Original article: adolescent dietary patterns derived using principal component analysis and neuropsychological functions: a cross-sectional analysis of Walnuts Smart Snack cohort.

A balanced diet is relevant for neuropsychological functioning. We aimed to analyze the association between dietary patterns and neuropsychological outcomes in a sample of healthy adolescents of the Walnuts Smart Snack (WSS) cohort from Barcelona city. We performed principal components analysis (PCA) to determine dietary patterns in the adolescent sample using a food frequency questionnaire (60 items). Multiple linear regression models were performed to analyze the association between PCA dietary patterns with neuropsychological outcomes: Strengths and Difficulties (SDQ) externalizing and internalizing scores, Attention Network Test (ANT) Impulsivity Index and Emotional Recognition Task (ERT) scores. We additionally adjusted the models for child sex, age, body mass index (BMI), physical activity and maternal education. Six dietary patterns were identified in PCA analyses. "low consumption of calorie-dense foods" dietary pattern had a negative association (protective) with the both SDQ outcomes (p value < 0.001) and "Nuts" dietary pattern showed a negative (protective) association with impulsivity index ( ß 1 = -24.60, 95% CI = -36.80, -12.41, p value < 0.001). Overall, our main results suggest that healthy dietary patterns, including higher intakes of "nuts" and a preference of "low consumption of calorie-dense foods" dietary patterns, could provide a beneficial association with neuropsychological functions during the adolescence period. The associations may include improvements of externalizing and internalizing problem symptoms, and impulsivity.

Motor polyradiculopathy during pembrolizumab treatment of metastatic melanoma.

INTRODUCTION: Pembrolizumab, a monoclonal antibody directed against the immune checkpoint programmed cell death-1 receptor (PD-1), has improved survival in patients with advanced melanoma. Neuromuscular immune-mediated side effects have been rarely reported. METHODS: We describe a 44-year-old man with metastatic melanoma who presented with progressive muscle weakness after 23 doses of pembrolizumab. RESULTS: The patient developed asymmetric, proximal muscle weakness and atrophy in all four limbs. Cerebrospinal fluid examination showed albuminocytologic dissociation. MRI revealed contrast enhancement of the lumbosacral roots. Electrodiagnostic studies demonstrated widespread fibrillation potentials in all four limbs, suggesting a generalized motor polyradiculopathy. Despite pembrolizumab discontinuation and treatment with steroids and intravenous immunoglobulin, limb weakness worsened. Electrodiagnostic studies were repeated, and showed marked and diffuse axonal motor damage. Seven weeks after clinical onset the patient was treated with plasma exchanges. He showed no further deterioration. DISCUSSION: We report a severe motor polyradiculopathy associated with an anti-PD-1 agent that expands the spectrum of neuromuscular complications of this class of drugs. Muscle Nerve 56: E162-E167, 2017.

Defective sensorimotor integration in preparation for reaction time tasks in patients with multiple sclerosis.

Slowness of voluntary movements in patients with multiple sclerosis (MS) may be due to various factors, including attentional and cognitive deficits, delays in motor conduction time, and impairment of specific central nervous system circuits. In 13 healthy volunteers and 20 mildly disabled, relapsing-remitting MS patients, we examined simple reaction time (SRT) tasks requiring sensorimotor integration in circuits involving the corpus callosum and the brain stem. A somatosensory stimulus was used as the imperative signal (IS), and subjects were requested to react with either the ipsilateral or the contralateral hand (uncrossed vs. crossed SRT). In 33% of trials, a startling auditory stimulus was presented together with the IS, and the percentage reaction time change with respect to baseline SRT trials was measured (StartReact effect). The difference between crossed and uncrossed SRT, which requires interhemispheric conduction, was significantly larger in patients than in healthy subjects (P = 0.021). The StartReact effect, which involves activation of brain stem motor pathways, was reduced significantly in patients with respect to healthy subjects (uncrossed trials: P = 0.015; crossed trials: P = 0.005). In patients, a barely significant correlation was found between SRT delay and conduction abnormalities in motor and sensory pathways (P = 0.02 and P = 0.04, respectively). The abnormalities found specifically in trials reflecting interhemispheric transfer of information, as well as the evidence for reduced subcortical motor preparation, indicate that a delay in reaction time execution in MS patients cannot be explained solely by conduction slowing in motor and sensory pathways but suggest, instead, defective sensorimotor integration mechanisms in at least the two circuits examined.

