J. Valls-Solé

European federation of neurological societies/peripheral nerve society guideline on the use of skin biopsy in the diagnosis of small fiber neuropathy. report of a joint task force of the european fe-deration of neurological societies and the peripheral nerve society

Background:  Revision of the guidelines on the use of skin biopsy in the diagnosis of peripheral neuropathy, published in 2005, has become appropriate owing to publication of more relevant articles. Most of the new studies focused on small fiber neuropathy (SFN), a subtype of neuropathy for which the diagnosis was first developed through skin biopsy examination. This revision focuses on the use of this technique to diagnose SFN.

A practical guide to diagnostic transcranial magnetic stimulation: Report of an IFCN committee

Transcranial magnetic stimulation (TMS) is an established neurophysiological tool to examine the integrity of the fast-conducting corticomotor pathways in a wide range of diseases associated with motor dysfunction. This includes but is not limited to patients with multiple sclerosis, amyotrophic lateral sclerosis, stroke, movement disorders, disorders affecting the spinal cord, facial and other cranial nerves. These guidelines cover practical aspects of TMS in a clinical setting. We first discuss the technical and physiological aspects of TMS that are relevant for the diagnostic use of TMS. We then lay out the general principles that apply to a standardized clinical examination of the fast-conducting corticomotor pathways with single-pulse TMS. This is followed by a detailed description of how to examine corticomotor conduction to the hand, leg, trunk and facial muscles in patients. Additional sections cover safety issues, the triple stimulation technique, and neuropediatric aspects of TMS.

European Federation of Neurological Societies/Peripheral Nerve Society guideline on the use of skin biopsy in the diagnosis of small fiber neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society

Revision of the guidelines on the use of skin biopsy in the diagnosis of peripheral neuropathy, published in 2005, has become appropriate due to publication of more relevant papers. Most of the new studies focused on small fiber neuropathy (SFN), a subtype of neuropathy for which the diagnosis was first developed through skin biopsy examination. This revision focuses on the use of this technique to diagnose SFN. Task force members searched the Medline database from 2005, the year of the publication of the first EFNS guideline, to June 30th, 2009. All pertinent papers were rated according to the EFNS and PNS guidance. After a consensus meeting, the task force members created a manuscript that was subsequently revised by two experts (JML and JVS) in the field of peripheral neuropathy and clinical neurophysiology, who were not previously involved in the use of skin biopsy. Distal leg skin biopsy with quantification of the linear density of intraepidermal nerve fibers (IENF), using generally agreed upon counting rules, is a reliable and efficient technique to assess the diagnosis of SFN (level A recommendation). Normative reference values are available for bright‐field immunohistochemistry (level A recommendation) but not yet for confocal immunofluorescence or the blister technique. The morphometric analysis of IENF density, either performed with bright‐field or immunofluorescence microscopy, should always refer to normative values matched for age (level A recommendation). Newly established laboratories should undergo adequate training in a well established skin biopsy laboratory and provide their own stratified age and gender‐matched normative values, intra‐ and interobserver reliability, and interlaboratory agreement. Quality control of the procedure at all levels is mandatory (Good Practice Point). Procedures to quantify subepidermal nerve fibers and autonomic innervated structures, including erector pili muscles, and skin vessels are under development but need to be confirmed by further studies. Sweat gland innervation can be examined using an unbiased stereologic technique recently proposed (level B recommendation). A reduced IENF density is associated with the risk of developing neuropathic pain (level B recommendation), but it does not correlate with its intensity. Serial skin biopsies might be useful for detecting early changes of IENF density, which predict the progression of neuropathy, and to assess degeneration and regeneration of IENF (level C recommendation). However, further studies are warranted to confirm the potential usefulness of skin biopsy with measurement of IENF density as an outcome measure in clinical practice and research. Skin biopsy has not so far been useful for identifying the etiology of SFN. Finally, we emphasize that 3‐mm skin biopsy at the ankle is a safe procedure based on the experience of 10 laboratories reporting absence of serious side effects in approximately 35,000 biopsies and a mere 0.19% incidence of non‐serious side effects in about 15 years of practice (Good Practice Point).

Abnormalities of prepulse inhibition do not depend on blink reflex excitability: a study in Parkinson's disease and Huntington's disease.

