Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 132
Filtrar
1.
J Neuroimmunol ; 343: 577233, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32272393

RESUMO

BACKGROUND: GFAP (glial fibrillary acidic protein)-IgG is predominantly associated with meningoencephalomyelitis, and neuropathy presentations are rare. METHODS: We reviewed clinical, electrodiagnostic and histopathological presentations of GFAP-IgG associated peripheral neuropathy. RESULTS: We identified six cases, five of whom had peripheral neuropathy as the initial presentation. Acute/subacute polyradicluoneuropathy or proximal nerve involvement was a common presentation. Three had demyelinating neuropathies on electrophysiological studies. Nerve biopsies (n = 2) demonstrated T-cell predominant perivascular inflammatory collections, and all patients with clinical follow up responded favorably to immunotherapy. CONCLUSION: GFAP neuropathy represents a potentially treatable immune-mediated neuropathy and can occur with or without co-existing meningoencephalomyelitis.

2.
Neurology ; 94(12): e1314-e1319, 2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-31992683

RESUMO

OBJECTIVE: To investigate the following among patients with phrenic neuropathy: (1) occurrences of water immersion activity-induced dyspnea; (2) clinical, electrophysiologic, sonographic, and pulmonary function test abnormalities; and (3) frequency of documented counseling regarding the risks of water immersion activities. METHODS: We identified all patients with test-confirmed phrenic neuropathy seen from January 1, 2000, to December 31, 2018, at Mayo Clinic. RESULTS: Of 535 patients with phrenic neuropathy, documentation of dyspnea with water activities was identified in 4% (22/535). The risks of water immersion were only documented in patients having experienced this problem. The majority had isolated phrenic neuritis or neuralgic amyotrophy syndrome (77.3%), mean age was 55 years (range 31-79), and most patients were men (81.9%). Patients had right-sided (45.5%) or bilateral (54.5%) phrenic neuropathy. None had isolated left phrenic involvement. Near-fatal drowning occurred in 18.2% (4/22), with persons needing assistance to be rescued from the water, following diving into water. Dyspnea with water immersion was the only symptom in 4.5% (1/22) and the presenting respiratory symptom in 36.4% (8/22). A range of electrophysiologic, sonographic, and pulmonary function test abnormalities including mild abnormalities were seen and not found to be significantly different from those in patients in whom water-induced dyspnea was not recorded. CONCLUSION: Respiratory distress with water immersion activities is a serious complication of phrenic neuropathies. Physician-documented counseling is lacking. Isolated phrenic neuritis, neuralgic amyotrophy, and right-sided and bilateral phrenic involvement are most commonly implicated, but the range of severity and testing abnormalities suggest that all patients with neuralgic amyotrophy or phrenic neuropathy should be warned especially about diving into water.

