Rasch‐Transformed Total Neuropathy Score clinical version (RT‐TNSc©) in patients with chemotherapy‐induced peripheral neuropathy

Composite scales such as the Total Neuropathy Score clinical version (TNSc^©) have been widely used to measure neurological impairment in a standardized manner but they have been criticized due to their ordinal setting having no fixed unit. This study aims to improve impairment assessment in patients with chemotherapy‐induced peripheral neuropathy (CIPN) by subjecting TNSc^© records to Rasch analyses. In particular, we wanted to investigate the influence of factors affecting the use of the TNSc^© in clinical practice. TNSc^© has 7 domains (sensory, motor, autonomic, pin‐prick, vibration, strength, and deep tendon reflexes [DTR]) each being scored 0–4. Data obtained in 281 patients with stable CIPN were subjected to Rasch analyses to determine the fit to the model. The TNSc^© did not meet Rasch model's expectations primarily because of misfit statistics in autonomic and DTR domains. Removing these two, acceptable model fit and uni‐dimensionality were obtained. However, disordered thresholds (vibration and strength) and item bias (mainly cultural) were still seen, but these findings were kept to balance the assessment range of the Rasch‐Transformed TNSc^© (RT‐TNSc^©). Acceptable reliability findings were also obtained. A 5‐domains RT‐TNSc^© may be a more proper assessment tool in patients with CIPN. Future studies are needed to examine its responsive properties.     

Association of electrochemical skin conductance with neuropathy in chemotherapy-treated patients

Purpose

Chemotherapy-induced peripheral neuropathy (CIPN) is an adverse event of cancer treatment that can affect sensory, motor, or autonomic nerves. Assessment of autonomic neuropathy is challenging, with limited available tools. Accordingly, it is not routinely assessed in chemotherapy-treated patients. In this study, we aimed to examine whether electrochemical skin conductance (ESC) via Sudoscan, a potential measure of autonomic function, associates with subjective and objective measures of CIPN severity and autonomic neuropathy.

Methods

A cross-sectional assessment of patients who completed neurotoxic chemotherapy 3–24 months prior was undertaken using CIPN patient-reported outcomes (EORTC-QLQ-CIPN20), clinically graded scale (NCI-CTCAE), neurological examination score (TNSc), autonomic outcome measure (SAS), and Sudoscan. Differences in CIPN severity between participants with or without ESC dysfunction were investigated. Linear regression analyses were used to identify whether ESC values could predict CIPN severity.

Results

A total of 130 participants were assessed, with 93 participants classified with CIPN according to the clinically graded scale (NCI-CTCAE/grade ≥ 1), while 49% demonstrated hands or feet ESC dysfunction (n = 46). Participants with ESC dysfunction did not significantly differ from those with no dysfunction on multiple CIPN severity measures (clinical-grade, patient-report, neurological examination), and no differences on the autonomic outcome measure (SAS) (all p > 0.0063). Linear regression analyses showed that CIPN could not be predicted by ESC values.

Conclusions

The inability of ESC values via Sudoscan to predict clinically-graded and patient-reported CIPN or autonomic dysfunction questions its clinical utility for chemotherapy-treated patients. The understanding of autonomic neuropathy with chemotherapy treatment remains limited and must be addressed to improve quality of life in cancer survivors.

     

Olfactory performance in spinocerebellar ataxia type 7 patients

A large body of evidence has shown olfactory deficits in many neurodegenerative diseases. However, the nature of the olfactory impairment remains poorly understood partly because the majority of studies have only explored smell identification capabilities. The purpose of the present study was twofold. First we wanted to test if patients with spinocerebellar ataxia type 7 (SCA7), a progressive neurodegenerative disorder characterized by cerebellar ataxia and visual loss, also have olfactory deficits. Secondly, we wanted to test the nature of the olfactory deficits by testing not only the identification level but also olfactory threshold and discrimination. Based on the olfactory dysfunction found in different neurodegenerative diseases and functional neuroimaging data showing cerebellar activation during olfaction, we hypothesized that SCA7 patients would show an olfactory impairment. To test this hypothesis we studied twenty-eight genetically confirmed SCA7 patients and twenty-seven matched controls using the Sniffing Sticks Test and the University of Pennsylvania Smell Identification Test (UPSIT). The results show that SCA7 patients' ability to discriminate and identify odors is significantly impaired, although their odor detection thresholds were at normal levels. These results suggest that SCA7 neurological damage affects olfactory perception but spares the patients' olfactory sensory capabilities.     

