Comparison of virtual reality rehabilitation and conventional rehabilitation in Parkinson's disease: a randomised controlled trial.

OBJECTIVE: To compare a 6-week virtual reality (VR) rehabilitation programme with a conventional rehabilitation programme in patients with Parkinson's disease. DESIGN: Prospective, single-blinded, randomised controlled trial. SETTING: Outpatients. PARTICIPANTS: Fifty-one patients with Parkinson's disease were assigned at random to a VR rehabilitation programme or a conventional rehabilitation programme. INTERVENTIONS: Both programmes ran for 6 consecutive weeks, with a 40-minute session three times per week. MAIN OUTCOME MEASURES: The Balance Berg Scale (BBS) was used to measure balance. Secondary outcome measures were: Dynamic Gait Index (DGI) to evaluate ability to adapt gait to complex walking tasks; Disabilities of the Arm, Shoulder and Hand (DASH) scale to measure performance of the upper limb; and Short Form 36 (SF-36) to evaluate quality of life. RESULTS: The VR rehabilitation programme led to an increase in BBS score {45.6 [standard deviation (SD) 7.9] vs 49.2 (SD 8.1), mean difference 3.6, 95% confidence interval (CI) 1.3 to 5.9; P=0.003}, DGI score [18.7 (SD 4.7) vs 20.2 (SD 4.2), mean difference 1.6, 95% CI 0.6 to 2.5; P=0.003] and SF-36 mental composite score [37.7 (SD 11.4) vs 43.5 (SD 9.2), mean difference 5.8, 95% CI 0.4 to 11.3; P=0.037], and a decrease in DASH scale score [29.6 (SD 17.5) vs 21.6 (SD 15.1), mean difference -7.9, 95% CI -13.7 to -2.2; P=0.009]. In contrast, the conventional rehabilitation programme only led to a decrease in DASH scale score [30.3 (SD 18.1) vs 25.1 (SD 15.8), mean difference -5.2, 95% CI -8.8 to -1.5; P=0.007]. CONCLUSION: These findings suggest that rehabilitation is useful in Parkinson's disease, and the VR rehabilitation programme was more effective in determining overall improvement than the conventional rehabilitation programme. CLINICAL TRIAL REGISTRATION NUMBER: NCT02807740.

Treadmill training in patients affected by Charcot-Marie-Tooth neuropathy: results of a multicenter, prospective, randomized, single-blind, controlled study.

BACKGROUND AND PURPOSE: Muscle-strengthening, stretching or proprioceptive treatments may slow symptom progression in Charcot-Marie-Tooth (CMT) neuropathy. The aim of the study was to evaluate safety and efficacy of treadmill training in CMT1A. METHODS: We planned a multicenter, prospective, randomized, single-blind, controlled study. We recruited 53 outpatients affected by CMT1A and randomized them into two treatment groups: one underwent stretching and proprioceptive exercise, whereas the other was additionally treated with treadmill training (TreSPE). Primary outcome measures (OMs) were the walking evaluations and secondary OM was the balance assessment. All participants were assessed at baseline and after 3 and 6 months of treatment. RESULTS: Most patients showed an improvement in at least one OM after 3 months [42/47 (89.4%)] and 6 months [38/40 (95%)] of treatment. No adverse events were reported in either group. CONCLUSIONS: The most important finding was that both stretching and proprioceptive exercise and treadmill training had an objective benefit on patients affected by CMT disease, without causing overwork weakness. We had a low rate of drop out and did not find deterioration in motor performance. Our results also confirm that applying evidence-based medicine methods to rehabilitative research is the correct way to test the efficacy of a treatment.

Cognitive reserve as a useful variable to address robotic or conventional upper limb rehabilitation treatment after stroke: a multicentre study of the Fondazione Don Carlo Gnocchi.

