Depression Prevalence in Neuropathic Pain and Its Impact on the Quality of Life.

Introduction: The management of neuropathic pain remains complex, generally because of the psychiatric comorbidity that is often underdiagnosed. The objectives of our work were to determine the link between depression and the characteristics of NP on the one hand and quality of life on the other hand, in a sample of subjects consulting for neuropathic pain (NP) regardless of etiology. Methods: We conducted a cross-sectional study involving 61 neuropathic pain consulting patients in whom we assessed five parameters, namely, neuropathic pain based on DN4, pain intensity using EVA, anxiety, and depression according to the HADS and quality of life. Results: The study population mean age was 52.71 ± 14.29 years while the sex ratio (m/f) was 0.52. The neuropathic pain's most common etiologies were postherpetic pain, carpal tunnel syndrome, and diabetic neuropathy. Depression and anxiety prevailed by 65.6% and 73.7%, respectively. The quality of life was impaired with average SF-12 physical and mental scores of 33.76 ± 8.03 and 37.78 ± 11.52, respectively. The overall mean BPI score was 5.53 ± 1.76. Patients with high DN4 scores were significantly more depressed (p=0.025). A significantly positive association was found between the depression score and the pain intensity (p=0.001, r = 0.41). Depressed subjects had a poor quality of life according to SF-12 and BPI. Conclusion: Given the depressive comorbidity impact on the neuropathic pain components as well as the quality of life, screening for this comorbidity should be part of the baseline ND assessment.

The Clinical Features of Painful Small-Fiber Neuropathy Suggesting an Origin Linked to Primary Sjögren's Syndrome.

OBJECTIVE: We attempted to determine whether clinical features could differentiate painful small-fiber neuropathy related to primary Sj€ogren's syndrome (pSS-SFN) from idiopathic SFN (idio-SFN). METHODS: Validated clinical questionnaires and neurophysiological investigations specific for pain and SFN assessment were performed in 25 patients with pSS-SFN and 25 patients with idio-SFN. RESULTS: Patients with idio-SFN had more frequent severe burning sensations and higher mean anxiety scores and daily pain intensity compared to patients with pSSSFN. Conversely, patients with pSS-SFN had reduced electrochemical skin conductance measured by Sudoscan_, and almost half of them had the sensation of walking on cotton wool. CONCLUSION: Our results suggest that idio-SFN more specifically involved small sensory fibers than pSS-SFN, in which subtle dysfunction of larger sensory fibers and damage of distal autonomic sudomotor innervation may occur. A practical algorithm is proposed to help to differentiate SFN associated with pSS from idio-SFN, based on information very easy to obtain by clinical interview.

Coaching of lifestyle recommendations improves sensory neurophysiological parameters in neuropathies related to glycemic disorder or metabolic syndrome. A pilot study.

OBJECTIVES: Metabolic abnormalities, such as, glycemic disorders and metabolic syndrome (GDMS) are one of the main causes of peripheral neuropathies. The objective of this study was to evaluate the impact of adding specific coaching care (CC) to standard care (SC) of therapeutic education based on lifestyle recommendations for neuropathies associated with GDMS. METHODS: This prospective randomized study included two groups of four patients (SC vs. CC) with examiners blinded to group allocation. The SC group had one day of therapeutic education on lifestyle measures (physical activity and diet recommendations) followed by only one phone call of reinforcement. The CC group received an additional weekly phone call of reinforcement for 3 months. Clinical, biological and neurophysiological variables were compared between the two groups at baseline and for the percentage of change at 3 months. RESULTS: All patients (4 men and 4 women) had diabetes or pre-diabetes, which was associated with metabolic syndrome in 5 cases. There was no difference on any variable at baseline, but at 3 months, Mann-Whitney test showed a difference (P=0.0008) between the two groups regarding the sensory neurophysiological variable, which deteriorated in the SC group (median: -6.0%) and improved in the CC group (median: +12.4%). No significant difference was observed between the two groups for the other variables at 3 months. CONCLUSION: The weekly coaching of recommendations for lifestyle measures over a period of three months allows an improvement of GDMS neuropathies, at least in terms of sensory aspects, as evidenced by neurophysiological assessments.