Chemotherapy-induced peripheral neurotoxicity can be misdiagnosed by the National Cancer Institute Common Toxicity scale

The assessment of chemotherapy-induced peripheral neurotoxicity (CIPN) is still uncertain as several of the most frequently used scales do not rely on a formal neurological evaluation and depend on patients' reports and examiners' interpretations. The aim of this study was to compare the assessment of CIPN using the National Cancer Institute Common Toxicity Criteria (NCI-CTC) scale and a formal neurological assessment scored with the Total Neuropathy Score (TNS, i.e., a composite scale designed to grade the impairment in neuropathy patients) to identify possible discrepancies in the diagnosis. In this prospective study, 155 patients treated with cisplatin/carboplatin or with paclitaxel/docetaxel and CIPN were examined in a collaborative oncological/neurological multi-center trial using the NCI-CTC scale and the TNS; the results were then extensively compared. We evidenced that the TNS allows possible misdiagnosed neuropathies to be revealed. In fact, the NCI-CTC evaluation performed by experienced examiners overestimated the occurrence of motor neuropathy, possibly because of the presence of confounding factors (e.g., fatigue, depression, cachexia), which might be difficult to be ruled out without a formal neurological examination. This study strongly indicates that a more formal neurological assessment of patients with CIPN than that achievable with the common toxicity scales (e.g., NCI-CTC) is advisable.     

Sensory sensitivity to external stimuli in Tourette syndrome patients

Patients with Tourette Syndrome often state that their sensitivity to sensations is equally or more disruptive than are motor tics. However, their sensory sensitivity is not addressed by standard clinical assessments nor is it a focus of research. This lapse likely results from our limited awareness and understanding of the symptom. In this study (1) we defined the patients' experience of sensitivity to external stimuli in detail, and (2) we tested 2 hypotheses regarding its origin. First, we interviewed in depth and administered a lengthy questionnaire to adult Tourette patients (n = 19) and age‐matched healthy volunteers (n = 19). Eighty percent of patients described heightened sensitivity to external stimuli, with examples among all 5 sensory modalities. Bothersome stimuli were characterized as faint, repetitive or constant, and nonsalient, whereas intense stimuli were well tolerated. We then determined whether the sensitivity could be the result of an increased ability to detect faint stimuli. After measuring the threshold of detection for olfactory and tactile stimuli among the patients and healthy volunteers, we found no significant differences between them for either sensory modality. These results indicate that patients' perceived sensitivity derives from altered central processing rather than enhanced peripheral detection. Last, we assessed one aspect of processing: the perception of intensity. When subjects rated the intensity of near‐threshold tactile and olfactory stimuli, there was a surprising difference: Tourette patients more frequently used the lowest range of the scale than did healthy volunteers. Future research is necessary to define the anatomical and physiological basis of the patients' experience of heightened sensitivity. © 2011 Movement Disorder Society     

Sensory perception changes induced by transcranial magnetic stimulation over the primary somatosensory cortex in Parkinson's disease

Sensory symptoms are common nonmotor manifestations of Parkinson's disease. It has been hypothesized that abnormal central processing of sensory signals occurs in Parkinson's disease and is related to dopaminergic treatment. The objective of this study was to investigate the alterations in sensory perception induced by transcranial magnetic stimulation of the primary somatosensory cortex in patients with Parkinson's disease and the modulatory effects of dopaminergic treatment. Fourteen patients with Parkinson's disease with and without dopaminergic treatment and 13 control subjects were included. Twenty milliseconds after peripheral electrical tactile stimuli in the contralateral thumb, paired‐pulse transcranial magnetic stimulation over the right primary somatosensory cortex was delivered. We evaluated the perception of peripheral electrical tactile stimuli at 2 conditioning stimulus intensities, set at 70% and 90% of the right resting motor threshold, using different interstimulus intervals. At 70% of the resting motor threshold, paired‐pulse transcranial magnetic stimulation over the right primary somatosensory cortex induced an increase in positive responses at short interstimulus intervals (1–7 ms) in controls but not in patients with dopaminergic treatment. At 90% of the resting motor threshold, controls and patients showed similar transcranial magnetic stimulation effects. Changes in peripheral electrical tactile stimuli perception after paired‐pulse transcranial magnetic stimulation over the primary somatosensory cortex are altered in patients with Parkinson's disease with dopaminergic treatment compared with controls. These findings suggest that primary somatosensory cortex excitability could be involved in changes in somatosensory integration in Parkinson's disease with dopaminergic treatment. © 2011 Movement Disorder Society     

