Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 6.267
Filter
2.
Food Nutr Bull ; 45(1_suppl): S53-S57, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38987880

ABSTRACT

Vitamin B12 deficiency can present with a variety of neurological and cognitive symptoms. Especially in elderly patients, vitamin B12 deficiency can be easily overlooked because symptoms may be attributed to comorbid conditions or solely to the aging process. In this case study, we present two patients, a 71-year-old man and a 74-year-old female, with vitamin B12 deficiency. The male patient had a history of (partial) resection of the ileum/jejunum/colon because of intestinal ischemia. The female patient had a history of hypothyroidism, type 2 diabetes with complications (including peripheral neuropathy), mitochondrial myopathy, and chronic lymphocytic leukemia. Both patients presented with severe fatigue, cognitive impairment, and impaired walking. Next to this, the male patient suffered from depressive symptoms and mild disorientation, and the female patient experienced neuropathic pain. She also mentioned a positive family history for B12 deficiency. The first patient had normal to high B12 levels because he was already on B12 injections (once every three weeks) because of an earlier diagnosed B12 deficiency. The female patient had B12 levels within normal range (holotranscobalamin 54 pmol/L) and her diagnosis was confirmed by elevated homocysteine and methylmalonic acid levels. Treatment with frequent hydroxocobalamin injections and other supplements significantly improved their cognitive, emotional, and motor functions. These cases underscore the need for a high level of clinical suspicion in elderly patients, also in cases of normal B12 levels but with clinical signs of deficiency and a positive risk factor, such as stomach or small bowel surgery or positive family history.


Plain language titleA case study of two elderly patients with vitamin B12 deficiency and neurological and cognitive complaintsPlain language summaryVitamin B12 deficiency in elderly patients can be easily overlooked as symptoms can also be caused by other age-related diseases or the aging process. In our article we present two elderly patients, a 71-year-old male and a 74-year-old female, with neurological complaints, such as severe fatigue, cognitive decline, and walking impairment. The male patient had a history of small bowel surgery, and the female patient mentioned that she had several siblings with B12 deficiency. Additionally, the male patient suffered from depressive symptoms and mild disorientation, and the female had severe pain in her legs. The male patient already received B12 injections because of an earlier B12 diagnosis, but with a relatively low frequency. The B12 levels of the female patients were within the normal range. However, her diagnoses could be confirmed with additional laboratory measurements, such as homocysteine and methylmalonic acid. Treatment with frequent B12 injections and other supplements significantly improved their cognitive, emotional, and motor functions. Our study shows that clinicians should carefully consider the possibility of B12 deficiency in elderly patients with cognitive and neurological complaints, also in patients with B12 levels within the normal range, but with risk factors such as family members with B12 deficiency or conditions that may impair the vitamin B12 uptake, such as previous stomach or small bowel surgery.


Subject(s)
Vitamin B 12 Deficiency , Vitamin B 12 , Humans , Vitamin B 12 Deficiency/complications , Aged , Female , Male , Vitamin B 12/administration & dosage , Vitamin B 12/blood , Cognitive Dysfunction/etiology , Peripheral Nervous System Diseases/etiology , Methylmalonic Acid/blood , Homocysteine/blood
3.
J Peripher Nerv Syst ; 29(2): 161-172, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38873841

ABSTRACT

Monoclonal gammopathy-related peripheral neuropathies encompass a spectrum of clinical presentations in which the monoclonal protein directly damages the tissues, including the peripheral nervous system. Given the prevalence of both peripheral neuropathy and monoclonal gammopathy in the general population, these conditions may overlap in clinical practice, posing a challenge for clinicians in determining causality. Therefore, a comprehensive understanding of primary clinical syndromes and their neurophysiological patterns is of great importance for accurate differential diagnoses and effective treatment strategies. In this article, we examine the main forms of monoclonal gammopathies that affect the peripheral nerve. We explore the clinical and electrophysiological aspects and their correlation with each syndrome's corresponding monoclonal protein type. This knowledge is essential for healthcare professionals to diagnose better and manage patients presenting with monoclonal gammopathy-related peripheral nervous system involvement.