3.
Ophthalmology ; 127(2): 221-229, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31676123

RESUMO

PURPOSE: Collapsin response-mediator protein 5 (CRMP5) immunoglobulin G (IgG) has been associated with paraneoplastic optic neuritis, vitritis, retinitis, or a combination thereof, but few reports of these findings exist in the literature. We reviewed the neuro-ophthalmic findings and visual outcomes in a large series of CRMP5 IgG-positive patients to characterize further its clinical phenotype and response to treatment. DESIGN: Retrospective case series. PARTICIPANTS: Seventy-six patients with CRMP5 autoimmunity examined at the Mayo Clinic, Rochester, Minnesota. METHODS: Single academic medical center chart review of all CRMP5 IgG-positive (serum titer, >1:240) patients seen between 2001 and 2017. MAIN OUTCOME MEASURES: Neuro-ophthalmic manifestations and outcomes of CRMP5 autoimmunity, coexisting neural autoantibody presence and paraneoplastic associations, and the impact of immunosuppressant therapy. RESULTS: Twenty-nine of 76 patients (38%) demonstrated neuro-ophthalmic manifestations. Of the 29 patients with neuro-ophthalmic findings, the median age was 67 years (range, 33-88 years) and 20 (69%) were women. Cancer was diagnosed in 62% of the patients (small-cell carcinoma in 83%). Neuro-ophthalmic symptoms occurred before the diagnosis of cancer in 72%. Seventeen of 29 patients (59%) showed ocular (i.e., anterior visual pathway or intraocular) manifestations; presenting median visual acuity was 20/50 (range, 20/20-counting fingers) and the final median visual acuity was 20/40 (range, 20/20-hand movements). Fourteen of 17 patients (82%) demonstrated optic neuropathy, with 12 of these patients also showing retinitis or uveitis. Three of 17 patients (18%) showed retinitis or uveitis without optic neuropathy. All 12 patients with optic neuropathy and a documented fundus examination at visual symptom onset demonstrated optic disc edema. No patients showed optic nerve enhancement on magnetic resonance imaging. Twelve of 29 patients (41%) demonstrated ocular motility dysfunction consisting of central nystagmus and diplopia. Among those receiving immunosuppressive therapy, visual function improved in 50%. CONCLUSIONS: In our cohort of 29 CRMP5 IgG-positive patients with neuro-ophthalmic manifestations, optic neuropathy presented with optic disc edema, often associated with uveitis, retinitis, or both. The combination of retinitis, vitritis, and optic disc edema without optic nerve enhancement should prompt serologic testing for CRMP5 IgG to expedite vision-sparing immunosuppressant therapy and a targeted search for a systemic cancer.

4.
J Neurol Neurosurg Psychiatry ; 91(2): 177-188, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30224548

RESUMO

The immune system has long been recognised important in pain regulation through inflammatory cytokine modulation of peripheral nociceptive fibres. Recently, cytokine interactions in brain and spinal cord glia as well as dorsal root ganglia satellite glia have been identified important- in pain modulation. The result of these interactions is central and peripheral sensitisation of nociceptive processing. Additionally, new insights and the term 'autoimmune pain' have emerged through discovery of specific IgGs targeting the extracellular domains of antigens at nodal and synaptic structures, causing pain directly without inflammation by enhancing neuronal excitability. Other discovered IgGs heighten pain indirectly by T-cell-mediated inflammation or destruction of targets within the nociceptive pathways. Notable identified IgGs in pain include those against the components of channels and receptors involved in inhibitory or excitatory somatosensory synapses or their pathways: nodal and paranodal proteins (LGI1, CASPR1, CASPR2); glutamate detection (AMPA-R); GABA regulation and release (GAD65, amphiphysin); glycine receptors (GLY-R); water channels (AQP4). These disorders have other neurological manifestations of central/peripheral hyperexcitabability including seizures, encephalopathy, myoclonus, tremor and spasticity, with immunotherapy responsiveness. Other pain disorders, like complex regional pain disorder, have been associated with IgGs against ß2-adrenergic receptor, muscarinic-2 receptors, AChR-nicotinic ganglionic α-3 receptors and calcium channels (N and P/Q types), but less consistently with immune treatment response. Here, we outline how the immune system contributes to development and regulation of pain, review specific IgG-mediated pain disorders and summarise recent development in therapy approaches. Biological agents to treat pain (anti-calcitonin gene-related peptide and anti-nerve growth factor) are also discussed.

