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BACKGROUND: Disturbed sleep and its impact on quality of life (QoL) are underrecognized in myasthenia gravis (MG). AIMS: To evaluate the quality of sleep in MG using standard sleep questionnaires and assess factors that determine sleep. SETTINGS AND DESIGN: Prospective, cross-sectional, hospital-based study. PATIENTS AND METHODS: Fifty patients on stable drug therapy for at least 1 month and age- and gender-matched controls were assessed using standard sleep questionnaires [Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), and NIMHANS Comprehensive Sleep Disorders Questionnaire (NCSDQ)]. RESULTS: Myasthenia Gravis Foundation of America (MGFA) grade was I, IIA, IIB, IIIA, IIIB, and IVA in 11, 19, 3, 10, 6, and 1 respectively. The mean PSQI and ESS scores were similar in patients and controls. Patients with abnormal ESS (>10) were older and had greater neck circumference (P = 0.018 and <0.001). Body mass index was greater in patients with PSQI > 5 (P < 0.05). Age, gender, and clinical severity did not affect PSQI. Compared with ESS and PSQI, NCSDQ showed higher frequency of disturbed sleep, snoring, early morning headache, difficulty in initiation, and maintenance of sleep in MG, although the differences between patients and controls were not significant. No correlation was found between QoL and ESS or PSQI. CONCLUSION: Patients of MG with stable clinical course with adequate treatment have sleep quality comparable with healthy controls. Longitudinal assessment of sleep quality at multiple time points throughout the disease course and correlating with cross-sectional disease severity may further delineate the impact of disease on sleep and QoL.
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Miastenia Gravis , Calidad de Vida , Trastornos del Sueño-Vigilia , Humanos , Miastenia Gravis/complicaciones , Miastenia Gravis/diagnóstico , Miastenia Gravis/fisiopatología , Masculino , Femenino , Estudios Transversales , Persona de Mediana Edad , Encuestas y Cuestionarios , Adulto , Trastornos del Sueño-Vigilia/etiología , Estudios Prospectivos , Calidad del Sueño , Sueño/fisiología , AncianoRESUMEN
Tropical ataxic neuropathy (TAN) is characterised by ataxic polyneuropathy, degeneration of the posterior columns and pyramidal tracts, optic atrophy, and sensorineural hearing loss. It has been attributed to nutritional/toxic etiologies, but evidence for the same has been equivocal. TAN shares common clinical features with inherited neuropathies and mitochondrial disorders, it may be hypothesised that genetic abnormalities may underlie the pathophysiology of TAN. This study aimed to establish evidence for mitochondrial dysfunction by adopting an integrated biochemical and multipronged genetic analysis. Patients (n = 65) with chronic progressive ataxic neuropathy with involvement of visual and/or auditory pathways underwent deep phenotyping, genetic studies including mitochondrial DNA (mtDNA) deletion analysis, mtDNA and clinical exome sequencing (CES), and respiratory chain complex (RCC) assay. The phenotypic characteristics included dysfunction of visual (n = 14), auditory (n = 12) and visual + auditory pathways (n = 29). Reduced RCC activity was present in 13 patients. Mitochondrial DNA deletions were noted in five patients. Sequencing of mtDNA (n = 45) identified a homoplasmic variant (MT-ND6) and a heteroplasmic variant (MT-COI) in one patient each. CES (n = 45) revealed 55 variants in nuclear genes that are associated with neuropathy (n = 27), deafness (n = 7), ataxia (n = 4), and mitochondrial phenotypes (n = 5) in 36 patients. This study provides preliminary evidence that TAN is associated with a spectrum of genetic abnormalities, including those associated with mitochondrial dysfunction, which is in contradistinction from the prevailing hypothesis that TAN is related to dietary toxins. Analysing the functional relevance of these genetic variants may improve the understanding of the pathogenesis of TAN.