Subject(s)
Paraproteinemias , Peripheral Nervous System Diseases , Humans , Paraproteinemias/complications , Paraproteinemias/diagnosis , Peripheral Nervous System Diseases/diagnosis , Peripheral Nervous System Diseases/etiology , Peripheral Nervous System Diseases/physiopathology
5.
Rinsho Shinkeigaku ; 64(6): 403-407, 2024 Jun 27.
Article in Japanese | MEDLINE | ID: mdl-38797687

ABSTRACT

A 44-year-old man was admitted due to a fever. He developed unconsciousness and respiratory failure, necessitating mechanical ventilation. After the administration of methylprednisolone and intravenous immunoglobulin for suspected autoimmune encephalitis, his consciousness and respiratory state improved. However, he exhibited pronounced tetraparalysis and impaired sensation below the neck. A spinal MRI revealed swelling of the entire spinal cord, indicating myelitis. Deep tendon reflexes were diminished in all extremities, and a nerve conduction study confirmed motor-dominant axonal polyneuropathy. Subsequently, he developed a fever and headache. Brain MRI demonstrated FLAIR hyperintensities in the basal ganglia and brain stem. CSF analysis for anti-glial fibrillary acidic protein (GFAP) antibody turned out positive, leading to the diagnosis of GFAP astrocytopathy. Although the steroid re-administration improved muscle strength in his upper limbs and reduced the range of diminished sensation, severe hemiparalysis remained. Severe GFAP astrocytopathy can be involved with polyneuropathy. Early detection and therapeutic intervention for this condition may lead to a better prognosis.


Subject(s)
Glial Fibrillary Acidic Protein , Humans , Male , Adult , Peripheral Nervous System Diseases/etiology , Astrocytes/pathology , Autoantibodies/cerebrospinal fluid , Methylprednisolone/administration & dosage , Magnetic Resonance Imaging , Biomarkers/cerebrospinal fluid , Polyneuropathies/etiology , Myelitis/etiology , Myelitis/diagnosis
6.
Jt Dis Relat Surg ; 35(2): 455-461, 2024 Mar 21.
Article in English | MEDLINE | ID: mdl-38727129

ABSTRACT

Case reports of plexopathy after prostate cancer are usually neoplastic. Radiation-induced lumbosacral plexopathy and insufficiency fractures have clinical significance due to the need to differentiate them from tumoral invasions, metastases, and spinal pathologies. Certain nuances, including clinical presentation and screening methods, help distinguish radiation-induced plexopathy from tumoral plexopathy. This case report highlights the coexistence of these two rare clinical conditions. Herein, we present a 78-year-old male with a history of radiotherapy for prostate cancer who developed right foot drop, severe lower back and right groin pain, difficulty in standing up and walking, and tingling in both legs over the past month during remission. The diagnosis of lumbosacral plexopathy and pelvic insufficiency fracture was made based on magnetic resonance imaging, positron emission tomography, and electroneuromyography. The patient received conservative symptomatic treatment and was discharged with the use of a cane for mobility. Radiation-induced lumbosacral plexopathy following prostate cancer should be kept in mind in patients with neurological disorders of the lower limbs. Pelvic insufficiency fracture should also be considered if the pain does not correspond to the clinical findings of plexopathy. These two pathologies, which can be challenging to diagnose, may require surgical or complex management approaches. However, in this patient, conservative therapies led to an improvement in quality of life and a reduction in the burden of illness.


Subject(s)
Fractures, Stress , Lumbosacral Plexus , Prostatic Neoplasms , Radiation Injuries , Humans , Male , Prostatic Neoplasms/radiotherapy , Aged , Lumbosacral Plexus/injuries , Lumbosacral Plexus/radiation effects , Lumbosacral Plexus/pathology , Fractures, Stress/etiology , Fractures, Stress/diagnostic imaging , Radiation Injuries/etiology , Radiation Injuries/diagnostic imaging , Pelvic Bones/injuries , Pelvic Bones/pathology , Pelvic Bones/diagnostic imaging , Pelvic Bones/radiation effects , Peripheral Nervous System Diseases/etiology , Magnetic Resonance Imaging , Radiotherapy/adverse effects
7.
Front Endocrinol (Lausanne) ; 15: 1338167, 2024.
Article in English | MEDLINE | ID: mdl-38742191

