Dystonia: diagnosis and management.

Clinical practice in dystonia has greatly evolved in recent years; a synthetic review on patient management is provided here. Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures or both. A recent classification has innovated clinical practice and serves as guidance for clinical assessment: Axis I describes clinical features, whereas Axis II indicates etiology. Dystonia presents with different syndromic aggregations with varied somatic involvement and some common features. There are five recognizable physical signs of dystonia: two main signs (dystonic postures and movements) and three additional signs (gestes antagonistes or tricks, mirror dystonia and overflow dystonia). There is still no validation of diagnostic criteria for the different dystonia syndromes, and many cases with mild phenomenology remain undiagnosed. Patients with dystonia also present non-motor features that are variably combined with the movement disorder. The features of the most common inherited and acquired dystonia syndromes are reviewed here. There is clear evidence of genetic-environmental interaction in the determinism of dystonia. The diagnostic process is guided by clinical examination and based on specific laboratory examinations. Symptomatic treatments are available for dystonia: botulinum neurotoxin injections are the primary choice for most focal dystonia syndromes; deep brain stimulation is useful in some generalized and non-generalized syndromes. Additional treatment strategies are currently being assessed.

Tauroursodeoxycholic acid in the treatment of patients with amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: Tauroursodeoxycholic acid (TUDCA) is a hydrophilic bile acid that is produced in the liver and used for treatment of chronic cholestatic liver diseases. Experimental studies suggest that TUDCA may have cytoprotective and anti-apoptotic action, with potential neuroprotective activity. A proof of principle approach was adopted to provide preliminary data regarding the efficacy and tolerability of TUDCA in a series of patients with amyotrophic lateral sclerosis (ALS). METHODS: As a proof of principle, using a double-blind placebo controlled design, 34 ALS patients under treatment with riluzole who were randomized to placebo or TUDCA (1 g twice daily for 54 weeks) were evaluated after a lead-in period of 3 months. The patients were examined every 6 weeks. The primary outcome was the proportion of responders [those subjects with improvement of at least 15% in the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) slope during the treatment period compared to the lead-in phase]. Secondary outcomes included between-treatment comparison of ALSFRS-R at study end, comparison of the linear regression slopes for ALSFFRS-R mean scores and the occurrence of adverse events. RESULTS: Tauroursodeoxycholic acid was well tolerated; there were no between-group differences for adverse events. The proportion of responders was higher under TUDCA (87%) than under placebo (P = 0.021; 43%). At study end baseline-adjusted ALSFRS-R was significantly higher (P = 0.007) in TUDCA than in placebo groups. Comparison of the slopes of regression analysis showed slower progression in the TUDCA than in the placebo group (P < 0.01). CONCLUSIONS: This pilot study provides preliminary clinical data indicating that TUDCA is safe and may be effective in ALS.

Differential diagnosis of dystonia.

Dystonia is a movement disorder characterized by sustained muscle contractions causing twisting and repetitive movements and abnormal postures. Diagnosing dystonia may be difficult, because of variability of dystonia presentation, uncertain recognition of the specific clinical signs, wide etiological spectrum, and coexistence of other movement disorders. The major difficulties in the diagnostic assessment of primary and non-primary dystonia derive from its confusion with other movement disorders or with a psychogenic disorder. The clinical heterogeneity of dystonia and some examples of misdiagnosis are reviewed here. The movement disorders that can be most commonly taken for dystonia are tremor, Parkinson's disease, myoclonus, chorea, and tics. Given the occurrence of confounding factors, along with specific genetic and laboratory test, it is of great importance to apply a specific algorithm to recognize the clinical signs of dystonia.

Role of the calcarine cortex (V1) in perception of visual cues for saccades.

OBJECTIVE: To determine the initial level at which the pathways for cue perception, saccades and antisaccades diverge. METHODS: Two procedures: single pulse transcranial magnetic stimulation (sTMS) over posterior occiput and backward masking were used. A visual cue directed saccades to the left or right, either a pro-saccade (to the side of the cue but beyond it) or an antisaccade, i.e., contraversive saccade. No visual target was presented. RESULTS: Latencies of the two types of saccades did not differ. Focal sTMS applied unilaterally over V1 suppressed both perception of a cue flashed 80-90ms earlier contralaterally (but not ipsilaterally) and the appropriate saccade. Masking at a delay of 100ms abolished the appropriate saccade and cue perception. CONCLUSIONS: V1 is essential for the perception of a flashed cue and for executing appropriate pro- and contraversive saccades. Masking may occur beyond V1, where the pathways for perception and for saccades at least to the next visual processing level start separating. SIGNIFICANCE: VI is needed for rapid, accurate perceptual and motor responses to the crudest (left versus right) cues. It is unlikely that the "where" system can have a major direct input bypassing V1.

Epidemiology, clinical features and diagnosis of gastroenteropancreatic endocrine tumours.

