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BACKGROUND: Biallelic SUFU variants have originally been linked to Joubert syndrome, comprising cerebellar abnormalities, dysmorphism, and polydactyly. In contrast, heterozygous truncating variants have recently been associated with developmental delay and ocular motor apraxia, but only a limited number of patients have been reported. Here, we aim to delineate further the mild end of the phenotypic spectrum related to SUFU haploinsufficiency. METHODS: Nine individuals (from three unrelated families) harboring truncating SUFU variants were investigated, including two previously reported individuals (from one family). We provide results from a comprehensive assessment comprising neuroimaging, neuropsychology, video-oculography, and genetic testing. RESULTS: We identified three inherited or de novo truncating variants in SUFU (NM_016169.4): c.895C>T p.(Arg299∗), c.71dup p.(Ala25Glyfs∗23), and c.71del p.(Pro24Argfs∗72). The phenotypic expression showed high variability both between and within families. Clinical features include motor developmental delay (seven of nine), axial hypotonia (five of nine), ocular motor apraxia (three of nine), and cerebellar signs (three of nine). Four of the six reported children had macrocephaly. Neuropsychological and developmental assessments revealed mildly delayed language development in the youngest children, whereas general cognition was normal in all variant carriers. Subtle but characteristic SUFU-related neuroimaging abnormalities (including superior cerebellar dysplasia, abnormalities of the superior cerebellar peduncles, rostrally displaced fastigium, and vermis hypoplasia) were observed in seven of nine individuals. CONCLUSIONS: Our data shed further light on the mild but recognizable features of SUFU haploinsufficiency and underline its marked phenotypic variability, even within families. Notably, neurodevelopmental and behavioral abnormalities are mild compared with Joubert syndrome and seem to be well compensated over time.
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BACKGROUND AND PURPOSE: Patent foramen ovale (PFO)is associated with cryptogenic stroke, especially in young adults. Transcranial Doppler (TCD) ultrasound is used as a screening tool before transesophageal echocardiography (TEE). However, the use of Valsalva maneuver (VM) to identify a right-to-left-shunt underlies interindividual variability. Here, we aimed to assess whether a pressure-controlled standardization of VM is useful to estimate PFO size. METHODS: We included patients aged 18-80 years with a PFO according to TEE. Subjects underwent TCD with microembolic signals (MES) counted under four pressure conditions (i.e., at rest, 15 mbar, 40 mbar, and maximum expiratory pressure). Findings were correlated with TEE-based PFO size. The predictive value of TCD at rest and VM-based TCD for PFO size estimation was assessed by stepwise multivariate linear regression models and multiple cross-tab-analyses. RESULTS: We screened 203 subjects after a cerebrovascular event, of which 78 (48 males [61.5%], median age 55 years [22-80]) with PFO were included. We found an association between MES count and expiratory pressure (p < .001). Predefined MES count categories at TCD pressure conditions correlated significantly with PFO size measured by TEE. We propose a PFO size estimation model based on TCD at rest and under VM, which classified PFO size correctly in 64.1% with the highest accuracy for small PFOs. CONCLUSION: Our data provide evidence that TCD with step-wise barometric standardization allows an estimation of PFO size with good accuracy. Though TCD will not replace TEE in future, this might be of clinical value in circumstances where TEE cannot be easily performed.