ABSTRACT

Objective: Diabetic peripheral neuropathy frequently occurs and presents severely in individuals suffering from type 2 diabetes mellitus, representing a significant complication. The objective of this research was to develop a risk nomogram for DPN, ensuring its internal validity and evaluating its capacity to predict the condition. Methods: In this retrospective analysis, Suqian First Hospital's cohort from January 2021 to June 2022 encompassed 397 individuals diagnosed with T2DM. A random number table method was utilized to allocate these patients into two groups for training and validation, following a 7:3 ratio. By applying univariate and multivariable logistic regression, predictive factors were refined to construct the nomogram. The model's prediction accuracy was assessed through metrics like the ROC area, HL test, and an analysis of the calibration curve. DCA further appraised the clinical applicability of the model. Emphasis was also placed on internal validation to confirm the model's dependability and consistency. Results: Out of 36 evaluated clinicopathological characteristics, a set of four, duration, TBIL, TG, and DPVD, were identified as key variables for constructing the predictive nomogram. The model exhibited robust discriminatory power, evidenced by an AUC of 0.771 (95% CI: 0.714-0.828) in the training cohort and an AUC of 0.754 (95% CI: 0.663-0.845) in the validation group. The congruence of the model's predictions with actual findings was corroborated by the calibration curve. Furthermore, DCA affirmed the clinical value of the model in predicting DPN. Conclusion: This research introduces an innovative risk nomogram designed for the prediction of diabetic peripheral neuropathy in individuals suffering from type 2 diabetes mellitus. It offers a valuable resource for healthcare professionals to pinpoint those at elevated risk of developing this complication. As a functional instrument, it stands as a viable option for the prognostication of DPN in clinical settings.


Subject(s)
Diabetes Mellitus, Type 2 , Diabetic Neuropathies , Nomograms , Humans , Diabetes Mellitus, Type 2/complications , Diabetic Neuropathies/diagnosis , Diabetic Neuropathies/epidemiology , Diabetic Neuropathies/etiology , Female , Male , Middle Aged , Retrospective Studies , Aged , Risk Factors , Risk Assessment/methods , Prognosis , Peripheral Nervous System Diseases/diagnosis , Peripheral Nervous System Diseases/etiology , Peripheral Nervous System Diseases/epidemiology , Adult
8.
Brain Nerve ; 76(5): 555-561, 2024 May.
Article in Japanese | MEDLINE | ID: mdl-38741496

ABSTRACT

Paraneoplastic disorders of the peripheral nervous system are immune-mediated neurological syndromes associated with tumors. Several clinical phenotypes have been associated with these disorders. Sensory neuronopathy is the most well-known clinical phenotype, and is caused by neuronal cell injury to the dorsal root ganglia. Symptoms of the peripheral nervous system usually lead to the discovery of tumors. Antineuronal antibodies are occasionally identified in the serum and/or cerebrospinal fluid of these patients. The prevalence of small-cell lung cancer is notable in these patients. Early tumor resection, coupled with the initiation of immunotherapy, may prove effective in improving and stabilizing clinical symptoms.


Subject(s)
Paraneoplastic Syndromes, Nervous System , Humans , Paraneoplastic Syndromes, Nervous System/therapy , Paraneoplastic Syndromes, Nervous System/diagnosis , Paraneoplastic Syndromes, Nervous System/immunology , Peripheral Nervous System Diseases/immunology , Peripheral Nervous System Diseases/therapy , Peripheral Nervous System Diseases/etiology , Immunotherapy , Autoantibodies/immunology
9.
Brain Nerve ; 76(5): 540-546, 2024 May.
Article in Japanese | MEDLINE | ID: mdl-38741494

ABSTRACT

Anti-myelin-associated glycoprotein (MAG) neuropathy, which occurs secondary to immunoglobulin (Ig)M paraproteinemia such as monoclonal gammopathy of undetermined significance, is characterized by slow progression, sensory or sensorimotor disturbances, and ataxia. The estimated prevalence of this neuropathy in Japan is 0.28 per 100,000 population with male preponderance. This neuropathy is diagnosed based on the detection of M protein and anti-MAG antibodies in patients' serum. Nerve conduction studies show prolonged distal latency, and histopathological evaluation of sural nerve biopsies shows widely spaced myelin on electron microscopy. Usually, immunotherapy, including administration of intravenous Ig and corticosteroids, is ineffective, and rituximab is beneficial in approximately 50% of patients. Novel therapies, such as administration of Bruton's tyrosine kinase inhibitors are expected to benefit patients with the MYD88L265P mutation.