BACKGROUND AND PURPOSE: Rehabilitation plays a central role in stroke recovery. Besides conventional therapy, technological treatments have become available. The effectiveness and appropriateness of technological rehabilitation are not yet well defined; hence, research focused on different variables impacting recovery is needed. Results from the literature identified cognitive reserve (CR) as a variable impacting on the cognitive outcome. In this paper, the aim was to evaluate whether CR influences the motor outcome in patients after stroke treated with conventional or robotic therapy and whether it may influence one treatment rather than another. METHODS: Seventy-five stroke patients were enrolled in five Italian neurological rehabilitation centres. Patients were assigned either to a robotic group, rehabilitation by means of robotic devices, or to a conventional group, where a traditional approach was used. Patients were evaluated at baseline and after rehabilitation treatment of 6 weeks through the Action Research Arm Test (ARAT), the Motricity Index (MI) and the Barthel Index (BI). CR was assessed at baseline using the Cognitive Reserve Index (CRI) questionnaire. RESULTS: Considering all patients, a weak correlation was found between the CRI related to leisure time and MI evolution (r = 0.276; P = 0.02). Amongst the patients who performed a robotic rehabilitation, a moderate correlation emerged between the CRI related to working activities and MI evolution (r = 0.422; P = 0.02). CONCLUSIONS: Our results suggest that CR may influence the motor outcome. For each patient, CR and its subcategories should be considered in the choice between conventional and robotic treatment.

Novel outcome measures for Charcot-Marie-Tooth disease: validation and reliability of the 6-min walk test and StepWatch(™) Activity Monitor and identification of the walking features related to higher quality of life.

BACKGROUND AND PURPOSE: Charcot-Marie-Tooth (CMT) disease is the most common inherited neuropathy, but therapeutic options have been limited to symptom management. Past pharmacological trials have failed, possibly due to insensitive outcome measures (OMs). The aim of the current study was to evaluate the validity and reliability of the 6-min walk test (6MWT) and StepWatch(™) Activity Monitoring (SAM) with other previously validated OMs in CMT disease. METHODS: A prospective multicenter study was performed, consecutively enrolling 168 CMT patients (104 with CMT1A, 27 with CMT1B, 37 with X-linked CMT) from Italian centers specializing in CMT care. RESULTS: Statistical analysis showed that the 6MWT was highly related with all previously used OMs. Some, but not all, SAM parameters were related to commonly used OMs but may provide more information about quality of life. CONCLUSIONS: The current study demonstrated the validity and reliability of the 6MWT and SAM as OMs for CMT. Moreover, SAM provides data that correlate better with quality of life measures, making it useful in future rehabilitation trials.

Pain in stroke patients: characteristics and impact on the rehabilitation treatment. A multicenter cross-sectional study.

BACKGROUND: Post-stroke pain (PSP) is a common and disabling complication, difficult to treat, that often decreases patients' quality of life (QoL). The hypothesis is that PSP may negatively affect rehabilitation treatment. AIM: The aim of this paper was to quantify and characterize pain in a sample of post-stroke patients undergoing rehabilitation and to investigate the impact of pain in slowing down or discontinuing the rehabilitation program. DESIGN: Multicenter cross-sectional study. SETTING: Inpatients and outpatients of rehabilitation department. POPULATION: One hundred and six subacute and chronic stroke patients. METHODS: Pain intensity was measured with the NRS or the PAINAD (if cognitive/language impairment was present); pain characteristics were assessed with the DN4, and NPSI questionnaire. Qol was measured with the SF-36. A clinical assessment and a semi-structured questionnaire on pain occurrence, impact, and management was administered by the physiotherapist in charge of the patients and by the physician. RESULTS: Nearly 1/3 of the patients (32.9%) with normal cognitive functions and language reported pain occurrence after stroke; 81.8% of them had NRS≥3 and 31.8% DN4≥4 (meaning neuropathic origin of pain). In about 20% of the patients the PAINAD was used to measure pain; 17.4% of them presented a score ≥3. In 24.5% of our sample, pain influenced rehabilitation treatment. In 16% of the whole sample, pain influenced patients' attention during rehabilitation session. Patients with hypoesthesia presented significantly higher neuropathic pain scores than patients with normal sensory function. Regarding QoL, we found that patients with higher neuropathic pain showed more severe deterioration of mental aspects of QoL, where patients with higher nociceptive pain presented more severe deterioration of physical aspects of QoL. CONCLUSION: The results from this multicenter study showed that in about » of the patients, pain negatively influenced the rehabilitation program delaying the recovery and likely increasing the cost of rehabilitation. CLINICAL REHABILITATION IMPACT: Clinicians should pay more attention to pain, especially neuropathic pain, in post-stroke patients. Tailored pharmacological therapy, to treat and prevent pain, might improve patients' compliance during the rehabilitation process.