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Forame Oval Patente , AVC Isquêmico , Acidente Vascular Cerebral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ecocardiografia Transesofagiana/métodos , Forame Oval Patente/complicações , Forame Oval Patente/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Ultrassonografia Doppler Transcraniana/métodos , Manobra de Valsalva , Adulto JovemRESUMO
The diagnostic criteria published by the PNS (Paraneoplastic Neurological Syndromes) Euronetwork in 2004 provided a useful classification of PNS, including paraneoplastic neuropathies. Subacute sensory neuronopathy (SSN) was the most frequently observed peripheral PNS, whereas other forms of neuropathy, as sensory polyneuropathy, sensorimotor polyneuropathy, demyelinating neuropathies, autonomic neuropathies, and focal nerve or plexus lesions, were less frequent. At the time of publication, the main focus was on onconeural antibodies, but knowledge regarding the mechanisms has since expanded. The antibodies associated with PNS are commonly classified as onconeural (intracellular) and neuronal surface antibodies (NSAbs). Since 2004, the number of antibodies and the associated tumors has increased. Knowledge has grown on the mechanisms underlying the neuropathies observed in lymphoma, paraproteinemia, and multiple myeloma. Moreover, other unrevealed mechanisms underpin sensorimotor neuropathies and late-stage neuropathies, where patients in advanced stages of cancer-often associated with weight loss-experience some mild sensorimotor neuropathy, without concomitant use of neurotoxic drugs. The spectrum of paraneoplastic neuropathies has increased to encompass motor neuropathies, small fiber neuropathies, and autonomic and nerve hyperexcitability syndromes. In addition, also focal neuropathies, as cranial nerves, plexopathies, and mononeuropathies, are considered in some cases to be of paraneoplastic origin. A key differential diagnosis for paraneoplastic neuropathy, during the course of cancer disease (the rare occurrence of a PNS), is chemotherapy-induced peripheral neuropathy (CIPN). Today, novel complications that also involve the peripheral nervous system are emerging from novel anti-cancer therapies, as targeted and immune checkpoint inhibitor (ICH) treatment. Therapeutic options are categorized into causal and symptomatic. Causal treatments anecdotally mention tumor removal. Immunomodulation is sometimes performed for immune-mediated conditions but is still far from constituting evidence. Symptomatic treatment must always be considered, consisting of both drug therapy (e.g., pain) and attempts to treat disability and neuropathic pain.
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This study investigated treatment characteristics of Guillain-Barré syndrome (GBS) in a real-world setting between 2000 and 2019. We analyzed clinical improvement between nadir and last follow-up in patients with severe GBS (defined as having a GBS disability scale > 2 at nadir) and aimed to detect clinical factors associated with multiple treatments. We included 121 patients (74 male; median age 48 [IQR 35-60]) with sensorimotor (63%), pure motor (15%), pure sensory (10%) and localized GBS (6%) as well as Miller Fisher syndrome (6%). 44% of patients were severely affected. All but one patient received at least one immunomodulatory treatment with initially either intravenous immunoglobulins (88%), plasma exchange (10%) or corticosteroids (1%), and 25% of patients received more than one treatment. Severe GBS but not age, sex, GBS subtype or date of diagnosis was associated with higher odds to receive more than one treatment (OR 4.22; 95%CI 1.36-13.10; p = 0.01). Receiving multiple treatments had no adjusted effect (OR 1.30, 95%CI 0.31-5.40, p = 0.72) on clinical improvement between nadir and last follow-up in patients with severe GBS. This treatment practice did not change over the last 20 years.
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Corticosteroides/uso terapêutico , Síndrome de Guillain-Barré/terapia , Imunoglobulinas Intravenosas/uso terapêutico , Troca Plasmática/métodos , Adulto , Áustria , Feminino , Síndrome de Guillain-Barré/imunologia , Humanos , Imunoglobulinas Intravenosas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Síndrome de Miller Fisher/terapia , Recuperação de Função Fisiológica , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Albuminocytologic dissociation in cerebrospinal fluid (CSF) is a diagnostic hallmark of Guillain-Barré syndrome (GBS). Compared to CSF total protein (TP), the CSF/serum albumin quotient (Qalb) has the advantage of method-independent reference ranges. Whether the diagnostic yield differs between Qalb and CSF-TP is currently unknown. METHODS: We retrospectively analyzed the diagnostic yield (i.e., a value above the URL indicating blood-nerve barrier dysfunction) of Qalb and CSF-TP levels in patients with GBS. We evaluated two different equations (Reiber's and Hegen's) for age-adjusted URLs of Qalb and compared results to CSF-TP using the standard URL of 0.45 g/L as well as age-adjusted URLs (by decade of age). Additionally, multivariable logistic regression analysis was used to assess the effect of clinical factors on the diagnostic yield. RESULTS: We analyzed 110 patients [62% males; median age 48 (IQR 35-58)] with sensorimotor (68), motor (16), sensory (12) and localized (8) GBS as well as Miller Fisher syndrome (6). Qalb and CSF-TP were highly correlated (r = 0.95, p < 0.001). The diagnostic yield of Qalb was 65% with Reiber's and 47% with Hegen's age-adjusted URLs compared to 66% with the fixed CSF-TP URL of 0.45 g/L and 49% with age-adjusted CSF-TP URLs. A longer duration from clinical onset to lumbar puncture was associated with a higher diagnostic yield. CONCLUSION: Qalb strongly correlates with CSF-TP in patients with GBS with a similar diagnostic yield for the detection of a blood-nerve barrier dysfunction. However, the diagnostic yield of both values is lower when using more recent age-adjusted URLs and at earlier timepoints.