Subject(s)
Myelin-Associated Glycoprotein , Humans , Myelin-Associated Glycoprotein/immunology , Peripheral Nervous System Diseases/diagnosis , Peripheral Nervous System Diseases/etiology , Peripheral Nervous System Diseases/immunology , Peripheral Nervous System Diseases/therapy
10.
Brain Nerve ; 76(5): 569-574, 2024 May.
Article in Japanese | MEDLINE | ID: mdl-38741498

ABSTRACT

Eosinophilic granulomatosis with polyangiitis (EGPA) is an antineutrophil cytoplasmic autoantibody-associated vasculitis secondary to inflammation of the small vessels. EGPA-induced neuropathy develops in approximately 90% of patients with peripheral blood eosinophilia and may lead to serious complications of the peripheral nervous system, necessitating emergency therapeutic intervention.


Subject(s)
Granulomatosis with Polyangiitis , Peripheral Nervous System Diseases , Humans , Peripheral Nervous System Diseases/etiology , Peripheral Nervous System Diseases/diagnosis , Granulomatosis with Polyangiitis/complications , Granulomatosis with Polyangiitis/diagnosis , Churg-Strauss Syndrome/complications , Churg-Strauss Syndrome/diagnosis , Antibodies, Antineutrophil Cytoplasmic/immunology
11.
Brain Nerve ; 76(5): 575-582, 2024 May.
Article in Japanese | MEDLINE | ID: mdl-38741499

ABSTRACT

Vasculitic neuropathy is commonly associated with systemic vasculitis, leading to ischemic damage to the peripheral nerves and axonal degeneration. The typical clinical manifestation of vasculitic neuropathy is a sensory-dominant multiple mononeuropathy often accompanied by pain. Although vasculitic neuropathy is caused by various systemic diseases, ANCA-associated vasculitis, secondary systemic vasculitis linked to various collagen diseases, and non-systemic vasculitic neuropathy hold particular significance. A comprehensive understanding of vasculitic neuropathy is crucial for its early diagnosis, contributing to an improved prognosis for this condition.


Subject(s)
Granulomatosis with Polyangiitis , Peripheral Nervous System Diseases , Humans , Peripheral Nervous System Diseases/etiology , Peripheral Nervous System Diseases/diagnosis , Granulomatosis with Polyangiitis/complications , Granulomatosis with Polyangiitis/diagnosis , Prognosis
12.
Brain Nerve ; 76(5): 605-611, 2024 May.
Article in Japanese | MEDLINE | ID: mdl-38741503

ABSTRACT

Neurological immune-related adverse events (irAEs) associated with cancer treatment with immune checkpoint inhibitors (ICI) present diverse clinical characteristics. Neurological irAEs affect the peripheral nervous system and muscles more than they affect the central nervous system. Among the various subsets of peripheral neuropathies, polyradiculoneuropathy, which includes Guillain-Barre syndrome and chronic inflammatory demyelinating polyneuropathy, stands out as the most severe form, leading to significant muscle weakness. ICIs can induce dysautonomia, including autoimmune autonomic ganglionopathy. Autonomic neuropathy represents a neurological irAE. Neurological irAEs of neuromuscular junctions include myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS). Diagnosing MG or myositis independently can be challenging when they occur as irAEs. Myocarditis is sometimes observed as an irAE in patients with MG and can cause both severe heart failure and lethal arrhythmias, resulting in fatal outcomes. Anti-Kv1.4 antibodies are biomarkers of the severe form of MG and myocarditis. The administration of ICI in patients with small cell lung cancer increases the risk of LEMS. The distinction between LEMS is an irAE or a manifestation of paraneoplastic neurological syndrome is unclear as both conditions share common immunological mechanisms.


Subject(s)
Muscular Diseases , Peripheral Nervous System Diseases , Humans , Peripheral Nervous System Diseases/immunology , Peripheral Nervous System Diseases/diagnosis , Peripheral Nervous System Diseases/etiology , Peripheral Nervous System Diseases/chemically induced , Muscular Diseases/immunology , Muscular Diseases/diagnosis , Muscular Diseases/chemically induced , Immune Checkpoint Inhibitors/adverse effects , Neoplasms/immunology , Neoplasms/drug therapy , Neoplasms/complications
13.
Brain Nerve ; 76(5): 588-597, 2024 May.
Article in Japanese | MEDLINE | ID: mdl-38741501

ABSTRACT

Sjögren's syndrome is often accompanied by various neurological complications, among which peripheral neuropathy is the most common. A variety of clinical phenotypes of peripheral neuropathy, including axonal polyneuropathy and sensory ataxic neuropathy are reported in the literature. We present an overview of the pathophysiology and differential diagnosis of each phenotype. Immunotherapy using corticosteroids and high-dose intravenous immunoglobulin therapy tends to elicit varied therapeutic responses depending on the peripheral neuropathy phenotype. We also discuss myositis, a possible complication of Sjögren's syndrome.


