Eating dysfunction associated with oromandibular dystonia: clinical characteristics and treatment considerations

BACKGROUND: In oromandibular dystonia (OMD) abnormal repetitive contractions of masticatory, facial, and lingual muscles as well as the presence of orobuccolingual (OBL) dyskinesias may interfere with the appropriate performance of tasks such as chewing and swallowing leading to significant dysphagia and weight loss. We present here the clinical characteristics and treatment variables of a series of patients that developed an OMD-associated eating dysfunction. METHODS: We present a series of patients diagnosed and followed-up at the Movement Disorders Clinic of the Department of Neurology of University of Miami, Miller School of Medicine over a 10-year period. Patients were treated with botulinum toxin injections according to standard methods. RESULTS: Five out of 32 (15.6%) OMD patients experienced symptoms of eating dysfunction associated with OMD. Significant weight loss was reported in 3/5 patients (ranged for 13–15 lbs). Two patients regained the lost weight after treatment and one was lost to follow-up. Tetrabenazine in combination with other antidystonic medication and/or botulinum toxin injections provided substantial benefit to the patients with dysphagia caused by OMD. CONCLUSION: Dystonic eating dysfunction may occasionally complicate OMD leading to weight loss. Its adequate characterization at the time of history taking and clinical examination should be part of outcome measurements of the anti-dystonic treatment in clinical practice

Intraprostatic Botulinum Toxin Type A injection in patients with benign prostatic enlargement: duration of the effect of a single treatment

<p>Abstract</p> <p>Background</p> <p>Botulinum Toxin Type-A (BoNT/A) intraprostatic injection can induce prostatic involution and improve LUTS and urinary flow in patients with Benign Prostatic Enlargement (BPE). However, the duration of these effects is unknown. The objective of this work was to determine the duration of prostate volume reduction after one single intraprostatic injection of 200U of Botulinum Toxin Type-A.</p> <p>Methods</p> <p>This is an extension of a 6 month study in which 21 frail elderly patients with refractory urinary retention and unfit for surgery were submitted to intraprostatic injection of BoNT/A-200U, by ultrasound guided transrectal approach. In spite of frail conditions, eleven patients could be followed during 18 months. Prostate volume, total serum PSA, maximal flow rate (Qmax), residual volume (PVR) and IPSS-QoL scores were determined at 1, 3, 6, 12 and 18 months post-treatment.</p> <p>Results</p> <p>Mean prostate volume at baseline, 82 ± 16 ml progressively decreased from month one coming to 49 ± 9,5 ml (p = 0,003) at month six. From this moment on, prostate volume slowly recovered, becoming identical to baseline at 18 months (73 ± 16 ml, p = 0.03). Albeit non significant, serum PSA showed a 25% decrease from baseline to month 6. The 11 patients resumed spontaneous voiding at month one. Mean Qmax was 11,3 ± 1,7 ml/sec and remained unchanged during the follow-up period. PVR ranged from 55 ± 17 to 82 ± 20 ml and IPSS score from10 to 12 points.</p> <p>Conclusion</p> <p>Intraprostatic BoNT/A injection is safe and can reduce prostate volume for a period of 18 months. During this time a marked symptomatic improvement can be maintained.</p