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Síndrome de Guillain-Barré , Albumina Sérica Humana , Adulto , Líquido Cefalorraquidiano , Proteínas do Líquido Cefalorraquidiano , Feminino , Síndrome de Guillain-Barré/líquido cefalorraquidiano , Síndrome de Guillain-Barré/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome de Miller Fisher , Estudos RetrospectivosRESUMO
OBJECTIVE: Nerve conduction studies (NCS) are essential to differentiate between demyelinating and axonal subtypes in Guillain-Barré syndrome (GBS). However, it is debated to which extent the delay of NCS after symptom onset and repeated measurements during the disease course influence the diagnostic accuracy. METHODS: We evaluated NCS in 93 patients with a classical GBS applying two widely used criteria (Hadden's and Rajabally's). The initial measurements after symptom onset were compared to follow-up studies where available (n = 43). We analyzed the influence of NCS timing after symptom onset and clinical severity on fulfilling the electrophysiological criteria for axonal or demyelinating subtypes and evaluated the impact of repeated measurements. We further evaluated the presence of reversible conduction failure. RESULTS: A higher GBS disability scale at nadir correlated with a successful subclassification whereas the delay of the first NCS after symptom onset did not influence the diagnostic yield (75% for Hadden's and 68% for Rajabally's criteria for the first assessment). A second measurement allowed the additional successful classification in 19% and 14% of patients, respectively. On the other hand, a repeated measurement in patients with an initial successful classification resulted in a different subtype in 5% and 7%, respectively. Reversible conduction failure was found in 7% of patients. CONCLUSION: Clinical severity but not timing of NCS influenced the fulfilment of electrophysiological criteria for either the axonal or demyelinating subtype. Repeated electrophysiological measurements led to a further specification or a change in subtype classification in a relevant proportion of patients.
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Síndrome de Guillain-Barré , Condução Nervosa , Progressão da Doença , Seguimentos , Síndrome de Guillain-Barré/diagnóstico , Humanos , Exame NeurológicoRESUMO
Glioblastoma might have widespread effects on the neural organization and cognitive function, and even focal lesions may be associated with distributed functional alterations. However, functional changes do not necessarily follow obvious anatomical patterns and the current understanding of this interrelation is limited. In this study, we used resting-state functional magnetic resonance imaging to evaluate changes in global functional connectivity patterns in 15 patients with glioblastoma. For six patients we followed longitudinal trajectories of their functional connectome and structural tumour evolution using bi-monthly follow-up scans throughout treatment and disease progression. In all patients, unilateral tumour lesions were associated with inter-hemispherically symmetric network alterations, and functional proximity of tumour location was stronger linked to distributed network deterioration than anatomical distance. In the longitudinal subcohort of six patients, we observed patterns of network alterations with initial transient deterioration followed by recovery at first follow-up, and local network deterioration to precede structural tumour recurrence by two months. In summary, the impact of focal glioblastoma lesions on the functional connectome is global and linked to functional proximity rather than anatomical distance to tumour regions. Our findings further suggest a relevance for functional network trajectories as a possible means supporting early detection of tumour recurrence.