Abdominal acupuncture reduces laser-evoked potentials in healthy subjects.

OBJECTIVE: Acupuncture is known to reduce clinical pain, although the exact mechanism is unknown. The aim of the current study was to investigate the effect of acupuncture on laser-evoked potential amplitudes and laser pain perception. METHODS: In order to evaluate whether abdominal acupuncture is able to modify pain perception, 10 healthy subjects underwent a protocol in which laser-evoked potentials (LEPs) and laser pain perception were collected before the test (baseline), during abdominal acupuncture, and 15 min after needle removal. The same subjects also underwent a similar protocol in which, however, sham acupuncture without any needle penetration was used. RESULTS: During real acupuncture, both N1 and N2/P2 amplitudes were reduced, as compared to baseline (p<0.01). The reduction lasted up to 15 min after needle removal. Furthermore, laser pain perception was reduced during real acupuncture, although the difference was marginally significant (p=0.06). CONCLUSIONS: Our results show that abdominal acupuncture reduces LEP amplitude in healthy subjects. SIGNIFICANCE: Our results provide a theoretical background for the use of abdominal acupuncture as a therapeutic approach in the treatment of pain conditions. Future studies will have to be conducted in clinical painful syndromes, in order to confirm the analgesic effect of acupuncture in patients suffering from pain.

Rehabilitation for Charcot Marie tooth: a survey study of patients and familiar/caregiver perspective and perception of efficacy and needs.

BACKGROUND: Charcot Marie Tooth (CMT) disease is the most common inherited polyneuropathy. At the moment there is no pharmacological therapy for this pathology and the conservative treatment is mostly based on rehabilitation program. Moreover there is no medical consensus on it and the perception of its efficacy is mostly clinician-oriented. AIM: To evaluate, through ad hoc self-administered questionnaires, the patient and family/caregiver perspective on rehabilitation access and perceived benefit from it. DESIGN: Observational survey study. SETTING: Clinical and genetic records of in and out-patients of third level hospitals and a patients association (ACMT-Rete) and familiar/caregiver. POPULATION: Patients affected by CMT and familiar/caregiver. RESULTS: Questionnaires showed that patients perceive physical and mental benefit from rehabilitation, but also perceived that do not perform the best rehabilitation program for their pathology. Familiar and caregiver, are not sure that rehabilitation is effective for their kin, probably because the benefits are too small to be seen by someone other than the patient. CONCLUSION: The study shows as the lack of a consensus on rehabilitation tailored on CMT patients need is perceived by patients and familiar/caregiver. CLINICAL REHABILITATION IMPACT: The knowledge of patients perception is very important in order to obtain the best rehabilitation program for CMT disease.

Reliability of SFEMG in diagnosing myasthenia gravis: sensitivity and specificity calculated on 100 prospective cases.

OBJECTIVE: The study aimed to determine the utility of single-fibre electromyography (SFEMG) in the diagnosis of myasthenia gravis (MG) in subjects with a clinical suspicion of the disease. METHODS: We performed a prospective, single-blinded study on 100 consecutive patients. SFEMG was not considered a criterion in making the MG diagnosis. For all cases, a different physician than the one performing SFEMG made the diagnosis of MG. All subjects underwent standard SFEMG of a single muscle, the orbicularis oculi. RESULTS: SFEMG was abnormal in 67 of 100 patients. A final diagnosis of definite MG was made in 54 patients (30 men/24 women). SFEMG was positive in 53 of 54 patients diagnosed with MG. The sensitivity of SFEMG in diagnosing MG was 98% (95% CI: 0.94-1.02), while the specificity was 70% (95% CI: 0.54-0.86), with a positive predictive value of 79% (95% CI: 0.74-0.79) and a negative predictive value of 97% (95% CI: 0.94-0.99). CONCLUSIONS: In this cohort of patients, normal SFEMG findings were unlikely to occur in patients with MG. SIGNIFICANCE: SFEMG is not a confirmatory test for the diagnosis of MG, but it has a high negative predictive value in identifying patients without MG.