Functioning of patients with multifocal motor neuropathy

Patients with multifocal motor neuropathy (MMN) have slowly progressive, predominantly distal asymmetric limb weakness without sensory loss. While previous studies have investigated the impact of MMN on body functions and structures, relatively little is known about the impact of patients' weakness on daily functioning. The aim of the present cross‐sectional study, involving 47 patients with MMN, was to evaluate determinants of patients' functioning. Most patients showed not only muscle weakness but also fatigue, limited dexterity, and limited walking ability. Regression models showed that age, hand aids, and muscle strength scores together explained 54% of the variance in dexterity scores, which in turn explained 8% of the variance in patients' scores for autonomy indoors. Age, the use of walking aids, and muscle strength scores together explained 58% of the variance in walking ability scores, which in turn explained 18% of the variance in patients' scores for autonomy indoors and 7% of the variance in patients' scores for autonomy outdoors. Assessment of determinants of patient functioning may make it possible to tailor interventions to address these aspects and thereby improve patients' functioning in daily life.     

Chemotherapy‐induced peripheral neuropathy: A current review

Chemotherapy‐induced peripheral neuropathy (CIPN) is a common dose‐limiting side effect experienced by patients receiving treatment for cancer. Approximately 30 to 40% of patients treated with neurotoxic chemotherapy will develop CIPN, and there is considerable variability in its severity between patients. It is often sensory‐predominant with pain and can lead to long‐term morbidity in survivors. The prevalence and burden of CIPN late effects will likely increase as cancer survival rates continue to improve. In this review, we discuss the approach to peripheral neuropathy in patients with cancer and address the clinical phenotypes and pathomechanisms of specific neurotoxic chemotherapeutic agents. Ann Neurol 2017;81:772–781     

When is sensorimotor stroke a lacunar syndrome?

Forty five patients with clear sensorium and no neurological deficits other than unilateral motor and sensory impairment underwent computed tomography (CT). Twenty patients had sensorimotor stroke with impairment of all sensory modalities (type 1). Eight had only impairment of nociceptive sensation (type 2) and 15 had only proprioceptive impairment (type 3). Two patients had sensory impairment in one limb only (type 4). Lacunes were found in patients in the first three groups. However, 80% of those who had hemiparesis and incomplete sensory loss were found to have a lacune or normal CT scan whilst only 33% of those with complete motor or sensory impairment had lacunes. It is proposed that sensorimotor stroke as a lacunar syndrome be best restricted to those with only mild to moderate hemiparesis and sensory impairment in both upper and lower limbs. The degree and extent of sensory and motor involvement may vary, however, possibly dependent on whether the thalamo-geniculate, anterior choroidal or lateral lenticulostriate artery is affected.     

Multi-center assessment of the Total Neuropathy Score for chemotherapy-induced peripheral neurotoxicity

The aim of this multi-center study was to assess with reduced versions of the Total Neuropathy Score (TNS), the severity of chemotherapy-induced peripheral neurotoxicity (CIPN), and to compare the results with those obtained with common toxicity scales. An unselected population of 428 cancer patients was evaluated at 11 different centers using a composite (clinical + neurophysiological, TNSr) or clinical (TNSc) examination and with the National Cancer Institute - Common Toxicity Criteria (NCI-CTC) 2.0 and Eastern Cooperative Oncology Group (ECOG) scores. A highly significant correlation was demonstrated between the TNSr and the NCI-CTC 2.0 and ECOG scores; but the TNSr evaluation was more accurate in view of the more extended score range. Also, the simpler and faster TNSc (based only on the clinical neurological examination) allowed to grade accurately CIPN and correlated with the common toxicity scores. The correlation tended to be closer when the sensory items were considered, but also the TNSr motor items, which were not specifically investigated in any other previous study, significantly correlated with the results of the common toxicity scales. In conclusion, this study suggests that the TNSr is a reliable tool for accurately grading and reporting CIPN, with the additional and so far unique support of a formal comparison with known and widely used common toxicity scales. The TNSc is a valid alternative if neurophysiological examination is not feasible. The longer time needed to calculate the TNSr and TNSc in comparison to the ECOG or the NCI-CTC 2.0 scales is offset by the more detailed knowledge of the CIPN characteristics.     