Characterization of Neuropathic Pain in Primary Sjögren's Syndrome with Respect to Neurophysiological Evidence of Small-Fiber Neuropathy.

OBJECTIVE: To determine whether clinical features of neuropathic pain differ with respect to the presence of small-fiber neuropathy (SFN) in patients with primary Sjögren's syndrome (pSS). METHODS: We compared the clinical presentation of neuropathic pain between 15 patients with pSS and SFN detected by neurophysiological tests (laser-evoked potentials, cold and warm detection thresholds, sympathetic skin responses, and electrochemical skin conductance) and 15 patients with pSS but no neurophysiological evidence of SFN. RESULTS: The patients with SFN had more intense squeezing and pressure sensations and more frequent dynamic mechanical allodynia (pain provoked by brushing) than the patients without SFN. Restless leg syndrome was also more frequently observed in patients with SFN, who had pain aggravated at rest that improved by moving. CONCLUSIONS: These findings are in favor of the sensitization of relatively spared large Aß-fibers and second-order nociceptive neurons in patients with SFN. On the other hand, burning sensations, which rather reveal sensitization of small nociceptive fibers, were observed whether SFN was present or not. Thus, some discriminating clinical features may help to suggest the presence of SFN in patients with pSS and chronic neuropathic pain.

The value of electrochemical skin conductance measurement using Sudoscan® in the assessment of patients with familial amyloid polyneuropathy.

OBJECTIVE: To reappraise the value of electrochemical skin conductance (ESC) measurement by Sudoscan® to assess the distal involvement of small autonomic fibers in familial amyloid polyneuropathy (FAP) due to various transthyretin (TTR) mutations. METHODS: ESC was measured at both hands and feet in 126 patients with either Val30Met (n = 65) or non-Val30Met (n = 61) TTR mutation. This series included clinically asymptomatic (n = 21) and paucisymptomatic (n = 30) patients, as well as patients with moderate (n = 37) or advanced (n = 38) TTR-FAP. RESULTS: ESC measures did not differ between patients according to the type of TTR variant and were reduced in 24% of clinically asymptomatic patients, 40% of paucisymptomatic patients, 65% of patients with moderate TTR-FAP, and 92% of patients with advanced TTR-FAP. ESC measures were found to correlate with patients' clinical status, especially assessed by the Neuropathy Impairment Score and Karnofsky Performance Status. CONCLUSION: ESC measures well correlate with the severity of TTR-FAP and could provide early marker of the disease. SIGNIFICANCE: ESC measures appear to be relevant to evaluate distal autonomic involvement in the context of amyloidosis.

The ulnar ratio as a sensitive and specific marker of acute inflammatory demyelinating polyneuropathy.

OBJECTIVES: To explore the value of a novel sensory criterion, the ulnar ratio - defined as the SNAP amplitude of the palmar cutaneous (pUN) over that of the dorsal branch (dUN) of the ulnar nerve - as a predictor of Acute Inflammatory Demyelinating Polyneuropathy (AIDP). METHODS: We prospectively included 22 patients with AIDP, 20 patients with diabetic peripheral neuropathy (DPN), and 18 controls. Eligible subjects underwent nerve conduction studies including, among others, the dUN, pUN, and sural nerve. RESULTS: A sural sparing pattern was found in 72% of AIDP cases. The ulnar ratio was significantly lower in patients with AIDP compared to those with DPN or controls. The ROC curve area to discriminate AIDP (versus controls and diabetics together) was higher with the ulnar ratio and pUN compared to dUN. An ulnar ratio ≥ 0.78 seems to be the best threshold to rule out the diagnosis of AIDP, with a specificity of 100% and a sensitivity of 87%. The ulnar ratio was equally reliable in the subgroup of patients presenting within a week of symptoms onset. CONCLUSION: The ulnar ratio is a highly sensitive and specific marker of AIDP and can help confirm the diagnosis when direct signs of demyelination are lacking. SIGNIFICANCE: Incorporating specific sensory abnormalities, such as the ulnar ratio, in the electrodiagnostic criteria of AIDP could enhance their reliability.