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Neoplasias Encefálicas/patologia , Conectoma , Glioblastoma/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/fisiopatologia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/fisiopatologia , Cerebelo/patologia , Cerebelo/fisiopatologia , Neuroimagem Funcional , Glioblastoma/diagnóstico por imagem , Glioblastoma/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Vias Neurais/diagnóstico por imagem , Vias Neurais/patologia , Vias Neurais/fisiopatologiaRESUMO
Myasthenic syndromes are typically characterized by muscle weakness and increased fatigability due to an impaired transmission at the neuromuscular junction (NMJ). Most cases are caused by acquired autoimmune conditions such as myasthenia gravis (MG), typically with antibodies against the acetylcholine receptor (AChR). Different drugs are among the major factors that may complicate pre-existing autoimmune myasthenic conditions by further impairing transmission at the NMJ. Some clinical observations are substantiated by experimental data, indicating that presynaptic, postsynaptic or more complex pathomechanisms at the NMJ may be involved, depending on the individual compound. Most robust data exist for the risks associated with some antibiotics (e.g., aminoglycosides, ketolides, fluoroquinolones) and cardiovascular medications (e.g., class Ia antiarrhythmics, beta blockers). Apart from primarily autoimmune-mediated disorders of the NMJ, de novo myasthenic manifestations may also be triggered by medical treatments that induce an autoimmune reaction. Most notably, there is growing evidence that the immune checkpoint inhibitors (ICI), a modern class of drugs to treat various malignancies, represent a relevant risk factor to develop severe and progressive medication-induced myasthenia via an immune-mediated mechanism. From a clinical perspective, it is of utmost importance for the treating physicians to be aware of such adverse treatment effects and their consequences. In this article, we aim to summarize existing evidence regarding the key molecular and immunological mechanisms as well as the clinical implications of medication-aggravated and medication-induced myasthenic syndromes.
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BACKGROUND: Brain metastases (BM) are a frequent complication of advanced cancer and are characterized by a variety of neurological symptoms. Although the presence of neurological symptoms is included in the response assessment in patients with primary brain tumors, to the authors' knowledge little is known regarding the prognostic impact of neurological symptoms in patients with BM. METHODS: Patients with newly diagnosed BM from non-small cell lung cancer were identified from the Vienna Brain Metastasis Registry and were evaluated according to the incidence, distribution, and prognostic impact of neurological symptoms at the time of diagnosis of BM. RESULTS: A total of 1608 patients (57.3% male and 42.7% female; median age, 62 years) were available for further analyses. Neurological symptoms including focal deficits (985 patients; 61.3%), signs of increased intracranial pressure (483 patients; 30.0%), epileptic seizures (224 patients; 13.9%), and neuropsychological symptoms (233 patients; 14.5%) were documented in 1186 of the 1608 patients (73.8%). Patients with asymptomatic BM presented with a longer median overall survival after the diagnosis of BM compared with patients with symptomatic BM (11 months vs 7 months; P < .001). In multivariate analysis with a diagnosis-specific graded prognostic assessment (hazard ratio, 1.41; 95% CI, 1.33-1.50 [P < .001]), the presence of neurological symptoms (hazard ratio, 1.39; 95% CI, 1.23-1.57 [P < .001]) was found to be independently associated with survival prognosis from the time of diagnosis of BM. CONCLUSIONS: Neurological symptoms at the time of BM diagnosis demonstrated a strong and independent association with survival prognosis. The results of the current study have highlighted the need for the integration of the presence of neurological symptoms into the prognostic assessment of patients with BM from non-small cell lung cancer. LAY SUMMARY: Neurological symptom evaluation is included regularly in the assessment of patients with primary brain tumors. However, to the authors' knowledge, little is known regarding the prognostic impact in patients with newly diagnosed brain metastases (BM). The current study has provided a detailed clinical characterization of the incidence, distribution, and prognostic impact of neurological symptoms in a large, real-life cohort of patients with BM from non-small cell lung cancer. In this cohort, neurological symptoms at the time of diagnosis of BM demonstrated a strong, independent prognostic impact on the survival prognosis. The results of the current study have highlighted the need for the integration of neurological symptom burden into the prognostic assessment of patients with BM from non-small cell lung cancer.