Cutaneous autonomic denervation in Parkinson's disease.

Numerous studies have detailed involvement of the peripheral autonomic nervous system (PANS) in Parkinson's disease (PD). We assessed autonomic innervation of dermal annexes through quantitative fluorescence measurement from skin obtained via punch biopsies at distal leg region in PD and control subjects. We defined a ratio between the area corresponding to protein gen product (PGP) immunoreactivity and the area corresponding to blood vessel or sweat gland as a quantitative measure of autonomic innervation. Presence of alpha-synuclein (AS) deposits in dermis and hypodermis was also assessed by immunohistochemistry. Skin biopsies form six PD patients and six healthy controls were studied. Autonomic innervation scores were lower in PD than in controls in both blood vessels and sweat glands. No AS or phosphorylated AS (pAS) immunoreactivity was detected in dermis or hypodermis in any of the studied subjects. The results of this investigation suggest that autonomic innervation of dermal annexes in living patients with PD is reduced compared to controls. AS or pAS deposits were not found in dermis or hypodermis suggesting that distal leg skin study is not useful for in vivo detection of AS in PD.

Effects of postural and voluntary muscle contraction on modulation of the soleus H reflex by transcranial magnetic stimulation.

Modulation of spinal reflexes depends largely on the integrity of the corticospinal tract. A useful method to document the influence of descending tracts on reflexes is to examine the effects of transcranial magnetic stimulation (TMS) on the soleus H reflex elicited by posterior tibial nerve electrical stimuli (PTS). In 12 healthy volunteers, we investigated how postural or voluntary muscle contraction modified such descending modulation. We first characterized the effects of TMS at 95 % of motor threshold for leg responses on the H reflex elicited by a preceding PTS at inter-stimuli intervals (ISIs) between 0 and 120 ms at rest and, then, during voluntary plantar flexion (pf), dorsal flexion (df), and standing still (ss). During pf, there was an increase in the facilitation of the H reflex at ISIs 0-20 ms. During df, there were no effects of TMS on the H reflex. During ss, there was inhibition at ISIs 40-60 ms. Our observations suggest that muscle contraction prevails over the baseline effects of TMS on the soleus H reflex. While contraction of the antagonist (df) suppressed most of the effects, contraction of the agonist had different effects depending on the type of activity (pf or ss). The characterization of the interaction between descending corticospinal volleys and segmental peripheral inputs provides useful information on motor control for physiological research and further understanding of the effects of spinal cord lesions.

Small fibre pathology in patients with fibromyalgia syndrome.

Fibromyalgia syndrome is a clinically well-characterized chronic pain condition of high socio-economic impact. Although the pathophysiology is still unclear, there is increasing evidence for nervous system dysfunction in patients with fibromyalgia syndrome. In this case-control study we investigated function and morphology of small nerve fibres in 25 patients with fibromyalgia syndrome. Patients underwent comprehensive neurological and neurophysiological assessment. We examined small fibre function by quantitative sensory testing and pain-related evoked potentials, and quantified intraepidermal nerve fibre density and regenerating intraepidermal nerve fibres in skin punch biopsies of the lower leg and upper thigh. The results were compared with data from 10 patients with monopolar depression without pain and with healthy control subjects matched for age and gender. Neurological and standard neurophysiological examination was normal in all patients, excluding large fibre polyneuropathy. Patients with fibromyalgia syndrome had increased scores in neuropathic pain questionnaires compared with patients with depression and with control subjects (P < 0.001 each). Compared with control subjects, patients with fibromyalgia syndrome but not patients with depression had impaired small fibre function with increased cold and warm detection thresholds in quantitative sensory testing (P < 0.001). Investigation of pain-related evoked potentials revealed increased N1 latencies upon stimulation at the feet (P < 0.001) and reduced amplitudes of pain-related evoked potentials upon stimulation of face, hands and feet (P < 0.001) in patients with fibromyalgia syndrome compared to patients with depression and to control subjects, indicating abnormalities of small fibres or their central afferents. In skin biopsies total (P < 0.001) and regenerating intraepidermal nerve fibres (P < 0.01) at the lower leg and upper thigh were reduced in patients with fibromyalgia syndrome compared with control subjects. Accordingly, a reduction in dermal unmyelinated nerve fibre bundles was found in skin samples of patients with fibromyalgia syndrome compared with patients with depression and with healthy control subjects, whereas myelinated nerve fibres were spared. All three methods used support the concept of impaired small fibre function in patients with fibromyalgia syndrome, pointing towards a neuropathic nature of pain in fibromyalgia syndrome.