OBJECTIVE Prepulse inhibition of the blink reflex is a robust phenomenon with an interesting physiology and a large potential for clinical applicability. In the study presented here we investigated whether the blink reflex inhibition by a prepulse (BRIP) is influenced by the blink reflex excitability recovery (BRER). METHODS The study was undertaken in 20 patients with Parkinsons disease (PD), 20 patients with Huntingtons disease (HD) and 20 healthy volunteers. BRER was determined by measuring the size of the response to a test supraorbital nerve stimulus as a percentage of the response to a conditioning stimulus at inter-stimuli intervals of 100-1000 ms. BRIP was determined as the percentage reduction induced in the response to a supraorbital nerve stimulus by either a low intensity auditory click or a weak third finger somatosensory stimulus, applied with a leading interval of 50-110 ms. RESULTS There was a negative correlation between the percentage BRER and the percentage BRIP (Pearsons correlation coefficient of -0.37). BRER was enhanced in 14 PD patients (70%) and 6 HD patients (30%), while it was depressed in 10 HD patients (50%). BRIP was significantly reduced in 15 PD patients (75%) and 16 HD patients (80%). No significant correlation was found between abnormally enhanced BRER and abnormally reduced BRIP in all patients as a group (chi(2)=2.4;P=0.11). A weak correlation was found in PD patients (P=0.019) and no correlation was observed in HD patients (P=0.8). CONCLUSIONS Our results indicate that an abnormally reduced BRIP was not always accompanied by an abnormally enhanced BRER in patients with HD. The two tests likely assess specific and distinct brainstem functions, and provide different types of information. While BRIP may be the result of a widespread integrative processing of sensory stimuli, BRER likely reflects the excitability of a chain of brainstem inter-neurons. SIGNIFICANCE BRER and BRIP provide independent information on the state of functionally separate circuits that converge on trigemino-facial brainstem inter-neurons.

Enhanced gain of blink reflex responses to ipsilateral supraorbital nerve afferent inputs in patients with facial nerve palsy

OBJECTIVES Patients with peripheral facial palsy (PFP) may present with transient hyperkinetic movement disorders in the side contralateral to the paralysis. One possible cause of such enhanced motor activity is sensitization of reflex responses to afferent inputs from the unprotected cornea. We hypothesized that if this sensitization occurs, the size of the orbicularis oculi (OOc) responses induced by afferents from the ophthalmic branch of the paralyzed side would be larger than those induced by afferents from the contralateral side. METHODS In 68 patients with complete PFP and in a group of 30 age-matched control subjects we recorded the response of the OOc muscle of one side to electrical stimulation of the supraorbital nerve of both sides, and calculated the ratio between R2c and R2 (R2c/R2). RESULTS The mean R2c/R2 ratio was significantly larger in patients than in control subjects (unpaired t test, P<0.05). Larger R2c than R2 responses were observed in 23.1% of control subjects and in 80.9% of patients (chi(2)=13.3, P<0.01). CONCLUSIONS Our results suggest that patients with PFP have an enhanced blink reflex gain to inputs from the paralyzed side compared to those of the non-paralyzed side. Sensitization of the blink reflex polysynaptic pathways to inputs carried by afferent fibers from the ophthalmic branch of the paralyzed side can play a role in inducing an abnormal facial motor behavior after PFP.

Usefulness of neurophysiologic techniques in stereotactic subthalamic nucleus stimulation for advanced Parkinson's disease.

OBJECTIVE The objectives of this study are to determine the impact of neurophysiologic guidance on subthalamic nucleus (STN) targeting and to assess its safety and effectiveness. METHODS We have compared the initial theoretic anatomic target (TAT) of the STN with the final microrecording guided coordinates in 15 consecutive patients with bilaterally implanted electrodes in the STN. The clinical results and adverse effects are also reported. All comparisons were done through a paired Students t test and Pearsons correlation test. RESULTS Neurophysiological guidance changed the target coordinates in 26 of the procedures. The mean correction applied to the TAT in order to place the electrode in its definite location was 0.4 mm (+/-0.8, range 0-3; P=0.03) in the medial-lateral axis, 1.6 mm (+/-1.2, range 0-5; P=0.01) in the anterior-posterior plane and 0.8 mm (+/-0.8, range 0-3; P=0.26) in the vertical axis. The mean number of microrecording tracks employed to localize each STN was 2.8+/-1.8 (range 1-8) tracks. After surgery, the total UPDRS motor score in the off medication condition improved by 65.9%; UPDRS-II scores were reduced by 71.8% and Schwab and England scores improved by 45.3%. No intraoperative hemorrhages occurred in this series. CONCLUSIONS Neurophysiological guidance is a safe and useful tool in order to improve and confirm target localization. The correction applied in the target resulted in a significant clinical improvement 6 months after surgery.