Subject(s)
Peripheral Nervous System Diseases , Sjogren's Syndrome , Humans , Sjogren's Syndrome/complications , Peripheral Nervous System Diseases/etiology , Peripheral Nervous System Diseases/diagnosis , Muscular Diseases/etiology , Muscular Diseases/therapy , Diagnosis, Differential
14.
BMJ Case Rep ; 17(4)2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38684355

ABSTRACT

A female patient in her 70s with a newly diagnosed clear cell renal cell carcinoma (ccRCC) with osseous metastasis presented with sudden onset erythematous painful blistering skin lesions on the dorsum of both hands, with associated intermittent fever episodes. Blood tests showed elevated inflammatory marker levels (C reactive protein 257.8 mg/dL, leucocytes 17.79×109/L, with 94% neutrophils). Histologically, there was predominately neutrophil dermal infiltrate without leucocytoclastic vasculitis. The diagnostic criteria of Sweet syndrome were fulfilled. A week later, the patient developed abrupt left-hand palsy, which was confirmed as a medial and ulnar sensorimotor axonal peripheral neuropathy of paraneoplastic origin. The patient was prescribed a course of oral high-dose steroids, which significantly improved the skin lesions. The peripheral nerve palsy improved after 3 months. This case describes the two very rare concurrent paraneoplastic manifestations of ccRCC occurring simultaneously, which have been rarely reported.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Sweet Syndrome , Humans , Sweet Syndrome/diagnosis , Sweet Syndrome/drug therapy , Sweet Syndrome/complications , Carcinoma, Renal Cell/secondary , Carcinoma, Renal Cell/complications , Female , Kidney Neoplasms/pathology , Kidney Neoplasms/complications , Aged , Peripheral Nervous System Diseases/etiology , Peripheral Nervous System Diseases/diagnosis , Bone Neoplasms/secondary , Bone Neoplasms/complications
15.
Article in English | MEDLINE | ID: mdl-38681505

ABSTRACT

Background: Posterior interosseous neuropathy is an uncommon cause of peripheral dystonia. Case Report: A 62-year-old man awakened and noticed right finger drop. A neurological examination revealed posterior interosseous neuropathy with dystonia-like finger movements. Abnormal movements were predominantly observed in the right thumb, ring finger, and little finger. Within 2 weeks, the muscle weakness in the right fingers had completely improved. However, a brief abnormal posture of the right thumb was persistent. Discussion: The residual abnormal posture of the right thumb may reflect pre-existing motor control abnormalities, which may have contributed to the onset of posterior interosseous neuropathy-associated peripheral dystonia.


Subject(s)
Dystonia , Humans , Male , Middle Aged , Dystonia/physiopathology , Dystonia/etiology , Dystonic Disorders/physiopathology , Dystonic Disorders/complications , Dystonic Disorders/diagnosis , Peripheral Nervous System Diseases/physiopathology , Peripheral Nervous System Diseases/complications , Peripheral Nervous System Diseases/etiology , Peripheral Nervous System Diseases/diagnosis , Fingers/physiopathology
16.
Viruses ; 16(4)2024 03 28.
Article in English | MEDLINE | ID: mdl-38675865