Chemotherapy‐induced peripheral neurotoxicity: A multifaceted,still unsolved issue

Chemotherapy‐induced peripheral neurotoxicity (CIPN) is a potentially dose‐limiting side effect of several commonly used cytotoxic chemotherapy agents. The main pharmacological classes that may cause CIPN include classical anticancer drugs, as well as the recently introduced immune checkpoint inhibitors and antibody drug conjugates. The absence of a complete knowledge of CIPN pathophysiology is only one of the several unsolved issues related to CIPN. Among some of the most relevant aspects of CIPN deserving further attention include the real number of patients exposed to the risk of CIPN, the long‐term impact on cancer survivors' quality of life due to incomplete recovery from CIPN, the economic burden related to acute and chronic CIPN, and the different perspective and education of the healthcare specialists in charge of managing patients with CIPN. Overall, CIPN remains a very challenging area of research as there are still several unresolved issues to be addressed in the future. In this special issue, the multifaceted profile of CIPN will be presented, with particular emphasis on bolstering the need to develop more optimized outcome measures than the existing ones to accurately evaluate the extent of CIPN, but also to ascertain the differences in the incidence, risk factors, clinical phenotype, and management of CIPN, according to the most commonly used neurotoxic chemotherapy classes. Perspectives for future research to pursue in order to cover the gaps in knowledge in the CIPN field will also be discussed.     

Electrophysiological features of the mouse tail nerves and their changes in chemotherapy induced peripheral neuropathy (CIPN)

Electrophysiology of tail nerves in rodents has been demonstrated a reliable method to investigate models of peripheral neuropathies. Nevertheless, data concerning mouse models are lacking. We assessed the normal features of sensory and motor conduction of tail nerves in adult mice. We found that, as in rats, a sensory compound action potential and motor responses could be recorded with the non invasive and highly reliable technique proposed, especially if bipolar derivations were used. We also investigated the changes related to chemotherapy induced peripheral neuropathy (CIPN) after paclitaxel treatment (times 1 and 2), compared to pre-treatment (time 0) and to controls. It was found that only the sensory compound action potential was involved in CIPN, with decrease in amplitude and conduction velocity, suggesting a significant reduction in number of fast conducting fibres and a correspondent increase in the number of slow conducting ones, although the total amount of active myelinated fibres was deemed to be unchanged through time 0, time 1 and time 2. The results obtained in CIPN provide new functional evidence about the involvement of sensory fibres and may help in better understanding the underlying mechanisms.     

Health‐related quality of life in multiple system atrophy

Although multiple system atrophy (MSA) is a neurodegenerative disorder leading to progressive disability and decreased life expectancy, little is known about patients' own evaluation of their illness and factors associated with poor health‐related quality of life (Hr‐QoL). We, therefore, assessed Hr‐QoL and its determinants in MSA. The following scales were applied to 115 patients in the European MSA‐Study Group (EMSA‐SG) Natural History Study: Medical Outcome Study Short Form (SF‐36), EQ‐5D, Beck Depression Inventory (BDI), Mini‐Mental state examination (MMSE), Unified MSA Rating Scale (UMSARS), Hoehn & Yahr (H&Y) Parkinson's disease staging scale, Composite Autonomic Symptom Scale (COMPASS), and Parkinson's Disease Sleep Scale (PDSS). Forty‐six percent of patients had moderate to severe depression (BDI ≥ 17); Hr‐QoL scores on the SF‐36 and EQ‐5D were significantly impaired. Pain, the only domain with similar scores in MSA and published PD patients, was reported more frequently in patients with MSA‐P (predominantly parkinsonian motor subtype) than MSA‐C (predominantly cerebellar motor subtype; 76% vs. 50%; P = 0.005). Hr‐QoL scores correlated most strongly with UMSARS motor, COMPASS, and BDI scores but not with MMSE scores, age at onset, or disease duration. The COMPASS and UMSARS activities of daily living scores were moderate‐to‐strong predictors for the SF‐36 physical summary score and the BDI and UMSARS motor scores for the SF‐36 mental summary score. This report is the first study to show that Hr‐QoL is significantly impaired in MSA. Although not all possible factors related to impaired Hr‐QoL in MSA could be assessed, autonomic dysfunction, motor impairment, and depression were most closely associated with poor Hr‐QoL, and therapeutic management, therefore, should concentrate upon these aspects of the disease. © 2006 Movement Disorder Society     