The effect of a prepulse stimulus on the EMG rebound following the cutaneous silent period

The cutaneous silent period (CSP) is a spinal inhibitory reflex mediated by Aδ fibres. The postinhibitory rebound of electromyographic (EMG) activity following the CSP has been mainly attributed to resynchronization of motoneurons, but the possibility of startle reflex activity contributing to the EMG burst has also been suggested. Several types of reflexes may be suppressed by a preceding weak stimulus – a phenomenon called prepulse inhibition (PPI). Our aim was to study whether PPI would diminish the EMG rebound, thereby providing further evidence for excitatory reflex activity contained within the postinhibitory EMG rebound following the CSP. Ten healthy subjects underwent CSP testing following noxious digit II stimulation in two conditions, with and without a prepulse applied to digit III. Rectified surface EMG recordings were obtained from right orbicularis oculi, sternocleidomastoid and thenar muscles of the dominant hand during thumb abduction with 25% of maximum force. The area of the EMG rebound and the EMG reflex responses in orbicularis oculi and sternocleidomastoid were significantly smaller in recordings where a prepulse stimulus was applied 100 ms before the stimulus as compared to control responses without prepulse. CSP onset and end latency, CSP duration, and the degree of EMG suppression were not influenced. Prepulses significantly reduced subjective discomfort as based on visual analog scale scores. Inhibition of the EMG rebound by prepulse stimulation supports the hypothesis that the excitatory EMG activity following the CSP contains not only resynchronization of motoneuronal firing, but also an excitatory reflex component. The most probable type of reflex seems to be a somatosensory startle reflex, a defence reaction which is generated in structures located in the caudal brainstem following an unexpected intense stimulus. Reduction of the discomfort associated with high‐intensity electrical fingertip stimulation by a prepulse without affecting CSP parameters underlines the utility of PPI in the context of CSP testing.

Changes in the sympathetic skin response after thoracoscopic sympathectomy in patients with primary palmar hyperhidrosis

OBJECTIVE To investigate whether thoracic sympathectomy induced any change in the pattern of abnormalities or in the waveform of the sudomotor skin response (SSR) in patients with primary palmar hyperhidrosis (PPH). METHODS We recorded the SSR to median nerve electrical stimuli before and after bilateral thoracoscopic sympathectomy in 27 patients with PPH. We analyzed the changes in amplitude, type of waveform and pattern of abnormality. RESULTS All patients reported symptomatic improvement. The amplitude of the SSR decreased significantly in patients examined within 1 year after surgery, but was not different in patients examined after 1 year. The number of abnormally enhanced responses reduced after surgery, but there was no significant change in the number of patients with enhanced excitability recovery or with double-peak responses to single stimuli. There was a significant increase in the number of SSRs with a predominantly negative waveform after surgery. CONCLUSIONS The persistence of SSR abnormalities after surgery suggests that the central nervous system dysfunction is not modified by sympathectomy. The change of the waveform to predominantly negative type after surgery could be the consequence of the decrease in the production of sweating. SIGNIFICANCE Our results show the effects of sympathectomy on the SSR and on its abnormal patterns in patients with PPH.

The StartReact effect in tasks requiring end-point accuracy

OBJECTIVE Fast and accurate movements are often performed in response to a sensory signal. In reaction time tasks, execution of open loop movements is speeded up when a startling auditory stimulus (SAS) is applied together with the imperative signal (IS). In this study, we examined the effects of a SAS on the performance of a task that demands accuracy. METHODS Nine subjects were asked to move a monitored pen to a target point located in a table at a fixed angular distance of 30 degrees from a start point. The target was a spot of three possible diameters: 5, 10, and 20mm. Finger force for pen holding, pen tip pressure against the table and kinematic variables of the forearm movement were measured for three conditions: control, SAS delivered at IS (SAS-IS trials) and SAS delivered during movement execution (SAS-MOV trials). RESULTS Two movement phases could be identified in the movement trajectory and force profile. The first phase, ballistic, was significantly shortened in SAS-MOV trials, with earlier and larger peak velocity and peak force with respect to control trials. The second phase, slow approach to target, was longer in SAS-IS trials but not in SAS-MOV trials. Accuracy was maintained throughout all conditions and stimulation modes. CONCLUSIONS A SAS speeds up only the first (ballistic) part of the movement in an accuracy task. Slower target approach compensates for the accelerated initial movement. No changes in the last part of the movement are seen when a SAS is delivered after movement onset. SIGNIFICANCE The StartReact effect is restricted to the onset of a complex movement, when muscles are activated in a ballistic mode, without feedback.

P05. Startle reactions to somatosensory inputs. Different response pattern to stimuli of upper and lower limbs

and smooth pursuit. Peak saccade velocity (main sequence) and saccadic gain were calculated. In addition, video recordings were performed to evaluate OMA. Results: Oculomotor abnormalities ranged from a complete ophthalmoplegia to dysmetric saccades. Slowing of saccades was found in six out of the seven patients. Five out seven patients showed OMA. Interestingly, unlike her sister one of girl the monozygotic twin did not show any eye movement abnormality. Smooth pursuit was normal except for the patient with complete ophthalmoplegia. Conclusions: All observed eye movement abnormalities in the patient group with type 3 Gaucher disease are indicative for brainstem pathology. Particularly, the neural circuitry consisting of burst neurons and pause cells in the reticular formation is malfunctioning. Phenotype varied, even between monozygotic twins.