Impaired small fiber conduction in patients with Fabry disease: a neurophysiological case-control study.

BACKGROUND: Fabry disease is an inborn lysosomal storage disorder which is associated with small fiber neuropathy. We set out to investigate small fiber conduction in Fabry patients using pain-related evoked potentials (PREP). METHODS: In this case-control study we prospectively studied 76 consecutive Fabry patients for electrical small fiber conduction in correlation with small fiber function and morphology. Data were compared with healthy controls using non-parametric statistical tests. All patients underwent neurological examination and were investigated with pain and depression questionnaires. Small fiber function (quantitative sensory testing, QST), morphology (skin punch biopsy), and electrical conduction (PREP) were assessed and correlated. Patients were stratified for gender and disease severity as reflected by renal function. RESULTS: All Fabry patients (31 men, 45 women) had small fiber neuropathy. Men with Fabry disease showed impaired cold (p < 0.01) and warm perception (p < 0.05), while women did not differ from controls. Intraepidermal nerve fiber density (IENFD) was reduced at the lower leg (p < 0.001) and the back (p < 0.05) mainly of men with impaired renal function. When investigating A-delta fiber conduction with PREP, men but not women with Fabry disease had lower amplitudes upon stimulation at face (p < 0.01), hands (p < 0.05), and feet (p < 0.01) compared to controls. PREP amplitudes further decreased with advance in disease severity. PREP amplitudes and warm (p < 0.05) and cold detection thresholds (p < 0.01) at the feet correlated positively in male patients. CONCLUSION: Small fiber conduction is impaired in men with Fabry disease and worsens with advanced disease severity. PREP are well-suited to measure A-delta fiber conduction.

Multifocal Transcranial Direct Current Stimulation in Primary Progressive Aphasia Does Not Provide a Clinical Benefit Over Speech Therapy.

BACKGROUND: Primary progressive aphasia (PPA) is a group of neurodegenerative disorders including Alzheimer's disease and frontotemporal dementia characterized by language deterioration. Transcranial direct current stimulation (tDCS) is a non-invasive intervention for brain dysfunction. OBJECTIVE: To evaluate the tolerability and efficacy of tDCS combined with speech therapy in the three variants of PPA. We evaluate changes in fMRI activity in a subset of patients. METHODS: Double-blinded, randomized, cross-over, and sham-controlled tDCS study. 15 patients with PPA were included. Each patient underwent two interventions: a) speech therapy + active tDCS and b) speech therapy + sham tDCS stimulation. A multifocal strategy with anodes placed in the left frontal and parietal regions was used to stimulate the entire language network. Efficacy was evaluated by comparing the results of two independent sets of neuropsychological assessments administered at baseline, immediately after the intervention, and at 1 month and 3 months after the intervention. In a subsample, fMRI scanning was performed before and after each intervention. RESULTS: The interventions were well tolerated. Participants in both arms showed clinical improvement, but no differences were found between active and sham tDCS interventions in any of the evaluations. There were trends toward better outcomes in the active tDCS group for semantic association and reading skills. fMRI identified an activity increase in the right frontal medial cortex and the bilateral paracingulate gyrus after the active tDCS intervention. CONCLUSION: We did not find differences between active and sham tDCS stimulation in clinical scores of language function in PPA patients.

Brainstem dysfunction in variegate porphyria.

INTRODUCTION: Variegate porphyria (VP) is a rare metabolic disorder that may present as an acute predominantly motor neuropathy. Cranial nerves and brainstem functions have been only scarcely studied. METHODS: Brainstem reflexes were examined in symptomatic and non-symptomatic VP mutation carriers of a single family. RESULTS: Similar results were found in the 2 patients with a history of porphyric crises. The blink reflex showed an absence of late responses (R2 and R2c) to stimulation of both sides. The masseter inhibitory reflex showed reduced inhibition of the second phase. The jaw jerk was normal. The asymptomatic carriers did not show any of the abnormalities just noted. CONCLUSIONS: Our results are compatible with a central lower pons-upper medulla disorder in the brainstem. We hypothesize that brainstem dysfunction in VP patients with a history of porphyric crises may be due to neurotoxic effects of porphyrin precursors as well as subclinical osmolarity changes due to hyponatremia.