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Ataxia , ADN Mitocondrial , Humanos , Masculino , Femenino , ADN Mitocondrial/genética , Adulto , Persona de Mediana Edad , Ataxia/genética , Adolescente , Enfermedades Mitocondriales/genética , Adulto Joven , Mitocondrias/genética , Niño , Anciano , Secuenciación del Exoma , FenotipoRESUMEN
BACKGROUND: Peripheral neuropathy is one of the manifestations of primary or familial amyloidosis. Published studies from India are limited. MATERIALS AND METHODS: We reviewed the clinical and pathological features of amyloid neuropathy diagnosed at our Institute over the last 39 years. RESULTS: Fifty-five cases of amyloid neuropathies were diagnosed between 1981 and 2019, constituting 0.28% of peripheral nerve biopsies (55/19,081). Age at presentation ranged from 24 to 81 years (mean-48 years) with male preponderance [M:F = 3.58:1]. Duration of symptoms at presentation varied from 3 months to 10 years (mean-2.31 years). Majority presented with small fiber neuropathy (85%). Pure sensory symptoms predominated in 23%, while 72% had sensorimotor neuropathy and 35.8% had autonomic involvement, with isolated autonomic failure in one patient. Amyloid neuropathy was clinically suspected in 22.6% of nonfamilial cases. Familial amyloid neuropathy was suspected in eight patients. Genetic testing detected ATTR and gelsolin mutation in one each of tested patients. Nerve biopsies revealed characteristic birefringent amyloid deposits stained mahogany brown by Congo red predominantly surrounding endoneurial microvessels (34.5%), also in perineurium and epineurium in 25.45% cases. Preferential loss of small diameter myelinated fibers was noted. Axonal degeneration or regeneration was conspicuously absent. CONCLUSION: Amyloid neuropathy is uncommon (0.28% of nerve biopsies in our series). Nerve biopsy is essential for the diagnosis. We report our experience of amyloid neuropathy and underscore the importance of making an assiduous search for amyloid deposits in the appropriate setting. Awareness of this entity is important for early diagnosis in the light of emerging therapeutic advances.
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Neuropatías Amiloides , Humanos , Masculino , Persona de Mediana Edad , Femenino , Adulto , Anciano , Neuropatías Amiloides/patología , Neuropatías Amiloides/diagnóstico , Anciano de 80 o más Años , Adulto Joven , Neuropatías Amiloides Familiares/patología , Neuropatías Amiloides Familiares/genética , India , BiopsiaRESUMEN
Guillain-Barre syndrome (GBS) is the commonest cause of acute polyradiculoneuropathy that requires hospitalization. Many of these patients experience systemic and disease-related complications during its course. Notable among them is hyponatremia. Though recognized for decades, the precise incidence, prevalence, and mechanism of hyponatremia in GBS are not well known. Hyponatremia in GBS patients is associated with more severe in-hospital disease course, prolonged hospitalization, higher mortality, increased costs, and a greater number of other complications in the hospital and worse functional status at 6 months and at 1 year. Though there are several reports of low sodium associated with GBS, many have not included the exact temporal relationship of sodium or its serial values during GBS thereby underestimating the exact incidence, prevalence, and magnitude of the problem. Early detection, close monitoring, and better understanding of the pathophysiology of hyponatremia have therapeutic implications. We review the complexities of the relationship between hyponatremia and GBS with regard to its pathophysiology and treatment.
