Central nervous system involvement in patients with monoclonal gammopathy and polyneuropathy

Background and purpose: To evaluate clinical presentation of patients with the clinical triad of monoclonal gammopathy, polyneuropathy and signs of CNS involvement. Methods: Nineteen patients with monoclonal protein (M‐protein, 9 IgM, 10 IgG) were studied. Clinical examination, MRI, cerebrospinal fluid analysis and immune reactivity against myelin‐associated glycoprotein and gangliosides in serum were obtained. By immunohistochemistry, different binding patterns of M‐proteins to human CNS tissue were investigated. Results: Nine out of 19 patients (four IgM, five IgG) showed one or more clinical signs of CNS involvement. Clinical features associated with signs of CNS pathology were disease duration and greater concentration of IgM paraprotein. The IgM M‐protein of two patients strongly stained the cortex/cerebellar neurons in human brain sections. Conclusion: Our results complement previous reports that some patients with monoclonal gammopathy and polyneuropathy can develop solitary or disseminated signs of CNS involvement. It indicates that pathological effects of M‐proteins are not necessarily restricted to the peripheral nervous system. The specificity and affinity of circulating M‐protein to antigens in the CNS might be critical for the development of different clinical phenotypes.     

Impact of electromyographic findings on choice of treatment and outcome1

The subsequent clinical course of patients examined in the EMG laboratory has not been adequately studied before. It is not known how EMG findings in practice affect patients’ final diagnosis, treatment and outcome. The aim of the present study was to test the hypothesis that EMG results have an important impact on the choice of patients’ treatment and on outcome. Three years after EMG examination, a short questionnaire asking about initial symptoms, the final diagnosis, treatment and current symptoms was sent to 300 consecutive EMG patients. Responses concerning 186 of them (39% men) were received either from patients and/or from their referring physicians. Information obtained during EMG examination was also added. Data was analyzed using methods of bivariate and multivariate statistics. We found that patients with a pathologic EMG had a better clinical outcome 3 years later. Pathologic EMG has an independent effect, pointing to more favorable disease courses, which was further improved by more active treatment approaches received by these patients. The study demonstrated the important impact of EMG findings on the treatment choice and clinical outcome in population consisting mainly of patients with carpal tunnel syndrome and radiculopathy. Studies in other patient populations are needed.     

Diagnosis of diabetic polyneuropathy Correlation between clinical and instrumental findings and assessment of simple diagnostic criteria

In the present study minimal clinical and electrophysiological criteria for the diagnosis of diabetic polyneuropathy (DP) have been tested in 48 unselected subjects attending an outpatient service for diabetics at the University Hospital of Chieti. A standard electrophysiological examination was performed in all patients on the median nerve (sensory and motor), peroneal nerve and sural nerve. Depending on the importance of the laboratory values for each nerve, nerve conduction velocity, distal latency and potential amplitude were given separate scores ranging from 0.5 to 2. A diagnosis of probable DP was made when abnormal findings were present in more than one nerve with a total score of 2.5 or more. As a whole, 28 cases (58%) had abnormal laboratory findings supporting the diagnosis of probable DP. There was a relatively high correlation between probable DP and a positive clinical examination although the validity coefficients of the neurological exam were not high enough to allow its use as a screening test for DP.

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Sommario Nella presente indagine alcuni criteri clinici ed elettrofisiologici di minima per la diagnosi di polineuropatia diabetica (PD) sono stati scelti e testati su di un campione non selezionato di 48 soggetti afferenti all'Ambulatorio di Diabetologia dell'Ospedale Universitario di Chieti. Su ciascun paziente è stato eseguito un esame strumentale standard a carico dei nervi mediano (sensitivo e motore), peroneo e surale. Con riferimento alla relativa importanza dei parametri strumentali per ciascun nervo, a velocità di conduzione, latenza distale ed ampiezza dei potenziali furono attribuiti punteggi che variavano da 0,5 a 2. Veniva formulata una diagnosi di probabile PD quando il punteggio totale su almeno due nervi era di 2,5 o più. Sul totale, 28 casi (58%) avevano un quadro strumentale a sostegno della diagnosi di probabile PD. Per quanto vi fosse una correlazione relativamente alta tra positività dell'esame clinico e diagnosi di probabile PD, i coefficienti di validità dell'esame neurologico non risultavano sufficientemente elevati da consentirne l'impiego per lo screening della PD.