5.
Neurology ; 93(20): e1873-e1880, 2019 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-31624089

RESUMO

OBJECTIVE: To define the clinicopathologic features of amphiphysin-immunoglobulin G (IgG)-mediated neuropathy. METHODS: Patients examined at our institution from January 1, 1995, to September 30, 2018, with amphiphysin-IgG by indirect immunofluorescence and Western blot, were reviewed. Their phenotypes were compared to cases of coexisting collapsin response-mediator protein-5 (CRMP5)-IgG or anti-neuronal nuclear antibody type 1 (ANNA1-IgG) and CRMP5-IgG autoimmunity. Improvement in modified Rankin Scale (mRS) (≥1) on follow-up was considered a favorable outcome. Amphiphysin RNA expression was assessed in healthy nerves. RESULTS: Fifty-three amphiphysin-IgG-positive cases were identified. Of 33 (60%) patients with neuropathy, 21 had amphiphysin-IgG alone, and 12 had coexisting autoantibodies (ANNA1-IgG, n = 8; CRMP5-IgG, n = 2; ANNA1-IgG and CRMP5-IgG, n = 2). The neuropathies in isolated amphiphysin-IgG autoimmunity included polyradiculoneuropathy (62%), diffuse sensory neuronopathy (35%), and facial neuropathy with gastroparesis (3%). Among these, pain (80%), breast cancer (63%), and CNS (57%) involvements commonly coexisted, and neuropathy frequently prompted breast cancer diagnosis (76%). Stiff-person spectrum disorder was the most common CNS accompaniment (45%). Nerve biopsies showed axonal loss (n = 6/6), subperineurial edema (n = 4/6), and CD4 predominant inflammation (n = 2/6). Median mRS score at last follow-up was 3.5; 58% of patients were immunotherapy-responsive. Patients with amphiphysin-IgG alone had more favorable immunotherapy response than patients with CRMP5-IgG polyneuropathy (n = 45) (44% vs 16%, p = 0.028, odds ratio 4.2, 95% confidence interval 1.1 to 15.5). Only 1/9 (11%) patients with amphiphysin-IgG with coexisting CRMP5-IgG or ANNA1-IgG had immunotherapy response. RNA amphiphysin expression occurred at low levels in nerve. CONCLUSION: Amphiphysin-IgG autoimmune neuropathy has a recognizable phenotype, is frequently immune responsive, and can prompt early diagnosis of breast cancer.


Assuntos
Autoanticorpos/imunologia , Doenças Autoimunes do Sistema Nervoso/imunologia , Proteínas do Tecido Nervoso/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antinucleares/imunologia , Doenças Autoimunes do Sistema Nervoso/epidemiologia , Doenças Autoimunes do Sistema Nervoso/patologia , Doenças Autoimunes do Sistema Nervoso/fisiopatologia , Biópsia , Neoplasias da Mama/epidemiologia , Comorbidade , Doenças do Nervo Facial/epidemiologia , Doenças do Nervo Facial/imunologia , Doenças do Nervo Facial/patologia , Doenças do Nervo Facial/fisiopatologia , Feminino , Humanos , Hidrolases/imunologia , Imunoglobulina G/imunologia , Masculino , Proteínas Associadas aos Microtúbulos/imunologia , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/genética , Dor , Nervos Periféricos/imunologia , Nervos Periféricos/metabolismo , Nervos Periféricos/patologia , Polirradiculoneuropatia/epidemiologia , Polirradiculoneuropatia/imunologia , Polirradiculoneuropatia/patologia , Polirradiculoneuropatia/fisiopatologia , Rigidez Muscular Espasmódica/epidemiologia , Síndrome
8.
Neurology ; 93(10): e954-e963, 2019 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-31371564

RESUMO

OBJECTIVE: To describe phenotypes, treatment response, and outcomes of autoimmunity targeting a synaptic vesicle coat protein, the neuronal (B2) form of adaptor protein-3 (AP3). METHODS: Archived serum and CSF specimens (from 616,025 screened) harboring unclassified synaptic antibodies mimicking amphiphysin-immunoglobulin G (IgG) on tissue-based indirect immunofluorescence assay (IFA) were re-evaluated for novel IgG staining patterns. Autoantigens were identified by western blot and mass spectrometry. Recombinant western blot and cell-binding assay (CBA) were used to confirm antigen specificity. Clinical data were obtained retrospectively. RESULTS: Serum (10) and CSF (6) specimens of 10 patients produced identical IFA staining patterns throughout mouse nervous system tissues, most prominently in cerebellum (Purkinje neuronal perikarya, granular layer synapses, and dentate regions), spinal cord gray matter, dorsal root ganglia, and sympathetic ganglia. The antigen revealed by mass spectrometry analysis and confirmed by recombinant assays (western blot and CBA) was AP3B2 in all. Of 10 seropositive patients, 6 were women; median symptom onset age was 42 years (range 24-58). Clinical information was available for 9 patients, all with subacute onset and rapidly progressive gait ataxia. Neurologic manifestations were myeloneuropathy (3), peripheral sensory neuropathy (2), cerebellar ataxia (2), and spinocerebellar ataxia (2). Five patients received immunotherapy; none improved, but they did not worsen over the follow-up period (median 36 months; range 3-94). Two patients (both with cancer) died. One of 50 control sera was positive by western blot only (but not by IFA or CBA). CONCLUSION: AP3B2 (previously named ß-neuronal adaptin-like protein) autoimmunity appears rare, is accompanied by ataxia (sensory or cerebellar), and is potentially treatable.