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Background: SH3TC2 variations lead to demyelinating recessive Charcot-Marie-Tooth (CMT) disease, which is commonly associated with early-onset scoliosis and cranial neuropathy. Data from Indian ethnicity is limited. Objective: We aim to report the characteristics of patients with SH3TC2-associated neuropathy from an Indian cohort. Patients and Methods: Data of five unrelated subjects with SH3TC2 variations were analyzed. Results: Clinical features included female predominance (n = 4), early-onset neuropathy (n = 2), pes cavus and hammer toes (n = 4), kyphoscoliosis (n = 1), impaired vision and hearing (n = 1), facial muscle weakness (n = 1), impaired kinaesthetic sense (n = 3), tremor (n = 2), and ataxia (n = 1). Four patients had the "CMT" phenotype, while one patient had Roussy-Levy syndrome. All had demyelinating electrophysiology with conduction velocities being "very slow" in one, "slow" in one, "mildly slow" in two, and "intermediate" in one patient. Brain stem auditory evoked potentials were universally abnormal though only one patient had symptomatic deafness. Seven variants were identified in SH3TC2 [homozygous = 3 (c.1412del, c.69del, c.3152G>A), heterozygous = 4 (c.1105C>T, c.3511C>T, c.2028G>C, c.254A>T)]. Except for c.3511C>T variant, the rest were novel. Three patients had additional variations in genes having pathobiological relevance in other CMTs or amyotrophic lateral sclerosis. Conclusion: We provide data on a cohort of patients of Indian origin with SH3TC2 variations and highlight differences from other cohorts. Though the majority were not symptomatic for hearing impairment, evoked potentials disclosed abnormalities in all. Further studies are required to establish the functional consequences of novel variants and their interacting molecular partners identified in the present study to strengthen their association with the phenotype.
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Enfermedad de Charcot-Marie-Tooth , Péptidos y Proteínas de Señalización Intracelular , Humanos , Femenino , Masculino , Péptidos y Proteínas de Señalización Intracelular/genética , Mutación , Fenotipo , Enfermedad de Charcot-Marie-Tooth/genética , Fenómenos ElectrofisiológicosRESUMEN
Background: Sensory nerve conduction parameters in Guillain Barre Syndrome (GBS) are underemphasized. Objective: To describe abnormalities on sensory conduction studies in a large cohort of prospectively evaluated patients of GBS and to correlate with clinico-electrophysiological features. Methods and Materials: Sensory conduction parameters of three nerves (median, ulnar, and sural) were analyzed using standard protocols in 238 patients (M: F 163:75, mean age: 35.76 ± 15.9 years). Electrophysiological subtyping was based on criteria of Hadden et al., and Rajabally et al. Results: Among patients with "typical" GBS who underwent electrophysiological testing within 30 days of symptom-onset (n = 219), 183 (83.5%) had abnormal sensory potentials (one nerve = 52, two nerves = 77, all three nerves = 54). Frequency of abnormalities in sensory potentials increased with duration of illness. Commonest abnormality was reduced amplitude or in-excitable nerves. Mean amplitude and velocity of median and ulnar nerve sensory potentials were significantly lower among those with demyelinating electrophysiology (P < 0.05). Proportion of subjects with reduced amplitude and velocity of median and ulnar nerve sensory potentials was higher among those who required mechanical ventilation (P < 0.05). Frequency of "sural sparing" ranged from 10.5% to 84.5% depending on the criteria used and almost always was significantly associated with demyelinating neuropathy. Conclusion: This prospective study provides comprehensive data on sensory conduction parameters in GBS. Abnormalities are frequent and vary with duration of illness. While median nerve is most frequently and more severely affected, involvement of sural nerve may have prognostic value.
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Síndrome de Guillain-Barré , Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , Estudios Prospectivos , Nervio Sural , Conducción Nerviosa/fisiología , Respiración ArtificialRESUMEN
Background: Myasthenia gravis (MG) is an immune-mediated disorder of the neuromuscular junction. About 10% are refractory to immunosuppressive therapy. Aims: To analyze the response of patients with generalized MG to rituximab. Methods and Materials: A retrospective review of patients with MG who received rituximab was carried out (n = 13, M:F = 6:7, mean age: 44.84 ± 15.73 years). Myasthenia Gravis Foundation of America (MGFA), MGFA post-intervention status (MGFA-PIS), and Myasthenia Gravis Status and Treatment Intensity (MGSTI) were assessed before and after rituximab. Results: The duration of MG was 104.07 ± 92.25 months. Before rituximab, the MGFA was IIA/IIB/IIIA/IIIB/IVB/V in 1/1/2/6/2/1 patients and MGSTI was four in eight patients and six in three patients. The mean duration of follow up was 20.92 ± 14.06 months (range, 4 to 42 months). Dose reduction or discontinuation of cholinesterase inhibitors could be achieved 12 patients. Complete stable remission (CSR) and pharmacologic remission (PR) were achieved in one and four patients respectively and five patients had minimal manifestations. Most patients attained level 0, 1 or 2 MGSTI at last follow up. No rituximab infusion-related adverse events were noted. Three patients had exacerbation of MG between one to five weeks after rituximab administration. Three patients died, one each due to a cardiac event unrelated to MG or treatment, complications related to myasthenic crisis, and coronavirus disease. Conclusions: Rituximab was effective in bringing about remission in MG and can be considered as a first-line agent. However, it has to be administered under close supervision as some patients develop exacerbation of MG akin to steroid-induced worsening.