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Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/complicações , Neoplasias Pulmonares/complicações , Doenças do Sistema Nervoso/etiologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/patologia , PrognósticoRESUMO
PURPOSE: To determine the extent of retinal and corneal neurodegeneration and investigate the association with intraepidermal neuronal loss and diabetic peripheral neuropathy (DPN) in type 2 diabetes. DESIGN: Prospective, cross-sectional study. METHODS: Single-center study of 94 patients with type 2 diabetes patients (157 eyes), divided into groups: the groups without diabetic retinopathy (DR) (n = 68); the nonproliferative DR (NPDR) group (n = 48); and the proliferative DR (PDR) group (n = 41). Patients were imaged with optical coherence tomography and confocal microscopy for macular and peripapillary neuroretinal layer thicknesses and corneal nerve length/density, respectively. Distal leg skin punch biopsies and 2 neurological scores were used to depict intraepidermal nerve fiber density (IENFD) and clinical DPN. RESULTS: Among neuroretinal layers, solely the peripapillary retinal nerve fiber layer was decreased in PDR (96 µm; 95% confidence interval [CI], 92-100 µm) versus no DR (103 µm; 95% CI, 100-106 µm) eyes and only after exclusion of outliers (P = .01). Corneal nerve fiber length and density were statistically significantly reduced in the NPDR group (23.0 mm/mm2; 95% CI, 20.0-26.00 mm/mm2 and 14.3 mm; 95% CI, 14.5-16.63 mm, respectively) and the PDR group (18.6 mm/mm2; 95% CI, 14.9-22.30 mm/mm2 and 11.7 mm; 95% CI, 10.2-13-3 mm, respectively) versus the no DR group (25.5 mm/mm2; 95% CI, 23.3-27.70 mm/mm2 and 15.6 mm; 95% CI, 14.5-16.6 mm, respectively), and in the PDR versus the NPDR group. IENFD was statistically significantly reduced in the NPDR (2.0/mm; 95% CI, 1.4-2.7/mm) and PDR stage (1.4/mm; 95% CI, 0.9-2.1/mm) versus in eyes without DR (3.6/mm; 95% CI, 2.9-4.6/mm). A low correlation between intraepidermal and corneal fiber loss was found with both neurological scores (P < .05). CONCLUSIONS: Retinal neurodegenerative changes may develop independently of the microvascular alterations defining DR. Corneal and intraepidermal neuronal loss is more pronounced in advanced stages of DR, indicating a positive severity correlation between DR and DPN.
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Córnea/inervação , Distrofias Hereditárias da Córnea/diagnóstico , Diabetes Mellitus Tipo 2/diagnóstico , Neuropatias Diabéticas/diagnóstico , Retinopatia Diabética/diagnóstico , Degeneração Retiniana/diagnóstico , Nervo Trigêmeo/patologia , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Microscopia Confocal , Pessoa de Meia-Idade , Fibras Nervosas/patologia , Estudos Prospectivos , Células Ganglionares da Retina/patologia , Tomografia de Coerência ÓpticaRESUMO
BACKGROUND: So far, the development and course of therapy-induced deficiencies in hypothalamic-pituitary hormones in adult patients with malignant gliomas has not received much attention. However, such deficiencies may impact patient's quality of life substantially. METHODS: In this monocentric longitudinal trial, we examined hormonal levels of TSH, T3, T4, fT3, fT4, FSH, LH, testosterone, estradiol and prolactin in patients with malignant high grade gliomas before the start of radiochemotherapy (RCT), at the end of RCT and then every three months for newly diagnosed patients and every six months in patients diagnosed more than two years before study inclusion. Growth hormone was not measured in this trial. RESULTS: 436 patients (198 female, 238 male) with high-grade gliomas, aged 19-83â¯years (median 50â¯years), were included in this study. Low levels of thyroid hormones were observed in around 10% of patients within the first six months of follow up and increasingly after 36â¯months. Half of premenopausal women at study entry developed premature menopause, 35% showed hyperprolactinemia. Low testosterone levels were measured in 37% of men aged less than 50â¯years and in 35/63 (55%) of men aged 50â¯years or older. DISCUSSION: The results of this study show that a significant percentage of patients with malignant gliomas develop hormonal deficiencies mandating regular clinical follow up, state of the art counseling and if clinically necessary substitution therapy.