     

Hospital-referred polyneuropathies-causes, prevalences, clinical- and neurophysiological findings

The aim of this study was to evaluate the causes, prevalences, clinical manifestations of hospital-referred polyneuropathies, and evaluate neurophysiological findings in idiopathic polyneuropathy. From 2000 to 2005, 226 patients with polyneuropathy were examined. Polyneuropathy was diagnosed when symptoms, clinical- and neurophysiological findings were compatible with affection of at least two peripheral nerves. They were classified in symptomatic and idiopathic polyneuropathy after investigation. Clinical manifestations were evaluated for diabetes- (DPN), inflammatory- (INPN), hereditary- (HPN) and idiopathic polyneuropathy (IDPN). Neurophysiological findings were investigated in IDPN. 72% had a symptomatic polyneuropathy. Most frequent causes were diabetes mellitus (18%), inflammation, (16%) and hereditary (14%). Most common prevalences per 100 000 were as follows: IDPN, 21; DPN, 13 and HPN, 11. Predominating clinical manifestations were: sensory and motor in INPN, HPN and IPN; sensory in DPN. Pain was more present in IDPN and DPN than in others. In IDPN axonal demyelinating affection was present in 20%. Symptomatic polyneuropathy was common and diabetes mellitus, inflammation and hereditary were frequent causes. In IDPN, DPN, HPN and INPN different clinical patterns were found. Additionally, in IDPN axonal demyelinating affection was more frequent than previously reported.     

Correlation between clinical/neurophysiological findings and quality of life in Charcot-Marie-Tooth type 1A

Abstract   Quality of life (QoL), as defined by the Short Form 36, has previously been shown to be abnormal in patients with Charcot-Marie-Tooth disease (CMT), both for Physical Composite Scores (PCS) and Mental Composite Scores (MCS). We have now extended these observations in a multicenter evaluation of 89 patients with Charcot-Marie-Tooth disease type 1A, the most common form of CMT. Both the PCS and MCS were abnormal also in this cohort, compared with the Italian population at large. In particular, the ability to ambulate independently as well as toe and heel walk correlated well with QoL measures in our patients.     

Correspondence between neurophysiological and clinical measurements of chemotherapy‐induced peripheral neuropathy: secondary analysis of data from the CI‐PeriNomS study

Chemotherapy‐induced peripheral neuropathy (CIPN) lacks standardized clinical measurement. The objective of the current secondary analysis was to examine data from the CIPN Outcomes Standardization (CI‐PeriNomS) study for associations between clinical examinations and neurophysiological abnormalities. Logistic regression estimated the strength of associations of vibration, pin, and monofilament examinations with lower limb sensory and motor amplitudes. Examinations were classified as normal (0), moderately abnormal (1), or severely abnormal (2). Among 218 participants, those with class 1 upper extremity (UE) and classes 1 or 2 lower extremity (LE) monofilament abnormality were 2.79 (95% confidence interval [CI]: 1.28–6.07), 3.49 (95%CI: 1.61–7.55), and 4.42 (95%CI: 1.35–14.46) times more likely to have abnormal sural nerve amplitudes, respectively, compared to individuals with normal examinations. Likewise, those with class 2 UE and classes 1 or 2 LE vibration abnormality were 8.65 (95%CI: 1.81–41.42), 2.54 (95%CI: 1.19–5.41), and 7.47 (95%CI: 2.49–22.40) times more likely to have abnormal sural nerve amplitudes, respectively, compared to participants with normal examinations. Abnormalities in vibration and monofilament examinations are associated with abnormal sural nerve amplitudes and are useful in identifying CIPN.     