Assuntos
Complexo 3 de Proteínas Adaptadoras/metabolismo , Subunidades beta do Complexo de Proteínas Adaptadoras/metabolismo , Autoimunidade/fisiologia , Transtornos Neurológicos da Marcha/diagnóstico por imagem , Transtornos Neurológicos da Marcha/metabolismo , Imunoglobulina G/metabolismo , Adulto , Animais , Autoanticorpos/sangue , Autoanticorpos/líquido cefalorraquidiano , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Células Cultivadas , Ataxia Cerebelar/diagnóstico por imagem , Ataxia Cerebelar/metabolismo , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Ratos
9.
Epigenetics ; 14(9): 927-937, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31148524

RESUMO

Sensory neurons of the peripheral nervous system are critical in health and disease. Sensory neurons derived from induced pluripotent stem (iPS) cells are now being used increasingly for in vitro models of neuropathy, pain, and neurotoxicity. DNA methylation is critical for neurodevelopment and has been implicated in many neuronal diseases, but has not been examined in iPS-derived sensory neurons. In order to better characterize the iPS-derived sensory neuron model, we have undertaken a genome-wide DNA methylation study on the cells from human iPS to iPS-derived sensory neurons during differentiation through reduced representation and bisulfite sequencing. We report decreasing DNA methylation with iPS-derived sensory neuronal differentiation that is reflected in increasing numbers and proportions of hypomethylated individual CpGs and regions, as well as lowered DNMT3b expression. Furthermore, genes with changes in DNA methylation near their TSS suggest key pathways that may be involved in iPS-derived sensory neuronal differentiation. These findings provide insights into sensory neuronal differentiation and can be used for further in vitro modelling of disease states.

11.
Mult Scler Relat Disord ; 30: 284-290, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30870805

RESUMO

BACKGROUND: Polyneuropathies co-occurring with multiple sclerosis (MS) may be underdiagnosed while causing additional disability burden. OBJECTIVE: To determine polyneuropathy presence and type in MS and compare MS with chronic inflammatory demyelinating polyradiculoneuropathy (MS-CIDP) versus MS with other non-inflammatory polyneuropathies. METHODS: Retrospective chart review of Mayo Clinic cases diagnosed with MS and polyneuropathy. Serum from MS-CIDP for pan-IgG autoantibodies to neurofascin-155 were tested when available. RESULTS: From 1980-2013, 133 co-existing MS/ polyneuropathy cases were identified. Twenty-eight MS patients had inflammatory neuropathy (11 CIDP, 5 plexopathy, 2 vasculitis, 4 monoclonal gammopathy-associated, 6 other), 15 inherited neuropathy (8 axonal, 7 demyelinating), 32 diabetic sensorimotor polyneuropathy, and 58 other. 109 had neuropathy beginning simultaneous to or after MS diagnosis (82%). Compared to MS cases with other polyneuropathy subtypes, MS-CIDP cases had absent or reduced ankle reflexes (100 vs. 70%, p = 0.04), earlier age of neuropathy recognition (52 vs. 58 years, p = 0.048), worse impairment (NIS 27 vs. 22 points, p < 0.03), and more acquired demyelinating electrophysiology features (46% vs. 9%, p < 0.003). Of MS-CIDP cases with available serum, 1-in-3 had IgG4 autoantibodies to neurofascin-155. CONCLUSION: (1) Polyneuropathies occurring in MS contribute to neurological disability. (2) Diagnosing polyneuropathies in people with MS is challenging and, likely, under-diagnosed. Recognition is important as some polyneuropathies (e.g., CIDP) are treatable. (3) The probable over-representation of inflammatory neuropathy (especially CIDP) in MS suggests a shared dysimmune pathogenesis, supported by autoantibodies to neurofascin-155.