ABSTRACT

Chronic hepatitis C virus (HCV) infection is characterized by a variety of extra-hepatic manifestations; peripheral neuropathy (PN) is one of the most common, especially when mixed cryoglobulinemia (MCG) is present. The prevalence and risk factors of HCV-related PN in the absence of MCG are largely unknown. We conducted a prospective, single-center study, examining the prevalence and reversibility of HCV-associated neuropathy in the absence of MCG. Nerve fiber density in the epidermis was evaluated through skin biopsy and electroneurography (ENG) before HCV-treatment initiation and 1 year post sustained virological remission (SVR). Forty HCV-infected individuals (nine HIV co-infected) with no other neuron-harming factors were included; four other HCV mono- and three HIV co-infected individuals were excluded due to presence of diabetes, B12 insufficiency, or neurotoxic drugs. Twelve consecutive controls with no neuron-harming conditions were also recruited; eight more were excluded due to meeting exclusion criteria. Four patients had ENG signs of polyneuropathy (two with HCV mono- and two with HIV co-infection), while seven more (five with HCV mono- and two with HIV co-infection) had signs of mono-neuropathy, leading to PN prevalences of 22.5% and 44% for mono- and co-infection, respectively (p value 0.179). The two patients with HCV mono-infection and polyneuropathy and the one with ulnar nerve damage showed ENG improvement 1 year post SVR. Regarding intraepidermal nerve density, HCV infection, irrespective of HIV co-infection, was correlated with a lower intraepidermal neuron density that improved 1 year post SVR (p value 0.0002 for HCV and 0.0326 for HCV/HIV co-infected patients). PN is common in HCV infection; successful eradication of HCV leads to PN improvement.


Subject(s)
Antiviral Agents , Hepatitis C, Chronic , Peripheral Nervous System Diseases , Humans , Male , Female , Middle Aged , Peripheral Nervous System Diseases/etiology , Peripheral Nervous System Diseases/virology , Prospective Studies , Antiviral Agents/therapeutic use , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/drug therapy , Adult , HIV Infections/complications , HIV Infections/drug therapy , Prevalence , Hepacivirus/drug effects , Aged , Coinfection/drug therapy , Coinfection/virology , Risk Factors , Cryoglobulinemia/etiology , Sustained Virologic Response
17.
Alcohol Alcohol ; 59(2)2024 Jan 17.
Article in English | MEDLINE | ID: mdl-38469882

ABSTRACT

AIMS: Chronic alcohol consumption is well known to cause peripheral neuropathy, affecting both small and large nerve fibers. The aim of this study was to correlate biochemical and neurophysiological findings and investigate possible biomarkers and risk factors for pathogenetic mechanisms of neuropathy in patients diagnosed with alcohol use disorder (AUD). METHODS: Ninety patients diagnosed with AUD were enrolled in this prospective study over a period of 3 years. Serum biochemical parameters, as well as thiamine blood levels, were determined upon admission. Every subject was assessed by clinical neurological examination, followed by Nerve Conduction Studies, Quantitative Sensory Testing, and Sympathetic Skin Response. Fifty age and gender-matched patients without a diagnosis of AUD were used as the control group. RESULTS: Peripheral neuropathy was diagnosed in 54 patients (60%). Among them, pure large fiber neuropathy was found in 18 patients, pure small fiber neuropathy in 12 patients, and both large and small fiber neuropathy was diagnosed in 24 patients. Elevated liver enzymes and fasting glucose levels upon admission were significantly correlated with neuropathy. Lower blood thiamine levels (than reference) were found in seven patients and were not correlated with neuropathy. CONCLUSIONS: Our study suggests that alcohol-related liver dysfunction and hyperglycemia may contribute as risk factors of peripheral neuropathy in patients diagnosed with AUD, while blood thiamine levels do not correlate with neuropathy. Moreover, we suggest that liver enzymes and the De Ritis ratio could be potentially used as biomarkers for the incidence and severity of alcohol-related neuropathy.


Subject(s)
Alcoholism , Liver Diseases , Peripheral Nervous System Diseases , Small Fiber Neuropathy , Humans , Thiamine , Alcoholism/complications , Alcoholism/diagnosis , Small Fiber Neuropathy/complications , Prospective Studies , Peripheral Nervous System Diseases/diagnosis , Peripheral Nervous System Diseases/etiology , Peripheral Nervous System Diseases/pathology , Alcohol Drinking/adverse effects , Liver Diseases/complications , Biomarkers , Fasting , Glucose
18.
Hemodial Int ; 28(2): 188-197, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38449056

