Electro-clinical presentation of hereditary transthyretin related amyloidosis when presenting as a polyneuropathy of unknown origin in northern France.

INTRODUCTION: Hereditary transthyretin related amyloidosis (h-ATTR) classically presents as a small fiber neuropathy with positive family history, but can also be revealed by various other types of peripheral neuropathy. OBJECTIVE: To describe the initial electro-clinical presentation of patients from in a single region (northern France) of h-ATTR when it presents as a polyneuropathy of unknown origin. METHOD: We reviewed the records of patients referred to two neuromuscular centers from northern France with a peripheral neuropathy of unknown origin who were subsequently diagnosed with h-ATTR. RESULTS: Among 26 h-ATTR patients (10 Val30Met, 16 Ser77Tyr), only 14 patients had a suspicious family history (53.8%). The electro-clinical presentation was mostly a large-fiber sensory motor polyneuropathy (92.3%), which could be symmetric or not, length-dependent or not, or associated with nerve entrapment or not. Demyelinating signs were observed in 17 patients (70.8%), among whom nine fulfilled the criteria for a definite diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (37.5%). CONCLUSION: h-ATTR may have a wide spectrum of clinical profiles, and should be considered in the screening of polyneuropathies of unknown origin.

Impact of implementing an online interactive educational tool for future HIV "cure" research in an HIV clinic waiting room in Cape Town, South Africa.

Access to antiretroviral treatment (ART) in South Africa is suboptimal and erratic. For those on treatment, compliance remains a significant challenge. Interruptions to ART have negative implications for the individual and the epidemic. ART is therefore not a sustainable solution and there is an urgent need for a cure. As HIV cure research expands globally, the need to engage community members about cure is becoming a priority. It is vital that potential trial participants understand basic HIV cure research concepts. An online interactive educational tool was co-created with HIV stakeholders to engage and inform HIV research trial participants. The study was conducted with patients at the FAMCRU HIV clinic at Tygerberg Hospital in Cape Town, South Africa. The educational tool comprises two modules that provide information on HIV prevention, treatment and cure research. Participants completed a questionnaire before and after interacting with the programme. There was a significant increase in knowledge scores of participants demonstrated after using the tool. The interactive tool was successful in increasing participants' knowledge of HIV prevention, treatment and cure research.

Lower-limb neurologic deficit after vaginal delivery: a prospective observational study.

BACKGROUND: Lower limb neurologic deficit after vaginal delivery remains poorly understood. The objective of this study was to describe the incidence, characteristics and prognosis associated with nerve injury occurring to women during vaginal delivery. METHODS: A single-center observational study of women who complained about a lower limb neurologic deficit that appeared immediately after vaginal delivery. The follow-up period was up to four years. RESULTS: Among the 10 569 women with a singleton vaginal delivery during the 30-month study period, 31 (0.3%) reported a neurologic deficit. Most women were nulliparous (71%) and the mean duration of the second stage of labor was 94 min [range 13-224 min]. In two-thirds of cases, delivery required instrumental assistance. Most neurologic deficits were sensory (67.7%) and primarily involved femoral nerve territory (83.9%). Most women recovered within six weeks (69.2%). In one case (a sensory deficit of the entire right leg), recovery only occurred after 3.5 years. CONCLUSION: Neurologic deficit was identified in 0.3% of our vaginal delivery population. Recovery from neurologic deficit may take many weeks and may occasionally be disabling.

Outcomes of outpatient ureteral stenting without fluoroscopy at Groote Schuur Hospital, Cape Town, South Africa.