High ultrasound variability in chronic immune-mediated neuropathies. Review of the literature and personal observations.

Chronic immune-mediated neuropathies show high clinical variability. Diagnosis is based on clinical and neurophysiological studies, but recently ultrasound (US) of peripheral nerves has been shown to provide useful morphological information. US has already been shown to crucially influence diagnosis and clinical care in entrapment neuropathies, in traumatic nerve lesions and in tumors. The role of US in the evaluation of polyneuropathies is still not clearly defined, but increasing attention has recently been focused on the immune-mediated neuropathies and specific US measures (namely the intra- and inter-nerve cross-sectional area variability) have been developed. The aim of the current paper is to make a review of the available nerve US studies and provide data from personal observations in the most common chronic immune-mediated neuropathies.

Ultrasound assessment of sural nerve in Charcot-Marie-Tooth 1A neuropathy.

OBJECTIVE: Nerve ultrasound (US) has been used to study peripheral nerve disease, and increase of the cross-sectional area (CSA) has been described in demyelinating polyneuropathy. The objective of the current study is to characterise the US features of the sural nerve in a sample of Charcot-Marie-Tooth (CMT) 1A patients. METHODS: A total of 20 CMT1A patients were enrolled. As control group we studied 37 age- and sex-matched subjects. All patients underwent clinical examination, neurophysiology and US evaluation of the bilateral sural nerve and right ulnar nerve. US results were correlated with neurophysiology and clinical data. RESULTS: Sural nerve CSA was not increased in the majority of patients (70%), whereas an increased ulnar nerve CSA was present in the whole sample. Inverse relations were found between CSA of the ulnar nerve and body mass index (BMI) (p<0.0002, R=-0.8) and CSA of the sural nerve and age (right 0.006, R=-0.6, left 0.002, R=-0.6 and left and right p=0.00003, R=-0.4). CONCLUSIONS: US showed ulnar CSA enlargement and normal sural nerve CSA. SIGNIFICANCE: The significance of normal sural nerve CSA in CMT1A patients need to be further investigated, possibly through longitudinal studies.

Ultrasound as a useful tool in the diagnosis and management of traumatic nerve lesions.

OBJECTIVE: The possibility of depicting through ultrasound (US) the nerve and its surroundings should be very useful in traumatic nerve lesion (TNL) management. Our study aimed at evaluating the contribution of US as complementary tool in a neurophysiological laboratory for the diagnosis and management of TNL. METHODS: A total of 112 nerves from 98 consecutive patients with clinical suspicion of TNL were considered. Two independent and blinded clinicians, different from the examiners performing electrodiagnosis and US, classified clinical, neurophysiological and US findings and classified the contribution of US as follows: 'contributive' and 'non-contributive' if US confirmed the clinical and neurophysiological diagnosis or if US findings were unremarkable. RESULTS: US was 'contributive' (strongly modified the diagnostic and therapeutic path) in 58% of cases (n: 65) providing information on therapeutic approach (immediate or delayed surgery), diagnosis and follow-up. US specifically contributed to the (1) assessment of nerve continuity/discontinuity, hence neurotmesis/axonotmesis; (2) identification of aetiology; and (3) demonstration of multiple sites of damage. US was contributive mainly in cases with neurophysiological evidence of complete axonal damage. CONCLUSIONS: US should be used, when available, in all patients in whom TNL is suspected as it provides a more comprehensive diagnosis than neurophysiologic studies alone. Anatomical information is often crucial for choosing the most appropriate therapeutic strategies (and for surgical planning). SIGNIFICANCE: US can improve the outcome of TNL.

