanisms and their relevance to potential therapeutic targets. RECENT FINDINGS Clinical and neuroradiological abnormalities can be demonstrated in gene-positive individuals prior to the onset of manifest Huntingtons disease, even as far as 15 years before the disease onset. Although some measures show promise as potential markers of disease progression, further longitudinal studies are required. Several molecular pathways have been implicated in the process of neurodegeneration involved in Huntingtons disease and provide potential therapeutic targets. SUMMARY With predictive testing allowing the identification of gene-positive individuals prior to disease onset, the prodromal stage of Huntingtons disease provides an ideal period for the use of disease-modifying therapy. A quantifiable and reliable biomarker for monitoring disease progression is crucial for clinical studies of neuroprotection, and this remains an area of active research. Understanding of the underlying pathophysiological mechanisms continues to grow, based mainly on cellular and animal models of Huntingtons disease.

The phenotypic spectrum of dystonia in Mohr–Tranebjaerg syndrome

Mohr–Tranebjaerg syndrome (MTS) is an X‐linked recessive disorder characterized by deafness and dystonia. However the phenotypic expression of dystonia has not been systematically defined. We report clinical, neurophysiological, and ophthalmological data on 6 subjects from 3 Australian kindreds, including 2 with novel mutations, together with a systematic review of the literature, in order to define the phenotypic expression of dystonia. Profound hearing impairment in affected males develops by infancy and precedes the development of dystonia, which varies in time of onset from the first to the sixth decades, with a peak in the second and third decades. Dystonia in MTS tends to be focal, segmental, or multifocal in distribution at onset, with a predilection for the upper body, variably involving the head, neck, and upper limbs. The majority of patients have progression or generalization of their dystonia regardless of age of onset. Within our 3 kindreds, we observed relative intrafamilial homogeneity but interfamilial variation. The median time to the development of moderate‐severely disabling dystonia in these subjects was 11 years. Associated features included progressive cognitive decline, pyramidal signs, and in 1 patient, gait freezing and postural instability. Optic atrophy and cortical visual impairment were both observed. We report for the first time a female patient who developed multiple disabling neurological complications of MTS. Our findings more clearly define and expand the phenotype of both the dystonia and other neurological features of MTS and have implications for the diagnosis and management of this condition.

Dramatic improvement of truncal tardive dystonia following globus pallidus pars interna deep brain stimulation.

Truncal predominant tardive dystonia is an uncommon presentation of dystonia, and may be associated with significant disability. We report a patient with near-complete resolution of severe, disabling truncal tardive dystonia following globus pallidus pars interna deep brain stimulation. Her unusual clinical presentation highlights the difficulties in diagnosing unusual forms of dystonia, and the therapeutic gains that can be achieved once the diagnosis is recognised.

Movement disorders associated with CLIPPERS

Case 1 A woman aged 65 years developed subacute right upper limb tremor and dystonia associated with progressive gait ataxia, dysarthria, vertigo, lethargy and confusion. Examination revealed right upper limb rest tremor predominantly affecting the forearm, moderate intention tremor, and intermittent postural tremor accompanied by dystonic posturing (see Video Segment 1). There was mild dystonia of the right leg during walking. Surface electromyography (EMG) recordings revealed 3-Hz to 4-Hz EMG bursting in the right upper limb muscles. A cerebral magnetic resonance image (MRI) demonstrated contrast-enhancing lesions in the bilateral brachium pontis, pons, and cerebellum, typical of CLIPPERS, in addition to high signal in the right dentate nucleus (Fig. 1A,B). Cerebellar biopsy demonstrated a perivascular, lymphohistiocytic, inflammatory infiltrate and reactive gliosis. Treatment with high-dose corticosteroids lead to dramatic clinical and radiological improvement, although the tremor persisted. Treatment with a combination of levodopa and botulinum toxin injections resulted in marked symptomatic and functional improvement of tremor.

Neurophysiological Features Of Hemiballism

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Resolution of Othello Syndrome After Subthalamic Nucleus Deep Brain Stimulation in 3 Patients with Parkinson's Disease

Psychiatric symptoms are historically thought a relative contraindication to DBS for advanced Parkinsons disease (PD). However, in the case of drug‐induced mental illness, DBS may provide an acceptable alternative for the treatment of motor symptoms. This allows reduction of pharmacological dopaminergic therapy that might otherwise cause negative psychiatric consequences. For example, DBS is increasingly used to ameliorate specific complications of PD treatment, such as impulse control disorders. We present a series of 3 cases of young male patients who developed Othello syndrome (OS) during treatment with dopamine agonists. In each case, the OS resolved with withdrawal of the offending drug. Subsequent treatment with bilateral STN DBS improved motor symptoms and allowed reduction in their dopaminergic drug regimen. We therefore propose that drug‐induced psychopathology may be an indication (rather than a contraindication) for DBS in selected cases.