Assuntos
Esclerose Múltipla/complicações , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/etiologia , Adolescente , Adulto , Idoso , Moléculas de Adesão Celular/sangue , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/sangue , Esclerose Múltipla/patologia , Fibras Nervosas/metabolismo , Fibras Nervosas/patologia , Fatores de Crescimento Neural/sangue , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/patologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Adulto Jovem
12.
Muscle Nerve ; 59(6): 665-670, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30810227

RESUMO

INTRODUCTION: Onion-bulbs (OB) are concentrically layered Schwann-cell processes, surrounding nerve fibers, occurring in both inherited and acquired demyelinating polyneuropathies. We investigated whether OB patterns (generalized, mixed, or focal) correlate with acquired or inherited neuropathies. METHODS: One hundred thirty-one OB-rich nerve biopsies were graded for OB pattern and inflammation without knowledge of clinical history. We classified inherited (n = 49) or acquired (n = 82) neuropathies based solely on clinical history. RESULTS: Fifty-one biopsies had generalized (34 inherited vs. 17 acquired, P < 0.001), 54 mixed (48 acquired vs. 6 inherited, P < 0.001), and 26 focal/multifocal (inherited [n = 9], acquired [n = 17]) OB. Inflammation occurred more frequently in acquired (n = 54) than inherited (n = 14) neuropathy (P = 0.004). DISCUSSION: Generalized OB correlates with inherited neuropathy; mixed OB with acquired. Inflammation occurs more in acquired neuropathy cases. OB patterns are best explained by ubiquitous Schwann-cell involvement in inherited and multifocal Schwann-cell involvement in acquired neuropathies and predict the electrophysiology of uniform demyelination in inherited and unequal demyelination in acquired neuropathies. Muscle Nerve 59:665-670, 2019.


Assuntos
Neuropatia Hereditária Motora e Sensorial/patologia , Nervos Periféricos/patologia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/patologia , Células de Schwann/patologia , Adolescente , Adulto , Idoso , Biópsia , Doença de Charcot-Marie-Tooth/patologia , Feminino , Neuropatia Hereditária Motora e Sensorial/genética , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas da Mielina/genética , Adulto Jovem
13.
Adv Skin Wound Care ; 32(4): 168-175, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30624254

RESUMO

OBJECTIVE: To evaluate the associated diseases, polyneuropathy correlates, and risk covariates of neuropathic plantar ulcers (PUs) and neuropathic arthropathies (NAs). DESIGN: The authors conducted a retrospective, observational study over 3.5 years of 69 patients with neuropathy, NA, or PU seen in a wound clinic who also had a comprehensive neurologic evaluation and neurophysiologic testing. Comparisons were made to a population representative cohort of patients with diabetes mellitus (DM; n = 259). RESULTS: Of the 69 wound clinic patients, 32 had PUs, 14 had NAs, and 23 had both. Of the 61 adequately assessed patients, 37 (61%) had DM, 22 (36%) had no known associated disease, and 2 (3%) had hereditary sensory and autonomic neuropathy. Of the 37 patients with DM, 35 had distal polyneuropathy, and 2 did not. In 22 patients with chronic idiopathic axonal polyneuropathy, 20 had distal polyneuropathy. CONCLUSIONS: Although DM was the disease most commonly associated with PUs and NAs, chronic hyperglycemia may not have been the major underlying risk factor. The major risk covariates are sensation loss from polyneuropathy, old age, obesity, repetitive foot injury, and inadequate foot care or treatment. Physicians and other healthcare providers can help by identifying patients at risk and instituting measures such as adequate foot care to decrease these risks.