A reappraisal of small- and large-fiber damage in carpal tunnel syndrome: New insights into the value of the EMLA test for improving diagnostic sensitivity.

OBJECTIVES: To reappraise the respective involvement of small- and large-fiber damage in carpal tunnel syndrome (CTS) and to determine the diagnostic sensitivity of autonomic tests compared to conventional nerve conduction study (NCS). METHODS: Thirty-two manual workers complaining of at least unilateral CTS were enrolled. They underwent clinical interview and completed the symptom severity scale of the Boston CTS Questionnaire (sssBCTQ) and the Neuropathic Pain Symptom Inventory (NPSI). In addition, transcarpal NCS was performed to investigate large sensory and motor fibers of the median nerve, while small autonomic fibers were assessed by recording sympathetic skin reflexes (SSR) at the palm and by grading skin wrinkling in response to eutectic mixture of local anesthetic (EMLA) cream application at the pulp of the index finger. For each neurophysiological variable, sensitivity and specificity values for the diagnosis of CTS were calculated and clinical correlations were studied. RESULTS: Among 64 hands examined, 36 were clinically symptomatic, while 22 were clinically asymptomatic and served as controls. Among all the neurophysiological variables studied, only the values of transcarpal sensory nerve conduction velocity and the EMLA test grade were found to be more altered in clinically symptomatic hands, with also a trend towards prolonged distal motor latency. Overall, for the diagnosis of clinically symptomatic CTS, NCS, SSR, and the EMLA test had a sensitivity of 66.7%, 22.2%, and 69.4%, respectively, and a specificity of 72.7%, 90.9%, and 50%, respectively. Combining NCS and the EMLA test led to a sensitivity of 88.9% and a specificity of 45.4%. The sssBCTQ (r=-0.34, P=0.009) and the total NPSI score (r=-0.41, P=0.001) correlated to a more altered EMLA test grade, but not to any NCS or SSR variables. In symptomatic hands, burning sensation was associated with more severe small-fiber lesion, while other pain and sensory symptoms were rather found to be reduced in case of large-fiber damage, evidenced by NCS alteration. CONCLUSIONS: This study confirms the discrepancy between conventional NCS results and clinical presentation of CTS, but still suggests a major involvement of Aß fibers in the positive sensory symptoms of CTS, excepting burning sensation. On the other hand, the EMLA test was found to correlate with clinical data and to be able to improve sensitivity of neurophysiological investigation in diagnosing CTS.

Tremor in multiple sclerosis: The intriguing role of the cerebellum.

Tremor is frequently encountered in multiple sclerosis (MS) patients. However, its underlying pathophysiological mechanisms remain poorly understood. Our aim was to assess the potential role of the cerebellum and brain stem structures in the generation of MS tremor.We performed accelerometric (ACC) and electromyographic(EMG) assessment of tremor in 32MS patients with manual clumsiness. In addition to clinical examination, patients underwent a neurophysiological exploration of the brainstem and cerebellar functions,which consisted of blink and masseter inhibitory reflexes, cerebello-thalamo-cortical inhibition (CTCi), and somatosensory evoked potentials. Tremor was clinically visible in 18 patients and absent in 14. Patients with visible tremor had more severe score of ataxia and clinical signs of cerebellar dysfunction, as well as a more reduced CTCi on neurophysiological investigation. However, ACC and EMG recordings confirmed the presence of a real rhythmic activity in only one patient. In most MS patients, the clinically visible tremor corresponded to a pseudorhythmic activity without coupling between ACC and EMG recordings. Cerebellar dysfunction may contribute to the occurrence of this pseudorhythmic activity mimicking tremor during posture and movement execution.

Cortical excitability changes over time in progressive multiple sclerosis.