Consistence and discrepancy of neuropathic pain screening tools DN4 and ID-Pain.

Pain is a subjective condition that cannot be objectively measured; for this reason, self patient-perspective is crucial. Recently, several screening tools to discriminate between nociceptive and neuropathic pain have been developed. We aimed at assessing the consistence and discrepancy of two widely used screening tools, The Douleur Neuropathique 4 (DN4) and the 6-item questionnaire (ID-Pain), by comparing their ability in discriminating neuropathic from nociceptive pain. DN4 and ID-Pain were administered to 392 Italian patients attending 16 outpatient services for peripheral nerve diseases. Based on medical history, clinical findings and diagnostic tools, patients were divided into two groups (neuropathic and nociceptive). Globally, ID-Pain identified neuropathic pain in 60 % of patients (38 % probable, 22 % likely). Interestingly also DN4 diagnosed neuropathic pain in 60 % of cases. A discrepancy was observed in 16 % of cases. DN4 and ID-Pain resulted to be highly interrelated in the identification of neuropathic pain. Sensitivity of DN4 was 82 % and specificity was 81 %, while ID-Pain (considering both probable and likely groups) showed sensitivity 78 % and specificity 74 %. Reliable screening tools for neuropathic pain are well related between them; hence, they are available for researchers and clinicians who may choose the most appropriate for their activity. Since the gold standard for the diagnosis and treatment of neuropathic pain cannot do without a neurological evaluation, perhaps DN4, that includes physician objective measures, may help reducing the percentage of dubious cases. Conversely, when needing a more agile tool (not needing a physician) ID-Pain may be adopted.

Clinical usefulness of laser evoked potentials.

Several papers were published since the first clinical applications of laser evoked potentials (LEPs) in disorders of the nociceptive system. While studies produced until five years ago were mostly addressed at identifying lesions of the nociceptive system, more recent papers used LEPs as an instrumental tool for the diagnosis of neuropathic pain. LEPs have also proved useful in demonstrating the pathophysiological mechanisms underlying different types of neuropathic pain (e.g., paroxystic and ongoing neuropathic pain). This is of utmost importance, as pain treatment should take physiopathological mechanisms, rather than etiology into account. Although there are still some limits for the routine use of LEPs as a diagnostic tool, this review of the literature demonstrates that LEP recording has become mandatory for the functional assessment of patients with hypoalgesia or neuropathic pain.

Pregnancy-induced analgesia: a combined psychophysical and neurophysiological study.

BACKGROUND: To investigate changes in heat pain threshold and modifications in heat pain processing during pregnancy and labour, seventy-six nulliparous pregnant women were enrolled in two studies. METHODS: In the first study (psychophysical), 60 pregnant women underwent a quantitative sensory testing (QST) investigating heat perception in two body areas (right forearm and T10 dermatome) according to these groups: 32-33 gestational weeks (GW), 39-40 GW, early stage of active labour and 24 h after the delivery. In the other study (neurophysiological), contact heat-evoked potentials (CHEPs) were recorded in other 16 women at the 32nd GW and in 11 of these also at the 40th GW. RESULTS: The psychophysical study showed that heat pain threshold was significantly increased at the forearm at 32-33 GW (median ± IQR: 39.6 ± 0.7 °C), at 39-40 GW (40.6 ± 1.1 °C) and at early stage of active labour (40.8 ± 1.5 °C) as compared to 20 non-pregnant controls (p < 0.001). Heat pain threshold tested at T10 level was significantly increased at 32-33 GW (41.0 ± 1.6 °C), at 39-40 GW (42.1 ± 1.8 °C), and at early stage of active labour (42.3 ± 1.3 °C) as compared to the non-pregnant women (p < 0.001). The N2-P2 CHEP amplitude (main negative N2 and positive P2 components of the vertex biphasic potential) recorded from the pregnant women was significantly lower at the 40th than at the 32nd GW, after stimulation of both the forearm (p < 0.001) and the abdomen (p < 0.001). CONCLUSIONS: In pregnant women, there is a progressive increase of heat pain threshold and a reduction of the CHEP amplitude, suggesting that a general inhibitory mechanism may be involved.