Clinical utility of electrodiagnostic consultation in suspected polyneuropathy

Although paresthesias of the distal lower limbs are characteristic features of polyneuropathy, they may also herald the presence of a focal neuropathy, polyradiculopathy, or myelopathy. Electromyography and nerve conduction studies (EMG/NCS) are widely used in the evaluation of such symptoms, but their utility has not been subjected to vigorous scrutiny. We investigated the clinical impact of the electrodiagnostic consultation in assessing suspected polyneuropathy. When compared with the clinical impression, the result of the electrodiagnostic consultation was confirmatory in only 39% of all patients, and changed the diagnosis or uncovered an additional diagnosis in 43%. An alternative diagnosis was likely when either weakness was present (75%) or the Achilles stretch reflex was preserved (48%). These data support the use of EMG/NCS in the diagnostic evaluation of patients presenting with distal paresthesias, especially in those with preserved Achilles reflexes or motor deficits.     

Review of neurophysiological findings in patients with schizophrenia

Schizophrenia has been conceptualized as a failure of cognitive integration, and abnormalities in neural circuitry have been proposed as a basis for this disorder. In this article, we focus on electroencephalography and magnetoencephalography findings in patients with schizophrenia. Auditory‐P50, ‐N100, and ‐P300 findings, visual‐P100, ‐N170, and ‐N400 findings, and neural oscillations in patients with schizophrenia are overviewed. Published results suggest that patients with schizophrenia have neurophysiological deficits from the very early phase of sensory processing (i.e. P50, P100, N100) to the relatively late phase (i.e. P300, N400) in both auditory and visual perception. Exploring the associations between neural substrates, including neurotransmitter systems, and neurophysiological findings, will lead to a more comprehensive understanding of the pathophysiology of schizophrenia.     

Chronic idiopathic axonal polyneuropathy revisited

Abstract. Objective: To investigate whether several years after the diagnosis chronic idiopathic axonal polyneuropathy (CIAP), the cause of the neuropathy is still idiopathic. Methods: All outpatients were included in this study in which, between 1993–2000, with the same guideline for chronic neuropathy, the diagnosis CIAP was made. We checked whether the patients had been evaluated according to this guideline. We evaluated the clinical course in all patients and repeated questions on the family history. We also re-examined these patients. After recording these data, we decided whether or not the neuropathy remained idiopathic. Results: A total of 478 outpatients had been evaluated, of these 53 were diagnosed as CIAP. Of these the diagnosis remained CIAP in 27 (51%) patients. In 19 (36%) of the patients a wrong diagnosis was made, explained by not following the diagnostic guideline, and by not recognising hereditary neuropathies. Conclusion: In half of the patients with the diagnosis CIAP, this diagnosis was changed after revision, including the family history of neuropathies. Therefore, in patients with the diagnosis CIAP, this diagnosis should be reconsidered. In addition the question should be whether the hereditary neuropathies have been excluded.     

Functioning of patients with chronic idiopathic axonal polyneuropathy (CIAP)

Abstract Although patients with Chronic Idiopathic Axonal Polyneuropathy (CIAP) report a slow deterioration of sensory and motor functions, the impact of this deterioration on daily functioning has not yet been investigated in detail. The first aim of this crosssectional study involving 56 patients with CIAP was, therefore, to assess patients' functioning with use of the International Classification of Functioning, Disability and Health (ICF). The second aim was to find determinants of walking ability, dexterity, and autonomy. Fatigue and limited walking ability were present in most patients and differed considerably. In regression models, age, muscle strength, and fatigue together explained 63% of the variance in walking ability, which by itself explained almost 50% of the variance in patients' autonomy indoors and outdoors (42% and 49%, respectively). Muscle strength and sensory function scores together explained 30% of the variance in dexterity scores, which in turn explained only 13% of the variance in autonomy indoors. The diminished autonomy of patients with CIAP might be improved by reducing fatigue, by means of training, and by improving walking ability.     

Severe axonal polyneuropathy with onset in the postpartum period

We report two patients who presented severe polyneuropathy in the postpartum period. Electrophysiological studies evidenced an axonal process which was associated with proximal demyelination in the second patient. In both cases, a peripheral nerve biopsy showed severe axonal Wallerian-like degeneration and no feature of demyelination. The first patient had a dramatic loss of myelinated fibres, and severe disability persisted for several months. These two patients are different from cases of acute or chronic inflammatory demyelinating polyradiculoneuropathy previously reported in relation with pregnancy.     