The effects of transcranial magnetic stimulation on vibratory-induced presynaptic inhibition of the soleus H reflex.

A single-pulse transcranial magnetic stimulus (TMS) may induce contraction in many muscles of the body at the same time. This is specially the case when using the double-cone coil to obtain the motor evoked potentials in leg muscles. Even if intensity is kept below threshold for the soleus muscle, TMS induces facilitation of the soleus H reflex that is separated into two phases: the first, peaking at 10-20 ms and the second, peaking at 70-90 ms. We investigated the possibility that TMS-induced facilitation of the H reflex was related, at least in part, to the reafferentation volley reaching the alpha motoneuron after synchronized contraction of other muscles in the body. To test this hypothesis, we examined the effects of vibration on the TMS-induced facilitation of the soleus H reflex. As expected, vibration applied over the triceps tendon caused a significant reduction in H reflex amplitude: 42.4 ± 6.4 % of control values. When conditioned by TMS at intervals corresponding to the first phase, the H reflex was facilitated to the same extent in both conditions: with and without vibration. However, at intervals corresponding to the second facilitation phase, there was a significantly reduced facilitation with vibration. These differential effects of vibration on the two phases of the TMS-induced facilitation of the H reflex indicate a different mechanism for each facilitation phase. The first phase could result from direct corticospinal excitatory input, while the second phase might depend on inputs via Ia afferents from heteronymous muscles.

Mitochondrial loss indicates early axonal damage in small fiber neuropathies.

Evaluation of nerve fibers in the skin provides a useful tool for the diagnosis of small fiber neuropathies (SFNs). Our aim was to determine whether mitochondria are involved in SFN, indicating early axonal damage. We quantified mitochondrial respiratory chain complex IV (OXPHOS) and axonal (PGP 9.5) fluorescence on skin sections from 32 SFN patients and 14 healthy controls. Also, a group of six patients were recruited before and after 30-day treatment with the mitotoxic antibiotic linezolid. We measured the co-localization of OXPHOS within the intraepidermal and subpapillary dermal axons (PGP-immunoreactive [PGP-ir]). SFN patients with relatively preserved intraepidermal nerve fibers (SFN borderline) showed statistically significant reduction of OXPHOS (50.5 ± 33.9 µm(2) vs. 107.6 ± 81 µm(2) in controls, p < 0.02). A positive correlation was found between both PGP-ir and OXPHOS in controls (Pearson's coefficient r = 0.59, p < 0.001), whereas such correlation was absent in SFN. With respect to baseline measurements, linezolid therapy increased both PGP-ir and OXPHOS, which could be considered an initial compensatory toxic-induced response. This study set out to identify a possible marker of axonal pre-degenerative state in SFN borderline patients.

Adaptation to tonic heat in healthy subjects and patients with sensory polyneuropathy.

Background Adaptation to a constant sensory stimulus involves many sites along the path of sensory volleys towards perception. The evaluation of such phenomenon may be of clinical interest. We studied adaptation to a constant temperature stimulus in healthy subjects to set normative data and in patients with sensory polyneuropathy (SPN), as proof of concept. Methods Twenty-six healthy subjects and 26 patients with SPN in the context of chemotherapy treatment with oxaliplatin for colon cancer were instructed to express through an electronic VAS system (eVAS); the level of sensation felt when a thermode set at either 39º, 41º, 43º, 45º or 47º was applied to their ventral forearm. Results The eVAS recordings showed typically an abrupt onset that slowed to approach maximum sensation and continued with a slow decrease indicating adaptation. The time to respond (TR), the velocity of the initial response (VR), the maximum sensation (MA), the time to reach MA (MAt), the onset of adaptation (AO) and the decrease in the sensation level with respect to MA at 30 s after stimulus application (SL30), were dependent on the temperature level in all subjects. However, patients showed significantly delayed TR, slowed VR, decreased MA, delayed AO and reduced SL30, with respect to healthy subjects. Differences were more pronounced at low-temperature levels, with absent AO in 25 patients versus 2 healthy subjects at temperatures of 39º and 41ºC. Conclusion The study of adaptation to a constant temperature stimulus can furnish valuable data for the assessment of patients with SPN. SIGNIFICANCE: We studied perceptual changes in the intensity of thermoalgesic sensation during 30 s of constant temperature stimulation after an abrupt initial contact in healthy subjects and patients with sensory polyneuropathy. Patients showed delayed time to respond, decreased maximal sensation and reduced adaptation with respect to healthy subjects. Differences were more pronounced at low and intermediate temperatures (39ºC to 43ºC). The method is of easy implementation and shows clinically relevant abnormalities in patients with sensory polyneuropathy.