Axonal sensory motor neuropathy in copper‐deficient Wilson's disease

Copper deficiency may cause myeloneuropathy or progressive limb weakness. By contrast, Wilson's disease (WD) is characterized by progressive copper accumulation with hepatic and neurological impairment and requires life‐long treatment with zinc and/or chelator agents. We report a WD patient who developed axonal sensory motor neuropathy in the context of copper deficiency due to his treatment with zinc and chelators. Exhaustive testing for other etiologies was negative. After treatment adjustment, only mild clinical improvement was noted during long‐term follow‐up. Muscle Nerve 40: 294–296, 2009     

The modified rankin scale to assess disability in myasthenia gravis: Comparing with other tools

Introduction: We explored the modified Rankin scale (mRS) as a tool to quantitate disability in myasthenia gravis (MG). Our aim was to correlate patients' perception of their disability with that of the care provider and determine its relationship with other MG‐related scores. Methods: We evaluated 107 MG patients at 2 neurological centers. Patients were assessed over the telephone before and after clinic visits using the 15‐item Myasthenia Gravis Quality‐of‐Life index (MG‐QOL15) and mRS. At the clinic, patients were assessed using the MG‐QOL15, MG Composite (MGC), and mRS. Results: The MG‐QOL15 correlated with the MGC, mRS, and assessors' scores of patients. Assessors' perception of disease burden was in line with that of the patients' scoring. MG‐QOL15 scores obtained over the telephone were consistent with those obtained in the clinic. Scores were generally higher in patients receiving steroids at >5 mg/day and in those receiving or seeking benefits. Conclusion: The MG‐QOL15 and mRS are useful for estimating disability in MG. Muscle Nerve 50 : 501–507, 2014     

Electrophysiological and phenotypic profiles of taxane-induced neuropathy

ObjectiveTo comprehensively describe patient-reported, functional and neurophysiological outcomes to elucidate the phenotypic profile of taxane-induced neuropathy.MethodsTaxane-treated patients (n = 47) completed cross-sectional bilateral clinical and sensory assessments and nerve conduction studies. Patients reported symptom severity via Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx13) questionnaire.ResultsSymptoms of neuropathy were reported by 81% of patients. On clinical examination, 62% had 2 or more abnormalities, with 20% indicating significant symptomatic and objective neuropathy. Nerve conduction studies were consistent with a sensory predominant axonal neuropathy. However, features more typical of entrapment neuropathy were also present in > 50%, which were not associated with overall severity of chemotherapy-induced peripheral neuropathy (CIPN) or clinical risk factors.ConclusionsThere is considerable variation in CIPN phenotypes associated with taxane-treatment. Understanding their clinical associations may assist in identification of patients at risk of severe neurotoxicity. This would enable treatment modification decisions but also limit early cessation of effective anti-cancer treatment in patients with less severe neurological sequelae.SignificanceUnderstanding the CIPN phenotype may inform treatment decisions which could impact clinical and survival outcomes.     