Distonias: aspectos terapêuticos

Diversas abordagens terapêuticas são utilizadas em pacientes com distonias. Sempre que possível, causas específicas devem ser identificadas e tratadas. As modalidades de tratamento sintomático podem ser agrupadas em três categorias: tratamento farmacológico, cirúrgico e injeções locais de toxina botulínica. Cada uma dessas modalidades apresenta algumas vantagens e limitações. Formas generalizadas, particularmente as de ocorrência na infância, podem se beneficiar com drogas anticolinérgicas ou, em alguns casos, com a levodopa ou outros agentes tais como antagonistas da dopamina, baclofeno e benzodiazepínicos. As formas focais não respondem adequadamente ao tratamento farmacológico sistêmico mas beneficiam-se significativamente com injeções de toxina botulínica nos grupos musculares acometidos. Cerca de 90% dos pacientes com blefarospasmo e 70% daqueles com distonia cervical apresentam resposta satisfatória a esse tipo de terapia. O tratamento cirúrgico tem sido utilizado em algumas formas de distonias generalizadas (lesões estereotáxicas), axiais (rizotomias) ou focais (miectomias e neurectomias) com resultados variáveis.Several approaches have been employed for the treatment of dystonias. Possible specific causes should be searched for and specific treatment should be instituted. Different types of symptomatic treatment are grouped according to the following categories: pharmacological systemic therapy, surgical therapy and botulinum toxin injections in the affected muscles. Each of these approaches has its advantages and limitations. Generalized dystonias should be treated with anticholinergic agents. In some cases, levodopa or other drugs such as dopamine antagonists, baclofen and benzodiazepines should be preferred. Focal dystonias respond dramatically to local injections of botulinum toxin. Over 90% of patients with blepharospasm and 70% of patients with cervical dystonia present a satisfactory response to this procedure. Surgical approaches have been utilized in some cases of generalized (stereotaxic lesions), axial (rhizotomies) and focal dystonias (myectomies and neurectomies) with variable results

The LabelHash algorithm for substructure matching

Background: There is an increasing number of proteins with known structure but unknown function. Determining their function would have a significant impact on understanding diseases and designing new therapeutics. However, experimental protein function determination is expensive and very time-consuming. Computational methods can facilitate function determination by identifying proteins that have high structural and chemical similarity. Results: We present LabelHash, a novel algorithm for matching substructural motifs to large collections of protein structures. The algorithm consists of two phases. In the first phase the proteins are preprocessed in a fashion that allows for instant lookup of partial matches to any motif. In the second phase, partial matches for a given motif are expanded to complete matches. The general applicability of the algorithm is demonstrated with three different case studies. First, we show that we can accurately identify members of the enolase superfamily with a single motif. Next, we demonstrate how LabelHash can complement SOIPPA, an algorithm for motif identification and pairwise substructure alignment. Finally, a large collection of Catalytic Site Atlas motifs is used to benchmark the performance of the algorithm. LabelHash runs very efficiently in parallel; matching a motif against all proteins in the 95 % sequence identity filtered non-redundant Protein Data Bank typically takes no more than a few minutes. The LabelHash algorithm is available through a web server and as a suite of standalone programs a

A Network Model of Local Field Potential Activity in Essential Tremor and the Impact of Deep Brain Stimulation

Essential tremor (ET), a movement disorder characterised by an uncontrollable shaking of the affected body part, is often professed to be the most common movement disorder, affecting up to one percent of adults over 40 years of age. The precise cause of ET is unknown, however pathological oscillations of a network of a number of brain regions are implicated in leading to the disorder. Deep brain stimulation (DBS) is a clinical therapy used to alleviate the symptoms of a number of movement disorders. DBS involves the surgical implantation of electrodes into specific nuclei in the brain. For ET the targeted region is the ventralis intermedius (Vim) nucleus of the thalamus. Though DBS is effective for treating ET, the mechanism through which the therapeutic effect is obtained is not understood. To elucidate the mechanism underlying the pathological network activity and the effect of DBS on such activity, we take a computational modelling approach combined with electrophysiological data. The pathological brain activity was recorded intra-operatively via implanted DBS electrodes, whilst simultaneously recording muscle activity of the affected limbs. We modelled the network hypothesised to underlie ET using the Wilson-Cowan approach. The modelled network exhibited oscillatory behaviour within the tremor frequency range, as did our electrophysiological data. By applying a DBS-like input we suppressed these oscillations. This study shows that the dynamics of the ET network support oscillations at the tremor frequency and the application of a DBS-like input disrupts this activity, which could be one mechanism underlying the therapeutic benefit