Prognostic value of cutaneous reinnervation with GAP-43 in oxaliplatin-induced neuropathy.

BACKGROUND AND PURPOSE: Oxaliplatin-induced neuropathy (OIN) implies axonal damage of both small and large sensory nerve fibers. We aimed at comparing the neurophysiological changes occurred after treatment and the capability to recovery based on histological marker of re-innervation GAP-43. METHODS: 48 patients with cancer were assessed before and after chemotherapy (at 3 months and 12 months if available). We recorded ulnar and sural sensory nerve action potentials (SNAP), determined quantitative sensory thresholds for warm and cold (WDT, CDT), pain thresholds and collected a distal biopsy of skin to assess the intra-epidermal nerve fiber density (IENFD) with PGP9.5 and GAP-43 markers (in a subgroup of 19 patients). RESULTS: Increased WDT and CDT as well as diminished IENFD at distal leg were already found in 30% of oncologic patients before treatment. After oxaliplatin, there was a significant increase in thermal thresholds in 52% of patients, and a decrease of SNAP amplitude in the sural nerve in 67% patients. IENFD was reduced in 47% and remained unchanged in 37% after oxiplatin. The density of GAP-43 + fibers and GAP-43/PGP 9.5 ratio was similar before and after treatment showing that cutaneous re-innervation is preserved despite no clinical recovery was observed after one year. CONCLUSION: Non-selective axonal loss affects sensory fibers in OIN. However, the presence of intra-epidermal regenerative sprouts detected by GAP-43 may reduce the impact of neurotoxicity in the small fibers with long-term sequelae mostly on myelinated nerve endings. Pre-oxaliplatin GAP-43 failed to identify patients with higher risk of damage or worse recovery after treatment.

The somatosensory blink reflex in upper and lower brainstem lesions.

The brainstem pathways that mediate the somatosensory blink reflex (SBR) are not completely understood. We hypothesized that the circuits of the SBR might be affected separately from those of the trigeminal blink reflex (TBR). We examined 7 patients with mesencephalic lesions and 8 patients with medullary lesions. The SBR was elicited by median nerve stimulation. The TBR was elicited by supraorbital nerve stimulation. In patients with upper brainstem lesions, the TBR was normal, whereas the SBR was generally abnormal. The SBR was either absent or small and was significantly delayed with respect to control subjects. The opposite was the rule in patients with lower brainstem lesions who had delayed or absent TBR and no abnormal findings in the SBR. The SBR is mediated through circuits in the upper brainstem. Study of the SBR can be helpful in the neurophysiological assessment of patients with mesencephalic lesions.

Reinnervation by the contralateral facial nerve in patients with peripheral facial palsy.

INTRODUCTION: Reinnervation activity is triggered after complete unilateral peripheral facial palsy (PFP). METHODS: In 27 patients with PFP we recorded electromyographic activity with a concentric needle electrode inserted 1 cm lateral to the oral commissure of the affected side. We applied electrical stimuli to the unaffected (contralateral) facial nerve from the tragus to the mid-lower lip and measured the response latency variability and segmental conduction velocity. RESULTS: Responses to electrical stimulation of the unaffected facial nerve were found in all patients. Mean conduction velocity was 49.6 ± 6.2 m/s between tragus and oral commissure, and 6.0 ± 1.9 m/s between oral commissure and mid-lower lip. Latency variability was 0.27 ms to facial nerve stimulation and 0.08 ms to oral commissure stimulation. CONCLUSION: Short distance sprouting of axons that innervate muscle fibers, which originate from the unaffected facial nerve, results in propagation of impulses to muscle fibers in the midline.

Modulation of the soleus H reflex by electrical subcortical stimuli in humans.