Contribution of ultrasound in the assessment of nerve diseases.

BACKGROUND AND PURPOSE: Recently, ultrasound (US) has been used to assess the peripheral nervous system; however, there is no real study about its possible significant role in routine practice. Our study aims to assess the contribution of US as a routine tool in a neurophysiological laboratory. METHODS: The study assesses 130 patients who presented clinical suspicion of peripheral nerve diseases, excluding motor neuron disease, radiculopathy, hereditary and acquired polyneuropathy. All patients were clinically, neurophysiologically and sonographically assessed in the same session by the same neurologist/neurophysiologist. To avoid interpretation bias, two independent and blinded clinicians, different than the examiners performing electrodiagnosis and US, reviewed clinical, neurophysiological and US findings (also data about follow-up, when available) and classified the contribution of US as follows: Contributive (US had influence on the diagnostic and therapeutic strategies), Confirming (US confirmed the clinical and neurophysiological diagnosis), Non-Confirming (US findings were normal) and Incorrect (US findings led to incorrect diagnosis). RESULTS: US impacted, namely modified the diagnostic and therapeutic path in 42.3% of cases (55 patients); US had a confirmatory role in 40% (52 patients); US did not confirm clinical and neurophysiological diagnosis in 17.7% (23 cases); no incorrect US findings were observed. CONCLUSION: US complements neurophysiological assessment even in routine practice, and this confirms the increasing interest in US for a multidimensional evaluation of peripheral nerve system diseases.

Evidence of different spinal pathways for the warmth evoked potentials.

OBJECTIVE: To investigate the presence of multiple spinothalamic pathways for warmth in the human spinal cord. METHODS: Laser evoked potentials to C-fiber stimulation (C-LEPs) were recorded in 15 healthy subjects after warmth stimulation of the dorsal midline at C5, T2, T6, and T10 vertebral levels. This method allowed us to calculate the spinal conduction velocity (CV) in two different ways: (1) the reciprocal of the slope of the regression line was obtained from the latencies of the different C-LEP components, and (2) the distance between C5 and T10 was divided by the latency difference of the responses at the two sites. In particular, we considered the C-N1 potential, generated in the second somatosensory (SII) area, and the late C-P2 response, generated in the anterior cingulate cortex (ACC). RESULTS: The calculated CV of the spinal fibers generating the C-N1 potential (around 2.5m/s) was significantly different (p<0.01) from the one of the pathway producing the P2 response (around 1.4m/s). CONCLUSIONS: Our results suggest that the C-N1 and the C-P2 components are generated by two parallel spinal pathways. SIGNIFICANCE: Warmth sensation is subserved by parallel spinothalamic pathways, one probably reaching the SII area, the other the ACC.

Occurrence and characterization of Pain in immune-mediated neuropathies: a multicentre prospective study.

BACKGROUND: pain is a common symptom of peripheral neuropathies that may severely affect patients' Quality of Life. Pain questionnaires, based on verbal descriptors, are a useful way to investigate it. METHODS: we performed a multicentre study through validated measures to characterize pain in a sample of consecutive patients affected by immune-mediated neuropathies. RESULTS: ninety-three patients were enrolled in 16 Italian centres. Based on the numeric rating scale, almost half of the patients complained of moderate pain and one-third of the patients severe pain. Overall, up to 50% of our patients with immune-mediated neuropathies complained of neuropathic pain. The most common neuropathic symptoms were paraesthesia/dysesthesia and superficial spontaneous pain. Surprisingly, also patients with neuropathies commonly thought to be painless (such as multifocal motor neuropathy) reported discomfort and painful symptoms. CONCLUSIONS: pain questionnaires should be considered in the clinical evaluation of immune-mediated neuropathies, also when evaluating therapy efficacy, because they may provide clinicians with useful information on painful symptoms and patients' quality of life.