Psychosis in Parkinson's disease without dementia: Common and comorbid with other non‐motor symptoms

Psychosis in Parkinson's disease (PD) is common and associated with a range of negative outcomes. Dementia and psychosis are highly correlated in PD, but the frequency and correlates of psychosis in patients without cognitive impairment are not well understood. One hundred and ninety‐one non‐demented PD patients at two movement disorders centers participated in a study of neuropsychiatric complications in PD and completed a detailed neurological and neuropsychiatric assessment, including the rater‐administered Parkinson Psychosis Rating Scale for hallucinations, delusions, and minor symptoms of psychosis (illusions and misidentification of persons). Psychotic symptoms were present in 21.5% of the sample. Visual hallucinations were most common (13.6%), followed by auditory hallucinations (6.8%), illusions or misidentification of people (7.3%), and paranoid ideation (4.7%). Visual hallucinations and illusions or misidentification of people were the most common comorbid symptoms (3.1%). Depression (P = 0.01) and rapid eye movement behavior disorder symptoms (P = 0.03) were associated with psychosis in a multivariable model. The odds of experiencing psychotic symptoms were approximately five times higher in patients with comorbid disorders of depression and sleep‐wakefulness. Even in patients without global cognitive impairment, psychosis in PD is common and most highly correlated with other non‐motor symptoms. Screening for psychosis should occur at all stages of PD as part of a broad non‐motor assessment. In addition, these findings suggest a common neural substrate for disturbances of perception, mood, sleep‐wakefulness, and incipient cognitive decline in PD. © 2012 Movement Disorder Society     

The prediction of stress in carers: The role of behaviour,reported self care and dementia in patients with idiopathic Parkinson's disease

Stress scores were elicited from relatives living with Parkinsonian patients and correlated with various aspects of the patients' impairment. The (usually female) relatives looking after male patients reported higher levels of stress than husbands looking after their wives. In general, the best predictor of relatives' stress was the behavioural rating scale of the CAPE and a reported selfcare scale designed for the study. The relative contribution of Parkinsonian motor impairment and cognitive impairment to relatives' stress scores was examined. While motor impairment was still associated with relatives' stress after controlling for sex and cognitive deterioration, both dementia and cognitive impairment measured by the Mini-Mental State Examination were not associated with relatives' stress if Parkinsonian disability was controlled for.     

Neuropathy and cognitive impairment following vaccination with the OspA protein of Borrelia burgdorferi

Neurological syndromes that follow vaccination or infection are often attributed to autoimmune mechanisms. We report six patients who developed neuropathy or cognitive impairment, within several days to 2 months, following vaccination with the OspA antigen of Borrelia burgdorferi. Two of the patients developed cognitive impairment, one chronic inflammatory demyelinating polyneuropathy (CIDP), one multifocal motor neuropathy, one both cognitive impairment and CIDP, and one cognitive impairment and sensory axonal neuropathy. The patients with cognitive impairment had T2 hyperintense white matter lesions on magnetic resonance imaging. The similarity between the neurological sequelae observed in the OspA-vaccinated patients and those with chronic Lyme disease suggests a possible role for immune mechanisms in some of the manifestations of chronic Lyme disease that are resistant to antibiotic treatment.     

Abnormal vibration‐induced illusion of movement in idiopathic focal dystonia: An endophenotypic marker?

The frequency of symptomatic dystonia in relatives of patients with idiopathic focal dystonia (IFD) is higher than expected from epidemiologic studies implying that genetic factors may be involved. Perception of the vibration‐induced illusion of movement (VIIM) is subnormal in patients with IFD compared with healthy volunteers and the abnormality corrects with volitional fatigue of the vibrated arm. The aim of the study was to establish the heritability of the abnormality of VIIM. The perception of illusion of movement elicited by vibration of the biceps brachii tendon before and after fatigue of the muscles was investigated in 30 patients with torticollis, 57 of their first degree relatives, and 19 healthy volunteers. VIIM did not change after fatigue in healthy controls. Before fatiguing the muscles, patients' perception of VIIM was less than healthy controls, (P < 0.01, unpaired t‐test). After fatigue, the illusion of movement perceived by patients increased, so that it did not differ any more from that of the healthy control subjects (P < 0.05, repeated measures ANOVA). First degree relatives' response to vibration varied; 45% of parents, 60.7% of siblings, and 63.6% of children had an “abnormal” response to vibration compared with 21% of healthy volunteers. In contrast to patients' response, the “abnormality” did not correct after volitional fatigue of the vibrated arm. The results suggest that abnormal VIIM may represent an endophenotypic marker for IFD, which interacts with other factors including central motor learning and compensation mechanisms in the expression of the dystonic phenotype. © 2007 Movement Disorder Society