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Países en Desarrollo , Miastenia Gravis , Humanos , Adulto , Persona de Mediana Edad , Rituximab/uso terapéutico , Resultado del Tratamiento , Miastenia Gravis/tratamiento farmacológico , Estudios RetrospectivosRESUMEN
Background and Aims: Guillain-Barré Syndrome (GBS), an immune-mediated neuropathy, is characterized by antibodies against gangliosides/ganglioside complexes (GSCs) of peripheral nerves. Antecedent infections have been reported to induce antibodies that cross-react with the host gangliosides and thereby have a pivotal role in conferring an increased risk for developing GBS. Data pertaining to the impact of various antecedent infections, particularly those prevalent in tropical countries like India on the ganglioside/GSC antibodies is sparse. We aimed at exploring the association between six antecedent infections and the profile of ganglioside/GSC antibodies in GBS. Methods: Patients with GBS (n = 150) and healthy controls (n = 50) were examined for the serum profile of antibodies against GM1, GM2, GD1a, GD1b, GT1b, and GQ1b and their GSCs by ELISA. These antibodies were correlated with immunoreactivities against Campylobacter jejuni, Japanese encephalitis (JE), dengue, influenza, zika, and chikungunya infections. Results: The frequencies of antibodies against six single gangliosides (P < 0.001) and their GSCs (P = 0.039) were significantly higher in patients as compared to controls. Except for GT1b-antibody which was more frequent in axonal GBS, none of the other ganglioside/GSC antibodies correlated with the electrophysiological subtypes of GBS. Antecedent JE infection was significantly associated with increased frequency of antibodies against GD1a, GD1b, GT1b, and GQ1b. Antibodies against GSCs were not influenced by the antecedent infections. Interpretation: This study for the first time shows an association between antecedent JE infection and ganglioside antibodies in GBS. This finding reinforces the determining role of antecedent infections on ganglioside antibody responses and the subsequent immunological processes in GBS.
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Background and Objectives: Charcot-Marie-Tooth (CMT) disease is the commonest inherited neuromuscular disorder and has heterogeneous manifestations. Data regarding genetic basis of CMT from India is limited. This study aims to report the variations by using high throughput sequencing in Indian CMT cohort. Methods: Fifty-five probands (M:F 29:26) with suspected inherited neuropathy underwent genetic testing (whole exome: 31, clinical exome: 17 and targeted panel: 7). Their clinical and genetic data were analysed. Results: Age at onset ranged from infancy to 54 years. Clinical features included early-onset neuropathy (n=23), skeletal deformities (n=45), impaired vision (n=8), impaired hearing (n=6), facial palsy (n=8), thickened nerves (n=4), impaired cognition (n=5), seizures (n=5), pyramidal signs (n=7), ataxia (n=8) and vocal cord palsy, slow tongue movements and psychosis in one patient each. Twenty-eight patients had demyelinating electrophysiology. Abnormal visual and auditory evoked potentials were noted in 60.60% and 37.5% respectively. Sixty two variants were identified in 37 genes including variants of uncertain significance (n=34) and novel variants (n=45). Eleven patients had additional variations in genes implicated in CMTs/ other neurological disorders. Ten patients did not have variations in neuropathy associated genes, but had variations in genes implicated in other neurological disorders. In seven patients, no variations were detected. Conclusion: In this single centre cohort study from India, genetic diagnosis could be established in 87% of patients with inherited neuropathy. The identified spectrum of genetic variations adds to the pool of existing data and provides a platform for validation studies in cell culture or animal model systems.