ABSTRACT

BACKGROUND: Accelerated neuropathy is a rare syndrome of rapidly worsening peripheral neuropathy, typically described in end-stage kidney disease (ESKD) patients undergoing dialysis. In our center, we encountered a surge in the occurrence of accelerated neuropathy among ESKD patients undergoing hemodialysis, which prompted systematic research. METHODS: In this case-control study, we present the clinical features, electrophysiologic findings, and outcome of a series of patients who developed accelerated neuropathy after commencing hemodialysis for ESKD. Those who initiated hemodialysis and did not develop accelerated neuropathy were included as controls. We used logistic regression to identify predictors of accelerated neuropathy. RESULTS: Among 436 ESKD patients who initiated hemodialysis over 4 years, 17 were diagnosed with accelerated neuropathy. The median-time (interquartile range) from hemodialysis initiation to presentation with accelerated neuropathy was 3 weeks (2-6). It typically presented as acute onset of unsteadiness of gait necessitating assistance for ambulation. Electrophysiology revealed length-dependent symmetric sensorimotor axonal neuropathy. Diabetes mellitus (odds ratio [OR] 4.1, 95% CI 1.2-13.9, p = 0.02), pre-existing peripheral neuropathy (OR 9.25, 95% CI 2.79-30.6, p < 0.001), and serum alkaline phosphatase (OR 1.2 for every 10 U increase, 95% CI 1.00-1.52, p = 0.04) significantly predicted accelerated neuropathy. With continued dialysis and supportive care, neurologic status improved, total-neuropathy score (summary score of peripheral nerve dysfunction incorporating clinical and electrophysiological parameters) declined from 26.5 to 18.4 (p < 0.001) and most regained unassisted ambulation. CONCLUSION: This study presents the largest series of patients with accelerated neuropathy and has identified predictors. However, in view of the unusually high incidence of accelerated neuropathy we speculate that other unidentified factor(s) could be underlying its pathogenesis.


Subject(s)
Kidney Failure, Chronic , Peripheral Nervous System Diseases , Humans , Renal Dialysis/adverse effects , Case-Control Studies , Peripheral Nervous System Diseases/etiology , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapy
19.
Mol Ther ; 32(5): 1407-1424, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38429927

ABSTRACT

Maintaining functional adipose innervation is critical for metabolic health. We found that subcutaneous white adipose tissue (scWAT) undergoes peripheral neuropathy (PN) with obesity, diabetes, and aging (reduced small-fiber innervation and nerve/synaptic/growth-cone/vesicle markers, altered nerve activity). Unlike with nerve injuries, peripheral nerves do not regenerate with PN, and therefore new therapies are needed for treatment of this condition affecting 20-30 million Americans. Here, we validated a gene therapy approach using an adipocyte-tropic adeno-associated virus (AAV; serotype Rec2) to deliver neurotrophic factors (brain-derived neurotrophic factor [BDNF] and nerve growth factor [NGF]) directly to scWAT to improve tissue-specific PN as a proof-of-concept approach. AAVRec2-BDNF intra-adipose delivery improved tissue innervation in obese/diabetic mice with PN, but after longer periods of dietary obesity there was reduced efficacy, revealing a key time window for therapies. AAVRec2-NGF also increased scWAT innervation in obese mice and was more effective than BDNF, likely because Rec2 targeted adipocytes, the tissue's endogenous NGF source. AAVRec2-NGF also worked well even after 25 weeks of dietary obesity, unlike BDNF, which likely needs a vector that targets its physiological cellular source (stromal vascular fraction cells). Given the differing effects of AAVs carrying NGF versus BDNF, a combined therapy may be ideal for PN.


Subject(s)
Adipocytes , Brain-Derived Neurotrophic Factor , Dependovirus , Genetic Therapy , Genetic Vectors , Obesity , Subcutaneous Fat , Animals , Dependovirus/genetics , Obesity/therapy , Obesity/metabolism , Mice , Genetic Therapy/methods , Adipocytes/metabolism , Genetic Vectors/administration & dosage , Genetic Vectors/genetics , Subcutaneous Fat/metabolism , Brain-Derived Neurotrophic Factor/metabolism , Brain-Derived Neurotrophic Factor/genetics , Disease Models, Animal , Nerve Growth Factor/metabolism , Nerve Growth Factor/genetics , Nerve Growth Factors/metabolism , Nerve Growth Factors/genetics , Gene Transfer Techniques , Humans , Male , Peripheral Nervous System Diseases/therapy , Peripheral Nervous System Diseases/etiology , Peripheral Nervous System Diseases/metabolism , Peripheral Nervous System Diseases/genetics , Transduction, Genetic
SELECTION OF CITATIONS
SEARCH DETAIL