Over the past two decades, the H reflex has been used as a neural tool to assess the effect on the motoneuronal pool of conditioning volleys in supraspinal descending tracts elicited by transcranial magnetic stimulation (TMS) or auditory stimuli. However, mechanisms mediating such modulation are unclear. These hypothesized neural pathways are likely to be affected by single electrical stimulus applied through the electrodes implanted in the subthalamic nucleus for deep brain stimulation (sSTNDBS). To improve our knowledge on such mechanisms, we examined in 11 Parkinson's disease patients the effects of conditioning sSTNDBS applied contralateral and ipsilateral to the H reflex recording on the amplitude of the soleus H reflex, at interstimulus intervals (ISIs) between 0 and 110 ms. There was a significant main effect of the ISI (P<0.001) and of the sSTNDBS stimulation side (P=0.019) on the percentage change in the soleus H-reflex amplitude. Contralateral sSTNDBS modulation of the soleus H reflex resembles that of TMS in healthy subjects with two facilitation phases (at 5-20 ms and at 60 ms), while after ipsilateral sSTNDBS, there is only a single facilitation phase peaking up at 5 ms later than the first facilitation period observed with contralateral stimulation. These findings contribute to the discussion of the mechanisms underlying the excitability of the spinal alpha motoneuron pool and the modulation of the H reflex by supraspinal stimuli.

Electrodiagnostic Testing of Small Fiber Neuropathies: A Review of Existing Guidelines.

This article reviews the literature on neurophysiological techniques for the diagnosis of small fiber neuropathy. The review is focused on clinical approach to suspected small fiber neuropathy, letting aside techniques whose clinical applicability is doubtful. We include, however, the special techniques required to examine C and Aδ fibers, which cannot be evaluated directly with conventional neurophysiological methods. The most relevant publications are summarized and recommendations for the clinical assessment of small fiber neuropathy are provided.

Excessive muscle activity increases over time in idiopathic REM sleep behavior disorder.

STUDY OBJECTIVES: Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by excessive electromyographic (EMG) activity due to dysfunction of the brainstem structures modulating REM sleep atonia. Patients with idiopathic RBD often develop a neurodegenerative disease, such as Parkinson disease, over the years, suggesting progression of an underlying pathologic process in the brainstem. It is unknown if the excessive EMG activity in REM sleep changes over time in patients with idiopathic RBD. SETTING: University hospital sleep disorders center. PARTICIPANTS: Eleven patients with idiopathic RBD who were studied at baseline and after a mean follow-up of 5 years. INTERVENTIONS: NA. MEASUREMENTS AND RESULTS: Eleven patients with idiopathic RBD underwent polysomnography (PSG) at the moment of the diagnosis of RBD (PSG1) and after a mean follow-up of 5 years (PSG2). Tonic EMG activity in PSG1 and PSG2 was blindly quantified and compared in the mentalis muscle during REM sleep. Phasic EMG activity in PSG1 and PSG2 was blindly quantified and compared in the mentalis muscle, both biceps brachii, and both anterior tibialis during REM sleep. Patients were 9 men and 2 women with a mean age of 73.2 +/- 5.4 years and a mean RBD duration of 10.7 +/- 5.3 years at PSG2. In each of the 5 muscles and combination of muscles evaluated, phasic EMG activity was significantly greater in PSG2 than in PSG1 (P < 0.022 in all muscles studied). Mentalis tonic EMG activity increased from 30% to 54% (P = 0.013). No correlation was found between age of the patients and quantity of EMG activity at PSG1 (tonic; P = 0.69, phasic P = 0.89) and at PSG2 (tonic; P = 0.16, phasic; P = 0.42). CONCLUSION: Excessive tonic and phasic EMG activity during REM sleep increases over time in subjects with idiopathic RBD. This finding suggests that, in subjects with idiopathic RBD, there is an underlying progressive pathologic process damaging the brainstem structures that modulate REM sleep.

Acute lumbar polyradiculoneuropathy as early sign of methotrexate intrathecal neurotoxicity: Case report and literature review.

Acute paraplegia after treatment with intrathecal methotrexate requires a complete spinal cord neuroimaging as well as electrodiagnostic examination. The absence of lumbosacral F waves motor responses without demyelinating findings may indicate early direct root toxicity. Early electromyography (EMG) screening could be a valuable tool for detecting peripheral neurotoxicity.