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The Hereditary Spastic Paraplegias (HSPs) are a group of clinically and genetically heterogeneous disorders characterized by length dependent degeneration of the corticospinal tracts. Genetic data related to HSPs are limited from India. We aimed to comprehensively analyse the phenotypic characteristics and genetic basis of a large cohort of HSP from India. Patients with HSP phenotype were evaluated for their clinical features, electrophysiological and radiological abnormalities. Genetic analyses were carried out by clinical exome sequencing (n = 52) and targeted sequencing (n = 5). The cohort comprised of 57 probands (M:F 40:17, age: 3.5-49 years). Based on the phenotype, the cohort could be categorized as 'pure' (n = 15, 26.3%) and 'complicated' (n = 42, 73.7%) HSP. Brain MRI showed thin corpus callosum (n = 10), periventricular hyperintensities (n = 20), cerebral atrophy (n = 3), cerebellar atrophy (n = 3) and diffuse atrophy (n = 4). Sixty-seven variants representing 40 genes were identified including 47 novel variants. Forty-eight patients (84.2%) had variants in genes previously implicated in HSP and other spastic paraplegia syndromes (SPG genes = 24, non-SPG genes = 24); among these 13 had variations in more than one gene and 12 patients (21.0%) had variations in genes implicated in potentially treatable/modifiable metabolic disorders (MTHFR = 8, MTRR = 1, ARG1 = 2 and ABCD1 = 1). In nine patients, no genetic variants implicated in spastic paraplegia phenotype were identified. Thus, the present study from India highlights the phenotypic complexities and spectrum of genetic variations in patients with HSP including those implicated in metabolically modifiable disorders. It sets a platform for carrying out functional studies to validate the causal role of the novel variants and variants of uncertain significance.
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Paraplejía Espástica Hereditaria , Atrofia , Perfil Genético , Humanos , Mutación , Paraplejía , Fenotipo , Paraplejía Espástica Hereditaria/genéticaRESUMEN
BACKGROUND: The IL-33/ST2 immune axis plays crucial roles in infection and immunity. A dysregulated IL-33/ST2 axis can induce autoimmune reaction and inflammatory responses. Guillain-Barré syndrome (GBS) is an acute peripheral neuropathy, mostly caused by post-infection autoimmunity. The role of IL-33/ST2 axis is not known in GBS. This study aimed to explore the role of IL-33/ST2 axis in GBS. METHODS: Three single nucleotide polymorphisms (SNPs) of Il33 gene (rs16924159, rs7044343, rs1342336) and three SNPs of Il1rl1 gene (rs10192157, rs1041973, rs10206753) coding for suppressor of tumorigenicity 2 (ST2) were genotyped in 179 GBS patients and 186 healthy controls by TaqMan Allelic Discrimination Assay. Plasma levels of IL-33 and sST2 were measured in a subset of GBS patients (n = 80) and healthy controls (n = 80) by ELISA. RESULTS: The frequencies of CC genotype of rs10192157 (p = 0.043) and TT genotype of rs10206753 (p = 0.036) SNPs of Il1rl1 gene differed significantly between GBS patients and healthy controls. Gene-gene interaction between Il33 and Il1rl1 genes also conferred significant risk for GBS. In addition, the plasma sST2 levels were significantly elevated in GBS patients compared to healthy subjects (24,934.31 ± 1.81 pg/ml vs. 12,518.97 ± 1.51 pg/ml, p < 0.001). Plasma sST2 levels showed a significant correlation with the disability scores at the peak of neurological deficit in GBS patients. CONCLUSIONS: The IL-33/ST2 axis is suggested to influence the immunopathogenesis of GBS. Genetic variants of Il1rl1 gene might serve as a risk determinant of GBS and plasma sST2 levels might emerge as a biomarker of severity of GBS, if replicated further by other studies.