In 25 patients with progressive forms of multiple sclerosis (MS), motor cortex excitability was longitudinally studied over one year by means of transcranial magnetic stimulation (TMS). The following TMS parameters were considered: resting and active motor thresholds (MTs), input-output curve, short-interval intracortical inhibition (SICI), and intracortical facilitation. Clinical evaluation was based on the Expanded Disability Status Scale (EDSS). In the 16 patients not receiving disease-modifying drugs, the EDSS score worsened, resting MT increased, and SICI decreased. By contrast, no clinical for neurophysiological changes were found over time in the nine patients receiving immunomodulatory therapy. The natural course of progressive MS appears to be associated with a decline in cortical excitability of both pyramidal neurons and inhibitory circuits. This pilot study based on a small sample suggests that disease-modifying drugs may allow cortical excitability to remain stable, even in patients with progressive MS.

Stroke rehabilitation using noninvasive cortical stimulation: motor deficit.

Noninvasive cortical stimulation (NICS) has been used during the acute, postacute and chronic poststroke phases to improve motor recovery in stroke patients having upper- and/or lower-limb paresis. This paper reviews the rationale for using the different NICS modalities to promote motor stroke rehabilitation. The changes in cortical excitability after stroke and the possible mechanisms of action of cortical stimulation in this context are outlined. A number of open and placebo-controlled trials have investigated the clinical effect of repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) of the primary motor cortex in patients with motor stroke. These studies attempted to improve motor performance by increasing cortical excitability in the stroke-affected hemisphere (via high-frequency rTMS or anodal tDCS) or by decreasing cortical excitability in the contralateral hemisphere (via low-frequency rTMS or cathodal tDCS). The goal of these studies was to reduce the inhibition exerted by the unaffected hemisphere on the affected hemisphere and to then restore a normal balance of interhemispheric inhibition. All these NICS techniques administered alone or in combination with various methods of neurorehabilitation were found to be safe and equally effective at the short term on various aspects of poststroke motor abilities. However, the long-term effect of NICS on motor stroke needs to be further evaluated before considering the use of such a technique in the daily routine management of stroke.

Stroke rehabilitation using noninvasive cortical stimulation: aphasia.

Poststroke aphasia results from the lesion of cortical areas involved in the motor production of speech (Broca's aphasia) or in the semantic aspects of language comprehension (Wernicke's aphasia). Such lesions produce an important reorganization of speech/language-specific brain networks due to an imbalance between cortical facilitation and inhibition. In fact, functional recovery is associated with changes in the excitability of the damaged neural structures and their connections. Two main mechanisms are involved in poststroke aphasia recovery: the recruitment of perilesional regions of the left hemisphere in case of small lesion and the acquisition of language processing ability in homotopic areas of the nondominant right hemisphere when left hemispheric language abilities are permanently lost. There is some evidence that noninvasive cortical stimulation, especially when combined with language therapy or other therapeutic approaches, can promote aphasia recovery. Cortical stimulation was mainly used to either increase perilesional excitability or reduce contralesional activity based on the concept of reciprocal inhibition and maladaptive plasticity. However, recent studies also showed some positive effects of the reinforcement of neural activities in the contralateral right hemisphere, based on the potential compensatory role of the nondominant hemisphere in stroke recovery.

Stroke rehabilitation using noninvasive cortical stimulation: hemispatial neglect.

The rehabilitation of neuropsychological sequels of cerebral stroke such as hemispatial neglect by noninvasive cortical stimulation (NICS) attracts increasing attention from the scientific community. The NICS techniques include primarily repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). They are based on the concept of either reactivating a hypoactive cortical region affected by the stroke (the right hemisphere in case of neglect) or reducing cortical hyperactivity of the corresponding cortical region in the contralateral hemisphere (the left hemisphere). In the studies published to date on the topic of neglect rehabilitation, rTMS was used to inhibit the left parietal cortex and tDCS to either activate the right or inhibit the left parietal cortex. Sham-controlled NICS studies assessed short-term effects, whereas long-term effects were only assessed in noncontrolled rTMS studies. Further controlled studies of large series of patients are necessary to determine the best parameters of stimulation (including the optimal cortical target location) according to each subtype of neglect presentation and to the time course of stroke recovery. To date, even if there are serious therapeutic perspectives based on imaging data and experimental studies, the evidence is not compelling enough to recommend any particular NICS protocol to treat this disabling condition in clinical practice.