Cisplatin neuropathy: clinical course and neurophysiological findings

Summary Sixteen patients treated with cisplatin (CDDP) 40 mg/m² on days 1–5 every 4 weeks for three courses (cumulative dose 600 mg/m²) were clinically and neurophysiologically tested before, during and 1, 3, 6, 9 and 12 months after CDDP administration. The first symptoms of polyneuropathy occurred in 4 of 9 patients after the second course (cumulative dose 400 mg/m²). One month after treatment 1 of 9 patients was asymptomatic, 5 complained of symptoms and 3 showed clinical and neurophysiological signs of polyneuropathy. Three months after CDDP all patients were affected. Clinical and neurophysiological signs of severity progression were noted up to 6 months after treatment with CDDP.     

转甲蛋白相关家族性淀粉样周围神经病的临床、病理与遗传学研究

目的 探讨转甲蛋白相关家族性淀粉样周围神经病(TTR-FAP)患者的临床、电生理、组织病理和遗传学表现.方法 对北京协和医院2006-2014年确诊的13个家系(先证者)和散发TTR-FAP病例进行临床观察、分期、系统评估和随访.对其中12例进行了周围神经和(或)肌肉活组织检查(活检),主要采用腓浅神经与腓骨短肌联合活检.同时采用转甲蛋白免疫组织化学染色和转甲蛋白基因检测.结果 (1)临床表现:13例先证者和散发病例,男性11例,女性2例,发病年龄17 ～53岁,平均37.7岁.5例以周围神经病起病;4例以晕厥和(或)短暂脑缺血发作样症状起病;4例以腹泻起病.从发病到确诊的平均时间为2.96年.全部患者均有感觉和运动性周围神经病和自主神经功能障碍.临床分期1期4例,2期5例,3期4例.(2)神经肌肉活检病理:周围神经病理改变为慢性活动性轴索性损害,肌肉病理改变以神经源性损害为主,刚果红和转甲蛋白免疫组织化学染色阳性,提示转甲蛋白阳性物质淀粉样物质在神经与肌肉中沉积.(3)基因检测发现10种点突变,其中E54Q点突变未见报道.(4)诊疗与转归:对全部患者予维生素营养神经治疗,3例近期予二氟尼柳治疗,5例于发病后3～6年死亡.结论 TTR-FAP呈现基因型和临床表型的多样性,经典的V30M型在我国可能不是优势类型.本组病例以早发型为主,部分患者进展迅速,可能与特定的基因突变类型有关.神经肌肉联合活检加转甲蛋白免疫组织化学染色可提供TTR-FAP组织学确诊证据.     

慢性特发性轴索性多神经病的病理及免疫组化研究

目的 研究慢性特发性轴索性多神经病(chronic idiopathic axonal polyneuropathy,CIAP)病理改变特点,并探索腓肠神经炎细胞CD3、CD20、CD68抗体及其微小血管内皮细胞膜结合性血栓调节蛋白(thrombomodulin,TM)、内皮源性一氧化氮合酶(endothelial-nitricoxide synthase,e NOS)的表达规律。方法 10例经过临床、电生理、腓肠神经活检病理检查证实的CIAP患者,均进行腓肠神经活检标本的常规病理组织学染色以及以抗CD3、CD20、CD68、TM、e NOS、v WF(von Willebrand factor,v WF)抗体作为第一抗体的免疫组织化学染色。结果 10例患者腓肠神经病理检查显示有髓神经纤维轻-中度减少,伴随轴索变性和再生,部分可见轻微脱髓鞘改变,4例患者出现毛细血管基底膜肥厚。4例患者腓肠神经神经束衣间小血管周围有散在分布的CD68阳性单核细胞浸润。所有患者血管内皮细胞v WF、e NOS、TM均正常表达。结论 CIAP病理特点为轴索损害为主,发病可能和体液免疫异常有关,部分患者毛细血管基底膜肥厚提示血管内皮细胞可能受损,但内皮细胞功能相关蛋白表达初步提示正常。     

Trithiozine polyneuropathy: clinical, neurophysiological and histopathological study of three cases

3 peptic ulcer patients, treated for a few weeks with Trithiozine, developed polyneuropathy. The histopathological patterns in the 2 patients in whom sural nerve biopsy was done presented wallerian degeneration of the axons of the myelinated fibers, especially those of larger caliber. The evidence for a iatrogenic toxic etiology is discussed.