Gastroenteropancreatic (GEP) neoplasms originate from any of the various cell types belonging to the neuroendocrine system. A general characteristic of GEP endocrine tumours is that the vast majority produce and secrete a multitude of peptide hormones and amines. Many patients with malignant metastasising tumours present clinical symptoms related to hormone hyperproduction. These include the so-called carcinoid syndrome, characterised by flushing, diarrhoea, wheezing and right heart disease, which is predominantly associated with the serotonin- and tachykinins-producing carcinoids of the midgut. Several types of syndrome associated with GEP endocrine tumors are caused by overproduction of a specific hormone. For instance, the well-known Zollinger-Ellison syndrome is gastrin-mediated. The so-called 'insulinoma syndrome' depends on excessive production of insulin and proinsulin, resulting in hypoglycemia. The 'glucagonoma syndrome' is characterised by necrolytic migratory erythema, diabetes and diarrhoea. The Verner-Morrison syndrome, which is brought about by high circulating levels of vasointestinal peptide (VIP). produces severe secretory diarrhoea. Finally the 'somatostatinoma syndrome' involves gallbladder dysfunction and gallstones, diarrhoea with or without steatorrhea, and impaired glucose tolerance. The biochemical diagnosis of endocrine digestive tumors is based on general and specific markers. The best general markers are chromogranin A (CgA) and pancreatic polypeptide (PP). Specific markers for endocrine tumors include insulin, gastrin, glucagon, vaso intestinal polypeptide (VIP), somatostatin and the primary cathabolic product of serotonin, 5-hydroxyndoleacetic acid (5-HIAA). Localisation procedures commonly applied, in the diagnosis of endocrine tumours include ultrasound (US), computed tomography (CT) and somatostatin receptor scintigraphy (SRS).

Changes in the excitability of the H-reflex in wrist flexors related to the prone or supine position of the forearm in man.

The effect of the forearm position, prone vs. supine, on the excitability of the H-reflex in flexor carpi radialis (FCR) muscle was tested in nine adult volunteers by comparing the recruitment profiles of the H and M waves. The H-reflex size, normalized to the maximal M response, was lower when the forearm was supine than when it was prone, with an average reduction of about 50% over most of the H-recruitment curve. In three wrist positions, intermediate between prone and supine, the amount of reflex attenuation was related to the prono-supination angle. Control experiments excluded that the changes in the H reflex excitability were due to displacements of the stimulating or recording electrodes.

Asymptomatic glucagonoma presenting with an isolated hepatic nodule.

A 37-year-old male patient, without any particular symptoms apart from moderate right upper quadrant postprandial pain, was found to have a liver mass identified as a glucagon-producing tumor. Plasma glucagon levels were slightly increased, whereas those of other gut peptides were within the normal range. Despite an extensive pre- and intraoperative diagnostic work-up, a presumed primary glucagonoma remained undetected. This unusual presentation with the absence of any symptoms typical of glucagonoma, as well as the presence of histopathological features characteristic of both benign and malignant forms of glucagonoma, make this case very peculiar. A clinically silent, apparently unrelated adenocarcinoma of the left colon was also found. The concomitant presence of a glucagonoma and a carcinoma of the large intestine has not been previously reported, and its significance remains unclear.

Changes in excitability of the flexor carpi radialis H-reflex following tactile stimulation of the index fingertip.

Adequate stimulation of cutaneous afferents from the fingertip evokes a short-latency inhibition followed by a long-lasting excitation in human flexor carpi radialis (FCR) motoneurones. Changes in excitability of flexor motoneurones were investigated in 11 subjects by means of the H-reflex conditioning technique. The index fingertip, immobilised on a flat table, was stimulated by a small probe mounted on an electromagnetic vibrator. Contact time and tactile perception threshold (PT) were monitored throughout the experiment. In all subjects, tactile stimulation of the skin covering the index pulp, with 10 ms long square pulses, at an intensity of 2-2.5 PT, produced an inhibition starting at a conditioning-test interval of 15 ms and lasting about 2 ms. This was followed by a powerful facilitation lasting more than 10 ms. Excitation appeared just at tactile threshold, whereas threshold for inhibition was about 2 PT. Similar effects were observed after mechanical stimulation of the skin covering the dorsal aspect of the index, close to the nail. Local anaesthesia of the finger pulp drastically reduced both the inhibition and the facilitation of FCR H-reflex. By contrast, electrical stimulation of the index digital nerves, by means of ring electrodes, was always ineffective in modifying the excitability of the FCR H-reflex. It is proposed that inhibition and excitation of FCR H-reflex are caused by activation of oligosynaptic pathways fed by cutaneous afferents; however, it cannot be excluded that joint receptors and primary endings of small hand muscles may contribute in part to the late excitation. The pathways described might play an essential role in modulation and control of exploratory movements and object manipulation, actions that need tactile information to regulate muscle force.