BACKGROUND: Ureteral stenting is generally a theatre-based procedure that requires a multidisciplinary team and on-table imaging. Limited hospital bed numbers and theatre time in our centre in Cape Town, South Africa, have led us to explore an alternative approach. OBJECTIVES: To see whether outpatient insertion of ureteric stents under local anaesthesia without fluoroscopy was a possible and acceptable alternative to theatre-based ureteral stenting. METHODS: Ureteral stenting (double-J stents and ureteric catheters) was performed with flexible cystoscopy under local anaesthesia and chemoprophylaxis, but without fluoroscopic guidance, in an outpatient setting. Every patient had an abdominal radiograph and an ultrasound scan of the kidney after the procedure to confirm stent position. RESULTS: Three hundred and sixteen procedures (276 double-J stents and 40 ureteric catheters) were performed in 161 men and 155 women. The overall success rate for the procedures was 85.4%, independent of gender (p=0.87), age (p=0.13), type of device inserted (p=0.81) or unilateral/bilateral nature of the procedure (p=1.0). Procedures with a successful outcome were performed in a significantly (p<0.0001) shorter median time (10 minutes (interquartile range (IQR) 5 - 15)) than failed procedures (20 minutes (IQR 10 - 30)). Patients with a pain score of >5 experienced a significantly (p=0.02) greater proportion of failure (27.3%) than patients with a pain score of ≤5 (12.5%). Difficulties were encountered in 23.7% of procedures, with a significantly higher proportion being registered in failed interventions compared with successful ones (82.6% v. 13.7%; p<0.0001). CONCLUSIONS: The procedure was easily mastered and technically simple, and represents savings in cost, time and human resources in our setting.

Movement preparation and cortical processing of afferent inputs in cortical tremor: an event-related (de)synchronization (ERD/ERS) study.

OBJECTIVE: We sought to characterize cortical activity related to motor control in patients presenting with isolated cortical tremor, in order to determine whether or not myoclonus-related impairments are a source of event-related desynchronization/synchronization (ERD/ERS) disruption. METHODS: Nine patients presenting with isolated cortical tremor were compared with controls. Mu and beta ERD/ERS were computed over the scalp and brain surfaces using 128-channel electroencephalographic (EEG) recording during voluntary and passive finger extensions. We recorded somatosensory-evoked potentials following median nerve stimulation and performed myoclonic jerk-locked back-averaging of EEG activity. RESULTS: Back-averaging revealed a cortical premyoclonic spike in all patients. Five of the nine patients had exaggerated SEPs. The amplitude of mu ERD was greater in patients. Beta ERD/ERS did not differ from that seen in controls. Localizations of mu and beta ERD/ERS did not differ from controls and were identified in pre- and post-central sensorimotor cortical areas. CONCLUSIONS: The present results suggest a hyperexcitability of the cortico-subcortical loops responsible for movement preparation and execution. Post-movement inhibition related to cortical processing of afferent input is unaffected in isolated cortical myoclonus. SIGNIFICANCE: Intracortical abnormalities can differ in patients suffering from cortical myoclonus, according to whether or not the individuals have associated epileptic symptoms.

CEPHEUS SA: a South African survey on the undertreatment of hypercholesterolaemia.

AIM: The aim of the CEntralised Pan-South African survey on tHE Under-treatment of hypercholeSterolaemia (CEPHEUS SA) was to evaluate the current use and efficacy of lipidlowering drugs (LLDs), and to identify possible patient and physician characteristics associated with failure, if any, to achieve low-density lipoprotein cholesterol (LDL-C) targets. METHODS: The survey was conducted in 69 study centres in South Africa and recruited consecutive consenting patients who had been prescribed LLDs for at least three months. One visit was scheduled for data collection, including fasting plasma lipid and glucose levels. Physicians and patients completed questionnaires regarding their knowledge, awareness and perceptions of hypercholesterolaemia and the treatment thereof. RESULTS: Of the 3 001 patients recruited, 2 996 were included in the final analyses. The mean age was 59.4 years, and 47.5% were female. Only 60.5 and 52.3% of patients on LLDs for at least three months achieved the LDL-C target recommended by the NCEP ATP III/2004 updated NCEP ATP III and the Fourth JETF/South African guidelines, respectively. Being male, older than 40 years, falling into the lower-risk categories, compliance with the medication regimen, and patient knowledge that the LDL-C goal had been reached, were associated with the highest probability of attaining LDL-C goals. CONCLUSION: The results of this survey highlight the sub-optimal lipid control achieved in many South African patients taking lipid-lowering therapy.

Afferent-induced facilitation of primary motor cortex excitability in the region controlling hand muscles in humans.