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Neoplasias Encefálicas/terapia , Quimiorradioterapia/efeitos adversos , Glioma/terapia , Hipogonadismo/etiologia , Hipotireoidismo/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/sangue , Feminino , Glioma/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Prolactina/sangue , Estudos Prospectivos , Testosterona/sangue , Hormônios Tireóideos/sangueRESUMO
The treatment of malignant tumors has considerably improved in recent years, and also the number of "long term cancer survivors" is increasing.The spectrum of anti-tumoral agents is increasing at a fast pace and in addition to conventional therapies such as surgery, radiotherapy, and chemotherapy, new drugs with entirely new mechanisms are appearing. Side effects of old and new drugs can affect the central and peripheral nervous system, the neuromuscular junction, and muscle. These side effects often have to be distinguished from other causes and need neurological expertise. Although the majority of patients still receive conventional therapies, several new strategies such as immune therapies are being implemented. These drugs have also drug specific side effects, which do not always follow the classical principles of "toxicity."This review focuses on the well-known and described side effects of conventional cancer therapies and adds new observations on new drugs.
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Antineoplásicos/uso terapêutico , Imunoterapia , Neoplasias , Humanos , Neoplasias/terapiaRESUMO
OBJECTIVE: To determine the proportion of true and false positives from paraneoplastic panels and effects on downstream testing/treatment. METHODS: Using a retrospective cohort study design, we identified 500 consecutive patients with Mayo paraneoplastic autoantibody testing and performed chart abstraction. Paraneoplastic presentation types were categorized into probable, possible, and other by consensus. True positives were defined as a positive antibody titer with no other explanation found in addition to one of the following: syndrome known to be associated with the antibody, clinical improvement with treatment, and new malignancy. Comparisons of diagnostic testing and treatments between false and true positives were performed. Multivariable logistic regression was used to evaluate associations between patient-level factors and true positives. RESULTS: The mean (SD) age of the population was 55.4 (17.1) years, and 55.4% were female, with 1.3 (1.2) years of follow-up. Of the 500 tests, 87 (17.4%, 95% confidence interval [CI] 14.1%-20.7%) were positive and 62 (71.3%, 95% CI 61.8%-80.8%) of these were false positives. Of those with a possible/other presentation (n = 369), 2 (0.5%, 95% CI 0.0%-1.0%) were true positives. CT of the chest (30.7% vs 11.8%, p ≤ 0.01) was performed more often in false positives than true negatives. Probable presentation type (odds ratio [OR] 57.9, 95% CI 12.5-268.0) and outpatient setting (OR 8.7, 95% CI 2.4-31.8) were associated with true-positive results. CONCLUSION: Paraneoplastic tests result in a large proportion of false positives, particularly in those with clinical presentations that are not well established as paraneoplastic diseases. Future work should construct panels targeted to specific clinical presentations and ensure that tests are ordered in the appropriate clinical context.
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Síndromes Paraneoplásicas/diagnóstico , Adulto , Idoso , Autoanticorpos/sangue , Reações Falso-Positivas , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
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.
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Antineoplásicos/toxicidade , Neoplasias/tratamento farmacológico , Síndromes Neurotóxicas/etiologia , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Humanos , Síndromes Neurotóxicas/terapia , Doenças do Sistema Nervoso Periférico/terapiaRESUMO
PURPOSE OF REVIEW: Diabetic peripheral neuropathy (DPN) is a disabling, highly prevalent complication of both type 1 and type 2 diabetes mellitus (T1DM and T2DM). Large clinical studies support the concept that, in addition to hyperglycemia, components of the metabolic syndrome (MetS) may underlie the pathogenesis of DPN, especially in T2DM. This review will present the evidence supporting the MetS and its individual components as potential causal factors for the development of neuropathy. RECENT FINDINGS: In addition to poor glycemic control and duration of diabetes, components of MetS such as dyslipidemia, obesity, and hypertension may have an important impact on the prevalence of DPN. Obesity and prediabetes have the most data to support their role in neuropathy, whereas hypertension and dyslipidemia have more mixed results. Nonmetabolic factors, such as genetic susceptibility, age, height, sex, smoking, and alcohol, have also been highlighted as potential risk factors in peripheral neuropathy, although the exact contribution of these factors to DPN remains unknown. SUMMARY: DPN is a chronic and disabling disease, and the accurate identification and modification of DPN risk factors is important for clinical management. Recent data support a role for components of the MetS and other risk factors in the development of DPN, offering novel targets beyond hyperglycemia for therapeutic development.