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Sommario Gli Autori descrivono tre casi di polineuropatia insorta in pazienti ulcerosi e trattati per alcune settimane con Tritiozina. I quadri istopatologici osservati in due pazienti in cui si è ottenuta biopsia del nervo surale, evidenziano una sofferenza assonale del tipo della degenerazione walleriana a carico delle fibre mieliniche, specie di maggior calibro. Vengono discussi gli elementi a favore di una origine tossico-iatrogena del quadro clinico osservato.

     

Acute idiopathic axonal neuropathy (AIAN): a clinical and electrophysiological observation

Twenty patients (M:F 15:5) with electrophysiological evidence of predominant axonal lesion and fulfilling clinical criteria for Guillain Barré Syndrome were observed during a period of 6 years (1985–1990). Their mean age was 27.5 years (range 5–55). Seven patients had antecedent febrile illness. Peak motor deficit was reached at a mean period of 6.5 days (range 2–21 days). All the patients had distal muscle weakness out of proportion to proximal muscle weakness. Facial paresis (13 patients), bulbar palsy (2), respiratory failure (1), sensory deficits (7) and dysautonomia (1) were other salient features. CSF analysis revealed albuminocytological dissociation in 12 patients. One patient died and in the remaining patients the recovery was delayed and incomplete. Presence of predominant distal muscle wasting and weakness, low amplitude CMAP or inexcitable nerves, absence of conduction block or significant temporal dispersion, normal or only slightly reduced conduction velocity and evidence of poor recovery suggest that the primary pathology in these patients may be axonal degeneration. These cases may represent a distinct entity and need to be differentiated from the more commonly observed acute idiopathic demyelinating neuropathy.     

Excessive fragmentary hypnic myoclonus: clinical and neurophysiological findings

BACKGROUND: Brief involuntary sleep-related twitches occurring asymmetrically throughout the body define physiologic hypnic fragmentary myoclonus. An abnormal intensification of this entity identifies excessive fragmentary hypnic myoclonus (EFHM), a 'proposed sleep disorder' in the International Sleep Disorders Classification. METHODS: We describe two patients with EFHM, one associated with a REM behaviour disorder. RESULTS: EFHM activity was restricted to sleep prevailing during NREM sleep stages and the second part of the night. EMG was normal and EEG-EMG back-averaging did not show any cortical potentials related to the twitches. CONCLUSIONS: EFHM represents a pathological phenomenon which may or may not be associated with other sleep disorders. A brainstem generator explains its distribution throughout the body and the sleep stages.     

Idiopathic spinal myoclonus: A clinical and neurophysiological assessment of a movement disorder of uncertain origin

Spinal Myoclonus (SM) is characterized by brief and sudden movements caused by the activation of muscles belonging to adjacent spinal myotomes. Recent reports have indicated that “typical” clinical and electrophysiological features of SM can be mimicked voluntarily. A useful tool that can distinguish between organic and psychogenic jerks is the detection of a Bereitschaftspotential (BP). In this study, we looked for evidence of a BP in a cohort of patients with idiopathic SM. A clinical and neurophysiological assessment of 20 patients affected by idiopathic SM was performed. A video EEG‐EMG multichannel recording was performed in each patient to detect BP. An expert neurophysiologist (PB) reviewed the BP recordings and divided them into those showing a definite, possible, and no BP. A clinical assessment of the videoed movements was performed by two neurologists expert in movement disorders (KB and MJE) who indicated if the movements were compatible with organic or psychogenic myoclonus. A definite or possible BP was recorded in 15 out of 20 patients. Clinical raters agreed in their clinical opinion on 15 patients (75%). All patients where both raters agreed the movements appeared to be organic had definite or possible BP. BP are commonly seen in patients with idiopathic SM. There is discordance between clinicians in their clinical rating of SM as organic or psychogenic, but even in those patients where movements appear clinically to be organic, a BP is commonly detected, indicating that the aetiology is psychogenic. This suggests that BP recordings are a useful adjunct to clinical assessment in the accurate diagnosis of patients with idiopathic SM. © 2009 Movement Disorder Society