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Síndrome de Guillain-Barré , Proteína 1 Similar al Receptor de Interleucina-1 , Interleucina-33 , Genotipo , Síndrome de Guillain-Barré/inmunología , Humanos , Proteína 1 Similar al Receptor de Interleucina-1/genética , Interleucina-33/genética , Polimorfismo de Nucleótido SimpleRESUMEN
Guillain-Barré syndrome (GBS) is the commonest post-infectious polyradiculopathy. Although genetic background of the host seems to play an important role in the susceptibility to GBS, genes conferring major risk are not yet known. Dysregulation of Toll-like receptor (TLR) molecules exacerbates immune-inflammatory responses and the genetic variations within TLR pathway-related genes contribute to differential risk to infection. The aim of this study was to delineate the impact of genetic variations within TLR2, TLR3, and TLR4 genes as well as TLR signaling pathway-related genes such as MyD88, TRIF, TRAF3, TRAF6, IRF3, NFκß1, and IκBα on risk of developing GBS. Fourteen polymorphisms located within TLR2 (rs3804099, rs111200466), TLR3 (rs3775290, rs3775291), TLR4 (rs1927911, rs11536891), MyD88 (rs7744, rs4988453), TRIF (rs8120), TRAF3 (rs12147254), TRAF6 (rs4755453), IRF3 (rs2304204), NFκß1 (rs28362491), and IκBα (rs696) genes were genotyped in 150 GBS patients and 150 healthy subjects either by PCR-RFLP or TaqMan Allelic Discrimination Assay. Genotypes of two polymorphic variants, Del/Del of rs111200466 insertion and deletion (INDEL) polymorphism of TLR2 gene and TT of rs3775290 single nucleotide polymorphism (SNP) of TLR3 gene had significantly higher frequencies among GBS patients, while the frequencies of TT genotype of rs3804099 SNP of TLR2 gene and TT genotype of rs11536891 SNP of TLR4 gene were significantly higher in controls. Gene-gene interaction study by Multifactor Dimensionality Reduction analysis also suggested a significant combined effect of TLR2, and NFκß1 genes on the risk of GBS. The SNPs in the IκBα and IRF3 genes correlated with severity of GBS. The genes encoding TLRs and TLR signaling pathway-related molecules could serve as crucial genetic markers of susceptibility and severity of GBS.
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Síndrome de Guillain-Barré , Receptor Toll-Like 2 , Receptores Toll-Like , Proteínas Adaptadoras del Transporte Vesicular/genética , Proteínas Adaptadoras del Transporte Vesicular/farmacología , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad/genética , Síndrome de Guillain-Barré/genética , Humanos , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/farmacología , Inhibidor NF-kappaB alfa/genética , Polimorfismo de Nucleótido Simple , Transducción de Señal/genética , Factor 3 Asociado a Receptor de TNF/genética , Factor 3 Asociado a Receptor de TNF/farmacología , Factor 6 Asociado a Receptor de TNF/genética , Factor 6 Asociado a Receptor de TNF/farmacología , Receptor Toll-Like 2/genética , Receptor Toll-Like 2/metabolismo , Receptor Toll-Like 3/genética , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Receptores Toll-Like/genéticaRESUMEN
Objectives: We have very little information about sexual activity and concerns of patients with myelopathy from India. The objectives of this study were to assess the sexual dysfunction and sexual concerns among patients with myelopathy due to spinal cord lesion (SCL). Materials and Methods: This study was a single-center, cross-sectional, and hospital-based study among male and female patients in the age-group 18-50 years, with disability due to myelopathy due to SCL. The data were collected using a self-designed, pretested, and semi-structured questionnaire by face-to-face interview. Results: Eighty participants were recruited in the study, of which 62 (77.5%) were men. The mean standard deviation (SD) age of the participants was 33.7 (8.6) years, and mean (SD) age at time of illness was 31.4 (8.6) years with median duration of 17 months. Among 62 males, psychogenic erection was impaired in 77.2%, reflex erection was impaired in 78.9%, and ejaculation was affected in 70.7%. Orgasm was absent or reduced in 66.1% males. Among 18 female participants, psychogenic genital arousal was reduced in 66.5%, reflex genital arousal was impaired in 55.5%, and orgasm was absent in 38.8% subjects. Sexual desire in these patients was unchanged in 41 (51.2%) and decreased or absent in 39 (48.8%). Sexual activity involvement was there in 46 (57.5%) and 34 (42.5%) had not involved in any kind of sexual activity after injury/illness. The main reasons of non-involvement in sexual activity were bladder and bowel accidents, spasticity, and difficulty in positioning. Conclusion: Comprehensive neurological rehabilitation should address sexual function of affected individual to allow them highest level of function and quality of life.
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Vanishing white matter disease (VWMD) due to eIF2B mutations is a common leukodystrophy characterised by childhood onset, autosomal recessive inheritance, and progressive clinical course with episodic worsening. There are no reports of genetically confirmed adult patients from India. We describe the phenotype of two adults with genetically confirmed VWMD and typical radiological findings. Both had spastic ataxia and cognitive and behavioural disturbances. Other neurological features included myoclonic jerks and parkinsonism. At the last follow-up (duration: 2-9 years), one patient was wheelchair-bound. VWMD is rare in adults but should be suspected based on radiological findings and confirmed by eIF2B mutation.
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Enfermedades Desmielinizantes , Factor 2B Eucariótico de Iniciación , Leucoencefalopatías , Enfermedades Neurodegenerativas , Factor 2B Eucariótico de Iniciación/genética , Humanos , Leucoencefalopatías/diagnóstico por imagen , Leucoencefalopatías/genética , Mutación/genética , FenotipoRESUMEN
Mitochondrial disorders are often difficult to diagnose because of diverse clinical phenotypes. FGF-21 and GDF-15 are metabolic hormones and promising biomarkers for the diagnosis of these disorders. This study has systematically evaluated serum FGF-21 and GDF-15 levels by ELISA in a well-defined cohort of patients with definite mitochondrial disorders (n = 30), neuromuscular disease controls (n = 36) and healthy controls (n = 36) and aimed to ascertain their utility in the diagnosis of mitochondrial disorders. Both serum FGF-21 and GDF-15 were significantly elevated in patients with mitochondrial disorders, especially in those with muscle involvement. The levels were higher in patients with mitochondrial deletions (both single and multiple) and translation disorders compared to respiratory chain subunit or assembly factor defects.
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Factores de Crecimiento de Fibroblastos/metabolismo , Marcadores Genéticos , Factor 15 de Diferenciación de Crecimiento/metabolismo , Enfermedades Mitocondriales/genética , Adolescente , Adulto , Estudios de Casos y Controles , Niño , Preescolar , Estudios Transversales , Femenino , Factores de Crecimiento de Fibroblastos/genética , Regulación de la Expresión Génica , Predisposición Genética a la Enfermedad , Factor 15 de Diferenciación de Crecimiento/genética , Humanos , Lactante , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: NMDA receptor encephalitis (NMDARE) is the most prevalent autoimmune encephalitis and it encompasses a spectrum of clinical features. It is most commonly associated with alteration in consciousness, seizures, neuro-psychiatric symptoms, and movement disorders. Electroencephalography (EEG) plays a vital role and can give clues to diagnosis in a subset of patients. METHODS: We retrospectively characterized the clinical and EEG findings in our NMDARE patients (n = 48). A total of 131 EEGs were analyzed. RESULTS: We observed that patients with seizures had a younger age of onset (p < 0.001). The most common EEG pattern that was noted was diffuse slowing (n = 20) followed by generalized rhythmic delta activity (n = 9), focal spikes and slowing (n = 8 each). Delta brush pattern was seen in only 3 EEGs. Focal ictal rhythms were seen in 3 EEGs. There was no significant difference in outcomes such as seizure recurrence, modified Rankin score (mRS) at follow up/discharge or relapse between groups of patients who had EEG abnormalities in the first EEG and with those who did not. CONCLUSIONS: NMDARE has varied EEG findings, most of them being non-specific. When combined with clinical presentation, EEG is a useful tool in the diagnosis and management of NMDARE.
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Vogt-Koyanagi-Harada (VKH) syndrome is an immune-mediated granulomatous disease which affects melanin-rich organs like eyes, skin, nervous system, and ears. Neurological and auditory manifestations usually precede the involvement of other sites. Patients may manifest with "complete" or "incomplete" syndrome. We report two patients who presented with acute headache and impaired vision. Fundus examination revealed optic disc hyperemia and exudative retinal detachment which provided a clue for the diagnosis at the bedside. Fundus fluorescein angiogram (FFA) revealed abnormal dye leakage, whereas B scan showed choroid thickening. Cerebrospinal fluid (CSF) pleocytosis contrasted with unremarkable brain magnetic resonance imaging and lack of meningeal signs. Melanophagocytosis was evidenced by melanin-laden macrophages in CSF and skin biopsy. This finding is specific for VKH syndrome and helps to clinch the diagnosis even when the complete syndrome is not present cross-sectionally. VKH syndrome should be suspected in patients with aseptic meningitis if tests for common infectious and immune-mediated diseases are negative.
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Whole exome sequencing (WES), analyzed with GENESIS and WeGET, revealed a homozygous deletion in the C1QBP gene in a patient with progressive external ophthalmoplegia (PEO) and multiple mtDNA deletions. The gene encodes the mitochondria-located complementary 1 Q subcomponent-binding protein, involved in mitochondrial homeostasis. Biallelic mutations in C1QBP cause mitochondrial cardiomyopathy and/or PEO with variable age of onset. Our patient showed only late-onset PEO-plus syndrome without overt cardiac involvement. Available data suggest that early-onset cardiomyopathy variants localize in important structural domains and PEO-plus variants in the coiled-coil region. Our patient demonstrates that C1QBP mutations should be considered in individuals with PEO with or without cardiomyopathy.
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Proteínas Portadoras/genética , Secuenciación del Exoma , Proteínas Mitocondriales/genética , Oftalmoplejía Externa Progresiva Crónica/genética , Adulto , ADN Mitocondrial/genética , Femenino , Homocigoto , Humanos , Mitocondrias/genética , Mutación , Eliminación de SecuenciaRESUMEN
BACKGROUND: The clinical spectrum of contactin-associated protein-like 2 (CASPR2) antibody-associated disease is wide and includes Morvan syndrome. Studies describing treatment and long-term outcome are limited. AIMS: We report the clinical profile and emphasize response to treatment and long-term outcome in eight patients with CASPR2-antibody-associated disease. METHODS: Clinical, radiological, electrophysiological, treatment, follow-up, and outcome data were collected by retrospective chart review. RESULTS: Clinical manifestations included Morvan syndrome (n = 7) and limbic encephalitis (n = 1). None of the patients were positive for LGI1 antibody. Associated features included myasthenia (n = 1), thymoma (n = 1), and dermatological manifestations (n = 4). Patients were treated with intravenous methylprednisolone and plasma exchange during the acute symptomatic phase followed by pulsed intravenous methyl prednisolone to maintain remission. Mean-modified Rankin score at admission (pre-treatment), discharge, and last follow-up were 3.75, 2.5, and 0.42, respectively. One patient with underlying thymoma and myasthenic crisis died. The other seven patients were followed up for a mean duration of 19.71 months. All of them improved completely. Relapse occurred in one patient after 13 months but responded favorably to steroids. CONCLUSION: CASPR2 antibody-associated disease has favorable response to immunotherapy with complete improvement and good outcome. Underlying malignancy may be a marker for poor prognosis.