Assuntos
Artropatia Neurogênica/epidemiologia , Úlcera do Pé/epidemiologia , Placa Plantar/fisiopatologia , Polineuropatias/epidemiologia , Cicatrização/fisiologia , Distribuição por Idade , Idoso , Artropatia Neurogênica/diagnóstico , Estudos de Coortes , Comorbidade , Progressão da Doença , Feminino , Úlcera do Pé/diagnóstico , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Polineuropatias/diagnóstico , Prognóstico , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Distribuição por Sexo
14.
Neuromuscul Disord ; 29(2): 146-149, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30658899

RESUMO

X-linked adrenoleukodystrophy is a peroxisomal disorder caused by a mutation in ABCD1 gene. The three main phenotypes of X-linked adrenoleukodystrophy include cerebral adrenoleukodystrophy, adrenomyeloneuropathy, and isolated primary adrenal insufficiency. More than 750 non-recurrent mutations exist throughout the coding region of the ABCD1 gene. We report a 62-year-old man with a 17-year history of progressive gait imbalance and numb feet. He had noted difficulty rising from a chair for 3 years. Examination revealed proximal lower limb weakness and length-dependent sensory loss with preservation of reflexes and unilateral Babinski sign. Electrodiagnostic evaluation confirmed a length-dependent sensorimotor peripheral neuropathy and proximal myopathy. Family history was remarkable for similar symptoms in 6 siblings. A targeted gene approach for 102 known peripheral neuropathy genes led to discovery of ABCD1 mutation confirmed by kindred evaluation and biochemical assay. This case highlights the importance of combining targeted gene approaches with functional assay confirmation especially for atypical clinical presentations.

15.
J Neurol Neurosurg Psychiatry ; 90(2): 138-140, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30385486

RESUMO

OBJECTIVE: To describe an expanded teased nerve fibre classification in disease association. METHODS: We reviewed four newly proposed teased nerve fibre types (Types J-M): Type J, rope-like fibres; K, fibril-like clumps of osmium positivity; L, cellular debris along and within nerve fibres; M, circular axonal inclusions surrounded by thin myelin. Different clinical pathological entities were studied for these fibre types including chronic inflammatory demyelinating polyradiculoneuropathy (CIDP: N=20); amyloid polyneuropathy (N=20); intraneural B-cell lymphoma (N=20) or adult-onset polyglucosan body disease (APBD: N=6) in comparison with 112 disease controls. Student's t-test was used to test significance of association between the identified fibre types and the specific clinical diagnosis. RESULTS: Each fibre type significantly associated (p<0.001) with particular disease categories: Type J, 60% of CIDP cases; Type K, 75% of amyloid cases; Type L, 75% of intraneural lymphoma cases; Type M, 100% of APBD cases. Rarely were these fibres found in the other disease control cases ≤3% of cases. In three cases, the teased fibre findings were so striking additional paraffin nerve preparations were made to make the pathological diagnosis when initial paraffin sections were non-diagnostic. CONCLUSIONS: Teased nerve fibre Types J-M associate with commonly seen pathological diagnosis and are helpful in the consideration of specific neuropathy diagnoses.