Sensory inputs from cutaneous and limb receptors are known to influence motor cortex network excitability. Although most recent studies have focused on the inhibitory influences of afferent inputs on arm motor responses evoked by transcranial magnetic stimulation (TMS), facilitatory effects are rarely considered. In the present work, we sought to establish how proprioceptive sensory inputs modulate the excitability of the primary motor cortex region controlling certain hand and wrist muscles. Suprathreshold TMS pulses were preceded either by median nerve stimulation (MNS) or index finger stimulation with interstimulus intervals (ISIs) ranging from 20 to 200 ms (with particular focus on 40-80 ms). Motor-evoked potentials recorded in the abductor pollicis brevis (APB), first dorsalis interosseus and extensor carpi radialis muscles were strongly facilitated (by up to 150%) by MNS with ISIs of around 60 ms, whereas digit stimulation had only a weak effect. When MNS was delivered at the interval that evoked the optimal facilitatory effect, the H-reflex amplitude remained unchanged and APB motor responses evoked with transcranial electric stimulation were not increased as compared with TMS. Afferent-induced facilitation and short-latency intracortical inhibition (SICI) and intracortical facilitation (ICF) mechanisms are likely to interact in cortical circuits, as suggested by the strong facilitation observed when MNS was delivered concurrently with ICF and the reduction of SICI following MNS. We conclude that afferent-induced facilitation is a mechanism which probably involves muscle spindle afferents and should be considered when studying sensorimotor integration mechanisms in healthy and disease situations.

[Myoclonus and epilepsy: diagnosis and pathophysiology]. / Myoclonies et myoclonies épileptiques: orientation diagnostique et connaissances physiopathologiques.

Myoclonus presents as a sudden brief involuntary jerk triggered by the central nervous system. Electromyographic studies enable determining whether the jerk is caused by a muscular contraction, i.e. positive myoclonus, or by an interruption of muscular activity, i.e. negative myoclonus. Many classifications have been proposed, reflecting our lack of understanding about myoclonus. Myoclonus is a symptom and should never be considered as a diagnosis. Clinical history and physical examination are the basis to diagnosis. Clinical neurophysiology testing can reveal a neuroanatomical localization and certain patterns have some etiological specificity. Etiological hypotheses can be put forward on the basis of clinical and neurophysiological data. The cortex is the most commonly identified source of myoclonus, but the subcortical area and spinal area can also be involved. Myoclonus is considered epileptic when it is combined with an epileptiform discharge on the EEG. The International Classification of Epileptic Syndromes should be applied in this situation. Myoclonic epilepsies are a collection of syndromes in which myoclonic seizures are a prominent feature. Myoclonus can occur as one among several seizure components, as the only manifestation of seizure, or as one of multiple seizure types within an epileptic syndrome. Neurophysiological studies are needed to investigate the pathophysiological mechanisms of the myoclonus. Electrophysiological studies report that myoclonic seizures are produced through a cortical generator via a polysynaptic mechanism acting on muscles. Apparently, the epileptiform discharges stimulate the motor cortex resulting in myoclonus jerk. Despite recent progress, advances are still needed to achieve a better understanding of the pathophysiological mechanisms involved in myoclonus. In myoclonic epileptic syndromes, more useful information can probably be obtained from studies grouping several patients with a same epileptic syndrome than from single case reports.

The effects of low- and high-frequency repetitive TMS on the input/output properties of the human corticospinal pathway.

The objective of this study was to characterize the effects of various parameters (notably the frequency and intensity) of repetitive transcranial magnetic stimulation (rTMS) applied over the primary motor (M1) and premotor (PMC) cortices on the excitability of the first dorsalis interosseus (FDI) corticospinal pathway. To this end, we applied a comprehensive input-output analysis after fitting the experimental results to a sigmoidal function. Twenty-six healthy subjects participated in the experiments. Repetitive TMS was applied either over M1 or PMC at 1 Hz (LF) for 30 min (1,800 pulses) or at 20 Hz (HF) for 20 min (1,600 pulses). In the HF condition, the TMS intensity was set to 90% (HF(90)) of the FDI's resting motor threshold (RMT). In the LF condition, the TMS intensity was set to either 90% (LF(90)) or 115% (LF(115)) of the RMT. The FDI input/output (I/O) curve was measured on both sides of the body before rTMS (the Pre session) and then during two Post sessions. For each subject, the I/O curves (i.e., the integral of the FDI motor-evoked potential (MEP) vs. stimulus intensity) were fitted using a Boltzmann sigmoidal function. The graph's maximum slope, S (50) and plateau value were then compared between Pre and Post sessions. LF(115) over M1 increased the slope of the FDI I/O curve but did not change the S (50) and plateau value. This also suggested an increase in the RMT. HF(90) led to a more complex effect, with an increase in the slope and a decrease in the S (50) and plateau value. We did not see a cross effect on the homologous FDI corticospinal pathway, and only PMC LF(90) had an effect on ipsilateral corticospinal excitability. Our results suggest that rTMS may exert a more complex influence on cortical network excitability than is usually reported (i.e. simple inhibitory or facilitatory effects). Analysis of the fitted stimulus response curve indicates a dichotomous influence of both low- and high-frequency rTMS on M1 cortical excitability; this may reflect intermingled effects on excitatory and inhibitory cortical networks.

Anticipatory postural adjustments associated with arm movement in Parkinson's disease: a biomechanical analysis.

OBJECTIVE: To study anticipatory postural adjustments (APAs) in Parkinson's disease (PD) via a biomechanical analysis, including vertical torque (Tz). METHODS: Ten patients with PD (in the "off-drug" condition) and 10 age matched controls were included. While standing on a force platform, the subject performed a right shoulder flexion in order to grasp a handle in front of him/her, under three conditions (all at maximal velocity): movement triggered by a sound signal and loaded/non-loaded, self-paced movement. The anteroposterior coordinates of the centre of pressure (COP) and Tz were calculated. RESULTS: A group effect was observed for Tz and COP in patients with PD (compared with controls): the maximal velocity peak appeared later and the amplitude of the COP backward displacement and the area of the positive phase of Tz were lower, whereas the duration of the positive phase of Tz was greater. Interaction analysis showed that the area of Tz was especially affected in the triggered condition and the loaded, self-paced condition. The onset of the COP backward displacement was delayed in the triggered condition. CONCLUSION: Our biomechanical analysis revealed that patients with PD do indeed perform APAs prior to unilateral arm movement, although there were some abnormalities. The reduced APA magnitude appears to correspond to a strategy for not endangering postural balance.

[Neurophysiology of corticobasal degeneration]. / Neurophysiologie de la dégénérescence corticobasale.

INTRODUCTION: Corticobasal degeneration (CBD) is a neurodegenerative disorder of mid- to late-adult life. From a clinical standpoint, CBD is characterized by (i) an insidious onset and a slowly progressing, unilateral, levodopa-unresponsive parkinsonian syndrome with dystonia or myoclonus and (ii) cerebral features such as apraxia, alien limb phenomena and cortical sensory loss. Decisive clinical diagnostic criteria are not available and thus a neuropathological study remains essential for accurate CBD diagnosis. Consequently, additional non-clinical criteria must be identified in order to improve diagnosis while patients are still alive. BACKGROUND: Electrophysiological exploration can yield functional information on a number of brain structures (both cortical and sub-cortical) involved in CBD. The disorder features a specific cortical (frontoparietal) alteration which could help with differential diagnoses for other extrapyramidal syndromes. Hence, exploration of a patient's myoclonus can provide some specific arguments for CBD. Indeed, myoclonus displays a number of clinical and electromyographical characteristics which are consistent with a cortical origin (a shorter latency of the cortical C response, for example). However, some typical cortical features are missing (giant somesthesic evoked potentials, and cortical potentials preceding myoclonus in jerk-locked back-averaging studies). Some authors explain these abnormalities in terms of a sub-cortical origin for the myoclonus. The frontoparietal alteration in CBD has also been explored in studies of oculomotor movement. Indeed, asymmetric lengthening of the lateral ocular saccade latency argues more in favour of CBD than progressive supranuclear palsy. Moreover, cognitive function is also compromised in the early stages of CBD, although it is sometimes difficult to distinguish between CBD, PSP and frontotemporal dementia. Studying cognitive potentials enables one to confirm subcorticofrontal abnormalities and to dissociate CBD patterns from PSP patterns. Other electrophysiological tests (such as the exploration of dysautonomia, the palmomental reflex and the blink reflex) produce results which overlap with those seen in extrapyramidal syndromes and synucleinopathies (polysomnography), prompting discussion of the physiopathological mechanisms of these various diseases. CONCLUSION: Electrophysiological exploration is of value for diagnosing CBD in general and for studying specific, frontoparietal dysfunctions in particular. These techniques could also significantly contribute to our understanding of the physiopathology of CBD.

Motor representation areas in epileptic patients with focal motor seizures: a TMS study.

PURPOSE: This study used TMS mapping to investigate the motor representation of the abductor pollicis brevis (APB) muscles in a group of patients with focal epilepsy originating in central or pre-central region. METHODS: Eight epileptic patients and eight control subjects participated in the study. The coil was moved in 1.5-cm steps along a grid drawn on the subject's skull over the motor cortex of both hemispheres. At each site, six APB motor responses (evoked by TMS at 1.2 times the resting motor threshold) were recorded and averaged. The peak-to-peak amplitude was measured and plotted against the mediolateral and anteroposterior coil positions. The area of each APB muscle representation was measured and the position of the optimal point was calculated. RESULTS: The resting motor threshold was increased bilaterally in epileptic patients. The maps were distorted in most patients (but not in control subjects), as evidenced by an off-centre optimal point. Interhemispheric differences in APB map areas were greater in patients than in control subjects. However, whether these increases in map area were on the epileptic side or on healthy side depended on the given subject. CONCLUSIONS: The changes in APB representation observed in epileptic patients demonstrate that reorganization occurs within the motor cortex. The heterogeneity of the present results is probably related to different locations of the epileptogenic and/or lesional areas and to a variety of compensatory phenomena that may occur, notably with respect to the disease duration.

Low frequency repetitive transcranial magnetic stimulation over premotor cortex can improve cortical tremor.

OBJECTIVE: To examine the effects of a 30 min, 1 Hz subthreshold rTMS in a case of cortical tremor which is caused by hyperexcitability of sensorimotor cortex. METHODS: Stimulation was applied over primary and, in a second time, over premotor cortex (M1 and PMC, respectively). Tremor was monitored by accelerometers placed on the index fingers of hands outstretched, before and several times after rTMS. Each rTMS session consisted of 1800 pulses delivered at 1 Hz with an intensity of 90% of resting motor threshold. RESULTS: PMC but not M1 stimulation led to a decrease of the postural tremor (90% decrease of acceleration total spectral power). This functional benefit was associated to normalization of electrophysiologic parameters (short-interval intracortical inhibition and cortical silent period duration). Moreover, when stimulating PMC during two daily sessions, improvement of the tremor was longer than one day stimulation and this benefit was associated with functional improvement. CONCLUSIONS: This study shows that 1 Hz rTMS over premotor cortex can improve cortical tremor. SIGNIFICANCE: These results raise the interest of the motor cortical stimulation as a possible therapeutic target for treatment of action tremor.

The effect of repetitive transcranial magnetic stimulation on dystonia: a clinical and pathophysiological approach.

Dystonia is characterized by sustained muscle contraction, which frequently causes repetitive, twisting movements or abnormal posture. The precise pathophysiological mechanisms of dystonia are still unknown. Several studies did demonstrate that, although motor cortex hyperexcitability appears to be responsible for abnormal co-contraction and overflow to adjacent muscles, plasticity mechanisms and integrative sensorimotor processing are also likely to be involved in this condition. Current dystonia treatments are based on oral medication, injection of botulinum toxin and, in a low proportion of cases, bi-pallidal deep brain stimulation. However, treatment outcome is generally disappointing. A few researchers have reported the application of repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex or the premotor cortex, with the goal of decreasing motor cortex hyperexcitability. This article reviews all studies using this technique in dystonia and discusses rTMS therapeutic impact and its possible mechanisms of action in this indication. Currently, the premotor cortex seems to be the best target for rTMS in dystonia. Rather than merely reducing the hyperexcitability of the primary motor cortex, this technique's clinical benefit seems to result from modifications in plasticity and restoration of sensorimotor integration. The corollary technique for chronic rTMS is electrical cortical stimulation. Even though this new therapeutic tool may have therapeutic promise, more studies are required to confirm it. In particular, we need to broaden our knowledge of rTMS impact on the various forms of dystonia and to optimize target localization.

Oscillatory cortical activity related to voluntary muscle relaxation: influence of normal aging.

OBJECTIVE: In this study we aimed to investigate if there are age-related differences in cortical oscillatory activity induced by self-paced muscular pure relaxation in comparison with muscle contraction as reference movement. METHODS: Event-related (de)synchronization (ERD/ERS) have been recorded related to voluntary muscle contraction and relaxation in 10 young and 10 elderly right-handed healthy subjects. The muscle relaxation task consisted in a voluntary relaxation of maintained wrist extension without any overt, associated muscle contraction. The muscle contraction task corresponded to a self-initiated brief wrist extension. RESULTS: In elderly subjects compared to young ones, mu and beta ERD preceding muscular relaxation was more widespread, beginning significantly earlier over contralateral frontocentral and parietocentral regions (p<0.05) as well as over ipsilateral regions (p<0.05). The beta synchronization was significantly attenuated (p<0.05). CONCLUSIONS: These results suggest an alteration of inhibitory motor systems and an altered post-movement somesthetic inputs processing with normal aging. These alterations were accompanied by compensatory mechanisms. SIGNIFICANCE: These age-related alterations during different phases of muscle relaxation could participate to explain global sensorimotor slowing observed with normal aging.

Predominance of the contralateral movement-related activity in the subthalamo-cortical loop.

OBJECTIVE: Abnormal low- and high-frequency oscillatory activities have been linked to abnormal movement control in Parkinson's disease. We aimed to study how low- and high-frequency oscillatory activities are modulated by movement in the contralateral and ipsilateral subcorticocortical loops. METHODS: We studied mu, beta and gamma rhythm event-related desynchronisation (ERD) and synchronisation (ERS) recorded from electrode contacts in the subthalamic nucleus (STN) areas and over the primary sensorimotor (PSM) cortex. RESULTS: Mu and beta ERD/ERS patterns were very similar when comparing PSM cortex and STN areas and very different when comparing contralateral and ipsilateral structures. Beta rhythm ERS was more predominant over contralateral structures than over ipsilateral ones. Gamma rhythm ERS was only recorded from the contralateral STN area (particularly following administration of L-Dopa). For all patients, the best bipolar derivations - as defined by the earliest mu and beta ERD and the strongest beta and gamma ERS - always included the STN electrode contacts that produced the best clinical results. CONCLUSIONS: Movement-related activity is involved in the movement preparation in the contralateral subthalamo-cortical loop and in the movement execution in the bilateral subthalamo-cortical loops. SIGNIFICANCE: Contralateral beta rhythm ERD seemed to be related to bradykinesia of the limb performing the movement.

Relationship between event-related beta synchronization and afferent inputs: analysis of finger movement and peripheral nerve stimulations.

OBJECTIVE: We compared beta synchronization associated with voluntary finger movement with beta synchronization produced by sensory stimulation, in order to better understand the relationship between event-related beta synchronization (ERS) and the different afferent inputs. METHODS: Twenty-four subjects performed an index finger extension. They also received three types of electrical stimulation (cutaneous stimulation of the index finger, single and repetitive stimulation of the median nerve). An EEG was recorded using 38 scalp electrodes. Beta ERS was analyzed with respect to movement offset and the stimulus (or the last stimulus in the series, for repetitive stimulation). RESULTS: Median nerve stimulation and finger extension induced more intense beta ERS than cutaneous stimulation. The magnitude of beta ERS induced by movement or by single median nerve stimulation were not different but post movement beta synchronization duration was longer than beta ERS induced by single median nerve stimulation and cutaneous stimulation. CONCLUSIONS: This study demonstrates that beta ERS depends on the type and quantity of the afferent input. SIGNIFICANCE: This work reinforces the hypothesis of a relationship between beta ERS and processing of afferent inputs.