Assuntos
Neuropatias Amiloides/patologia , Doença de Depósito de Glicogênio/patologia , Linfoma de Células B/patologia , Fibras Nervosas/patologia , Doenças do Sistema Nervoso/patologia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/patologia , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
16.
Mayo Clin Proc Innov Qual Outcomes ; 2(4): 382-386, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30560241

RESUMO

We describe a 51-year-old woman who over 5 years had 9 painful monophasic attacks affecting the brachial plexus before a fascicular plexus biopsy diagnosed large B-cell lymphoma. The initial attacks were responsive to steroids with clinical resolution. At last attack, magnetic resonance imaging showed multifocal T2 hyperintensities and nodular gadolinium enhancement in the right brachial plexus not seen previously. Also seen were similar changes in the thoracic spinal cord, basal ganglia, cerebellum, and brainstem. Positron emission tomography revealed marked hypermetabolic activity of the plexus facilitating targeted fascicular brachial plexus biopsy, making the pathological diagnosis. Neurolymphomatosis affecting the peripheral nervous system typically presents with insidious painful progressive infiltration of nerves, roots, or plexi. Recurrent idiopathic brachial neuritis attacks (ie, Parsonage-Turner syndrome) in contrast most commonly are seen in persons with a family history and a discoverable genetic cause by SEPT9 mutations, which tested negative in this patient. This case illustrates how neurolymphomatosis, which represents a malignant transformation of B cells within peripheral nerves, can sometimes present with paraneoplastic immune-responsive neuritis mimicking Parsonage-Turner syndrome. Recurrence, an immune-refractory course or insidious progressive involvement of the nervous system, should raise suspicion of neurolymphomatosis.

17.
Am J Surg Pathol ; 42(12): 1708-1714, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30303818

RESUMO

Perineuriomas are rare nerve sheath tumors, divided into intraneural and extraneural (soft tissue) types. Intraneural perineuriomas frequently contain TRAF7 mutations, and rarely, chr22q12 deletions. While chr22q losses can occur in soft tissue perineuriomas, comprehensive high-resolution molecular profiling has not been reported in these tumors and TRAF7 status is unknown. We used whole-exome sequencing and OncoScan single nucleotide polymorphism (SNP) array to evaluate 14 soft tissue perineuriomas. Thirteen cases showed 2 or more chromosomal abnormalities, composed primarily of large deletions. Recurrent chr22q deletions, containing the NF2 locus (n=6) and the previously unreported finding of chr17q deletions, with the NF1 locus (n=4) were frequent events and were mutually exclusive in all but1 case. In addition, 5 cases had varying chr2 deletions; and 4 cases had chr6 deletions. A chr10 deletion (previously reported in the sclerosing variant of soft tissue perineurioma) was observed in one case and another case had chr7 chromothripsis as the sole chromosomal abnormality. No TRAF7 mutations or alterations were identified in any case and no other evaluated gene (MAF<0.0001) had recurrent, deleterious mutations in >2 cases. The molecular genetic profiles showed no association with patient sex, age, tumoral histology or anatomic site. OncoScan SNP array analysis was performed on 10 cases and showed high concordance with the whole exome data, validating the large-scale deletions, duplications, and chr7 chromothripsis findings. In soft tissue perineuriomas, recurrent 22q12 deletions (with NF2) and 17q11 deletions (with NF1) appear to be mutually exclusive events, and alterations in NF1 or NF2 likely contribute to perineurioma pathogenesis, similar to other nerve sheath tumors. Moreover, the lack of TRAF7 mutations in soft tissue perineuriomas indicates divergent pathogenetic mechanisms from those of intraneural perineuriomas.


Assuntos
Biomarcadores Tumorais/genética , Deleção Cromossômica , Cromotripsia , Neoplasias da Bainha Neural/genética , Mutação Puntual , Polimorfismo de Nucleotídeo Único , Neoplasias de Tecidos Moles/genética , Adulto , Idoso de 80 Anos ou mais , Criança , Análise Mutacional de DNA/métodos , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Bainha Neural/patologia , Neurofibromina 1/genética , Neurofibromina 2 , Análise de Sequência com Séries de Oligonucleotídeos , Fenótipo , Neoplasias de Tecidos Moles/patologia , Transcriptoma , Peptídeos e Proteínas Associados a Receptores de Fatores de Necrose Tumoral/genética , Sequenciamento Completo do Exoma , Adulto Jovem
18.
J Neuroimmunol ; 323: 62-72, 2018 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-30196836

RESUMO

Recognition of autoimmunity as a cause of encephalopathy has increased. Recent studies have validated the use of Antibody-Prevalence-in-Epilepsy (APE) and Responsive-to-immunotherapy-in-Epilepsy (RITE) scores in the evaluation and management of autoimmune-epilepsy. We aim to assess the utility of these models for patients with cognitive dysfunction. Among the evaluated patients, 17% had antibodies universally associated with autoimmune-encephalopathy. NMDA-R-IgG and LGI1-IgG were the most common antibody specificities. Antibody-Prevalence-in-Epilepsy-and-Encephalopathy (APE2) score ≥ 4 was 99% sensitive and 93% specific for neural-specific-antibodies. Responsive-to-immunotherapy-in-Epilepsy-and-Encephalopathy (RITE2) score ≥ 7 had 96% sensitivity and 86% specificity for favorable initial immunotherapy response. Application of these models may optimize autoantibody evaluations and immunotherapeutic trials.


Assuntos
Autoanticorpos/sangue , Disfunção Cognitiva/sangue , Encefalite/sangue , Epilepsia/sangue , Doença de Hashimoto/sangue , Imunoterapia/tendências , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/terapia , Encefalite/diagnóstico por imagem , Encefalite/terapia , Epilepsia/diagnóstico por imagem , Epilepsia/terapia , Feminino , Células HEK293 , Doença de Hashimoto/diagnóstico por imagem , Doença de Hashimoto/terapia , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Receptores de N-Metil-D-Aspartato/sangue , Adulto Jovem
19.
Epilepsia Open ; 3(3): 348-356, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30187005

RESUMO

Objective: To characterize seizure semiology and the utility of antiepileptic drug (AED) therapy in leucine-rich glioma inactivated-1 ( LGI1-Ab) autoimmune epilepsy (AE). Methods: Patients with voltage-gated potassium channel complex (VGKCc) titers higher than 0.02 nmol/L who were evaluated between May 2008 and June 2016 at the 3 Mayo Clinic sites (Arizona, Florida, or Minnesota) were identified. We then performed a retrospective review of those who were LGI1-Ab positive and were treated for seizures. Results: A total of 1,095 patients with VGKCc titers higher than 0.02 nmol/L were identified, in which 77 were LGI1 positive. Of these, 56 patients with seizures were included in the analysis. Mean age at symptom onset was 62.9 years; 66% (n = 37) were male. The most common seizure semiology was focal faciobrachial dystonic seizures with preserved awareness (FBDS) (n = 35, 63%), followed by focal with impaired awareness (FIA) (n = 29, 52%), generalized tonic-clonic (GTCs) (n = 28, 50%), and focal non-motor seizures with preserved awareness (n = 28, 50%). The majority had more than one seizure type (n = 49, 88%; median = 2.5). Thirty-eight patients (68%) became seizure free: 29 (76%) with immunotherapy, 3 (5%) with AEDs alone, 2 (3%) with AEDs before any immunotherapy, and 4 (7%) with AEDs after immunotherapy. Levetiracetam (n = 47, 84%) and valproic acid (n = 21, 38%) were the most commonly used AEDs, but neither were associated with seizure freedom. Sodium channel blocking (NCB) AEDs were associated with seizure freedom in 4 patients compared to none treated with non-NCB AEDs. Regardless of class, AEDs prior to or apart from immunotherapy were associated with seizure freedom in only five patients (9%). In patients with FBDS, seizure freedom was more often associated with immunotherapy than AEDs (20/30 vs. 3/34, p = 0.001). Significance: Although FBDS are the most characteristic seizure type seen in LGI1-Ab AE, other seizure types including FIA and GTCs also occur. Immunotherapy was the treatment most frequently associated with seizure freedom in LGI1-Ab AE. In general, AEDs seemed to confer a very low chance for seizure freedom, although AEDs with NCB-blocking properties were associated with seizure freedom in a limited number. Levetiracetam in particular appears to be ineffective in this patient population.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA